Oral Druggable Space beyond the Rule of 5: Insights from Drugs and Clinical Candidates

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings 1PII of original article: S0169-409X(96)00423-1. The article was originally published in Advanced Drug Delivery Reviews 23 (1997) 3–25. 1

Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00129-0 · Cited by 18,139

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings

Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (1997) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(96)00423-1 · Cited by 11,484

Molecular properties that influence the oral bioavailability of drug candidates

Veber, D. F., Johnson, S. R., Cheng, H.-Y., Smith, B. R., Ward, K. W., & Kopple, K. D. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm020017n · Cited by 8,420

Lead- and drug-like compounds: the rule-of-five revolution

Lipinski, C. A. (2004) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2004.11.007 · Cited by 6,455

Escape from Flatland: Increasing Saturation as an Approach to Improving Clinical Success

Lovering, F., Bikker, J. A., & Humblet, C. C. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm901241e · Cited by 4,614

Can the pharmaceutical industry reduce attrition rates?

Kola, I., & Landis, J. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1470 · Cited by 4,167

Drug-like properties and the causes of poor solubility and poor permeability

Lipinski, C. A. (2000) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/s1056-8719(00)00107-6 · Cited by 3,776

How to improve R&D productivity: the pharmaceutical industry's grand challenge

Paul, S. M., Mytelka, D. S., Dunwiddie, C. T., Persinger, C. C., Munos, B. H., Lindborg, S. R., & Schacht, A. L. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3078 · Cited by 3,566

Membrane transporters in drug development

The International Transporter Consortium, Giacomini, K. M., Huang, S.-M., Tweedie, D. J., Benet, L. Z., Brouwer, K. L. R., Chu, X., Dahlin, A., Evers, R., Fischer, V., et al. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3028 · Cited by 3,340

Fast Calculation of Molecular Polar Surface Area as a Sum of Fragment-Based Contributions and Its Application to the Prediction of Drug Transport Properties

Ertl, P., Rohde, B., & Selzer, P. M. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm000942e · Cited by 3,149

Target-Oriented and Diversity-Oriented Organic Synthesis in Drug Discovery

Schreiber, S. L. (2000) · Science · doi:10.1126/science.287.5460.1964 · Cited by 2,571

Clinical development success rates for investigational drugs

Hay, M., Thomas, D. W., Craighead, J. L., Economides, C., & Rosenthal, J. (2014) · Nature Biotechnology · doi:10.1038/nbt.2786 · Cited by 2,536

The influence of drug-like concepts on decision-making in medicinal chemistry

Leeson, P. D., & Springthorpe, B. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2445 · Cited by 2,403

Quantifying the chemical beauty of drugs

Bickerton, G. R., Paolini, G. V., Besnard, J., Mureşan, S., & Hopkins, A. L. (2012) · Nature Chemistry · doi:10.1038/nchem.1243 · Cited by 2,397

Drug Discovery and Natural Products: End of an Era or an Endless Frontier?

Li, J. W.-H., & Vederas, J. C. (2009) · Science · doi:10.1126/science.1168243 · Cited by 2,056

Prediction of Drug Absorption Using Multivariate Statistics

Egan, W. J., Merz, K. M., & Baldwin, J. J. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm000292e · Cited by 2,051

Diagnosing the decline in pharmaceutical R&D efficiency

Scannell, J. W., Blanckley, A., Boldon, H., & Warrington, B. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3681 · Cited by 1,981

A Medicinal Chemist’s Guide to Molecular Interactions

Bissantz, C., Kuhn, B., & Ståhl, M. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm100112j · Cited by 1,810

Cremophor EL

Gelderblom, H. A. J., Verweij, J., Nooter, K., & Sparreboom, A. (2001) · European Journal of Cancer · doi:10.1016/s0959-8049(01)00171-x · Cited by 1,659

Caco-2 monolayers in experimental and theoretical predictions of drug transport1PII of original article: S0169-409X(96)00415-2. The article was originally published in Advanced Drug Delivery Reviews 22 (1996) 67–84.1

Artursson, P., Palm, K., & Luthman, K. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00128-9 · Cited by 1,574

Enumeration of 166 Billion Organic Small Molecules in the Chemical Universe Database GDB-17

Ruddigkeit, L., van Deursen, R., Blum, L. C., & Reymond, J.-L. (2012) · Journal of Chemical Information and Modeling · doi:10.1021/ci300415d · Cited by 1,505

Escape from Flatland 2: complexity and promiscuity

Lovering, F. (2012) · MedChemComm · doi:10.1039/c2md20347b · Cited by 1,469

The exploration of macrocycles for drug discovery — an underexploited structural class

Driggers, E. M., Hale, S. P., Lee, J., & Terrett, N. K. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2590 · Cited by 1,389

Physicochemical High Throughput Screening: Parallel Artificial Membrane Permeation Assay in the Description of Passive Absorption Processes

Kansy, M., Senner, F., & Gubernator, K. (1998) · Journal of Medicinal Chemistry · doi:10.1021/jm970530e · Cited by 1,304

A COMPARISON OF TACROLIMUS (FK506) AND CYCLOSPORINE FOR IMMUNOSUPPRESSION AFTER CADAVERIC RENAL TRANSPLANTATION1

Pirsch, J. D., Miller, J., Deierhoi, M. H., Vincenti, F. G., & Filo, R. S. (1997) · Transplantation · doi:10.1097/00007890-199704150-00013 · Cited by 1,120

Role of P-Glycoprotein in Pharmacokinetics

Lin, J. H., & Yamazaki, M. (2003) · Clinical Pharmacokinetics · doi:10.2165/00003088-200342010-00003 · Cited by 1,023

Generation of a Set of Simple, Interpretable ADMET Rules of Thumb

Gleeson, M. P. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm701122q · Cited by 996

Impact of OATP transporters on pharmacokinetics

Kalliokoski, A., & Niemi, M. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00430.x · Cited by 994

MDCK (Madin-Darby Canine Kidney) Cells: A Tool for Membrane Permeability Screening

Irvine, J. D., Takahashi, L. H., Lockhart, K., Cheong, J., Tolan, J. W., Selick, H. E., & Grove, J. R. (1999) · Journal of Pharmaceutical Sciences · doi:10.1021/js9803205 · Cited by 984

Etoposide: four decades of development of a topoisomerase II inhibitor

Hande, K. R. (1998) · European Journal of Cancer · doi:10.1016/s0959-8049(98)00228-7 · Cited by 962

Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect

Gao, M., Nettles, R. E., Belema, M., Snyder, L. B., Nguyen, V. N., Fridell, R. A., Serrano‐Wu, M. H., Langley, D. R., Sun, J.-H., O’Boyle, D. R., et al. (2010) · Nature · doi:10.1038/nature08960 · Cited by 941

An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus

Lamarre, D., Anderson, P. C., Bailey, M. D., Beaulieu, P. L., Bolger, G. T., Bonneau, P. R., Bös, M., Cameron, D. R., Cartier, M., Cordingley, M. G., et al. (2003) · Nature · doi:10.1038/nature02099 · Cited by 918

Patient preferences for oral versus intravenous palliative chemotherapy.

Liu, G., Franssen, E., Fitch, M. I., & Warner, E. (1997) · Journal of Clinical Oncology · doi:10.1200/jco.1997.15.1.110 · Cited by 917

Macrocycles Are Great Cycles: Applications, Opportunities, and Challenges of Synthetic Macrocycles in Drug Discovery

Marsault, É., & Peterson, M. L. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm1012374 · Cited by 878

Global mapping of pharmacological space

Paolini, G. V., Shapland, R. H. B., van Hoorn, W. P., Mason, J. S., & Hopkins, A. L. (2006) · Nature Biotechnology · doi:10.1038/nbt1228 · Cited by 822

Drug-Like Properties: Concepts, Structure Design and Methods from ADME to Toxicity Optimization

Kerns, E. H., & Di, L. (2016) · Cited by 784

Sirolimus: its discovery, biological properties, and mechanism of action

Sehgal, S. N. (2003) · Transplantation Proceedings · doi:10.1016/s0041-1345(03)00211-2 · Cited by 784

Polar Molecular Surface Properties Predict the Intestinal Absorption of Drugs in Humans

Palm, K., Stenberg, P., Luthman, K., & Artursson, P. (1997) · Pharmaceutical Research · doi:10.1023/a:1012188625088 · Cited by 762

Cyclodextrins

Stella, V. J., & He, Q. (2008) · Toxicologic Pathology · doi:10.1177/0192623307310945 · Cited by 730

Natural Products as Leads to Potential Drugs: An Old Process or the New Hope for Drug Discovery?

Newman, D. J. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm0704090 · Cited by 717

Role of intestinal P-glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclosporine*

Lown, K. S., Mayo, R. R., Leichtman, A. B., Hsiao, H.-L., Turgeon, D. K., Schmiedlin‐Ren, P., Brown, M. B., Guo, W.-S., Rossi, S. J., Benet, L. Z., et al. (1997) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(97)90027-8 · Cited by 679

Coexistence of passive and carrier-mediated processes in drug transport

Sugano, K., Kansy, M., Artursson, P., Avdeef, A., Bendels, S., Di, L., Ecker, G. F., Faller, B., Fischer, H., Gerebtzoff, G., et al. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3187 · Cited by 672

Calculation of Molecular Lipophilicity: State-of-the-Art and Comparison of LogP Methods on more than 96,000 Compounds

Mannhold, R., Poda, G. I., Ostermann, C., & Tetko, I. V. (2008) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21494 · Cited by 663

Comparison of Automatic Three-Dimensional Model Builders Using 639 X-ray Structures

Sadowski, J., Gasteiger, J., & Klebe, G. (1994) · Journal of Chemical Information and Computer Sciences · doi:10.1021/ci00020a039 · Cited by 645

Improving Drug Candidates by Design: A Focus on Physicochemical Properties As a Means of Improving Compound Disposition and Safety

Meanwell, N. A. (2011) · Chemical Research in Toxicology · doi:10.1021/tx200211v · Cited by 639

Estimation of the size of drug-like chemical space based on GDB-17 data

Polishchuk, P. G., Madzhidov, T. I., & Varnek, A. (2013) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-013-9672-4 · Cited by 619

Intramolecular Hydrogen Bonding in Medicinal Chemistry

Kuhn, B., Mohr, P., & Ståhl, M. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm100087s · Cited by 581

Macrocyclic Drugs and Clinical Candidates: What Can Medicinal Chemists Learn from Their Properties?

Giordanetto, F., & Kihlberg, J. O. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400887j · Cited by 577

Clinical Pharmacokinetics of Everolimus

Kirchner, G. I., Meier-Wiedenbach, I., & Manns, M. P. (2004) · Clinical Pharmacokinetics · doi:10.2165/00003088-200443020-00002 · Cited by 510

Defining Desirable Central Nervous System Drug Space through the Alignment of Molecular Properties, in Vitro ADME, and Safety Attributes

Wager, T. T., Chandrasekaran, R. Y., Hou, X., Troutman, M. D., Verhoest, P. R., Villalobos, A., & Will, Y. (2010) · ACS Chemical Neuroscience · doi:10.1021/cn100007x · Cited by 503

Molecular Shape Diversity of Combinatorial Libraries: A Prerequisite for Broad Bioactivity

Sauer, W., & Schwarz, M. K. (2003) · Journal of Chemical Information and Computer Sciences · doi:10.1021/ci025599w · Cited by 500

Clinical Pharmacokinetics of Cyclosporin

Ptachcinski, R. J., Venkataramanan, R., & Burckart, G. J. (1986) · Clinical Pharmacokinetics · doi:10.2165/00003088-198611020-00002 · Cited by 497

Testing the Conformational Hypothesis of Passive Membrane Permeability Using Synthetic Cyclic Peptide Diastereomers

Rezai, T., Yu, B., Millhauser, G. L., Jacobson, M. P., & Lokey, R. S. (2006) · Journal of the American Chemical Society · doi:10.1021/ja0563455 · Cited by 494

Macrocycles In New Drug Discovery

Mallinson, J., & Collins, I. (2012) · Future Medicinal Chemistry · doi:10.4155/fmc.12.93 · Cited by 488

History of the development of azole derivatives

Maertens, J. A. (2004) · Clinical Microbiology and Infection · doi:10.1111/j.1470-9465.2004.00841.x · Cited by 487

Ritonavir

Hsu, A., Granneman, G. R., & Bertz, R. (1998) · Clinical Pharmacokinetics · doi:10.2165/00003088-199835040-00002 · Cited by 486

Can we rationally design promiscuous drugs?

HOPKINS, A., MASON, J., & OVERINGTON, J. (2006) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2006.01.013 · Cited by 469

Knowledge-Based, Central Nervous System (CNS) Lead Selection and Lead Optimization for CNS Drug Discovery

Ghose, A. K., Herbertz, T., Hudkins, R. L., Dorsey, B. D., & Mallamo, J. P. (2011) · ACS Chemical Neuroscience · doi:10.1021/cn200100h · Cited by 463

Endogenous and exogenous cardiac glycosides: their roles in hypertension, salt metabolism, and cell growth

Schöner, W., & Scheiner‐Bobis, G. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00098.2007 · Cited by 458

Pharmacokinetic/Pharmacodynamic Profile of Posaconazole

Li, Y., Theuretzbacher, U., Clancy, C. J., Nguyen, M. H., & Derendorf, H. (2010) · Clinical Pharmacokinetics · doi:10.2165/11319340-000000000-00000 · Cited by 452

Absorption and Drug Development: Solubility, Permeability, and Charge State

Avdeef, A. (2003) · Cited by 451

Diversity-oriented synthesis: producing chemical tools for dissecting biology

Connor, C. J. O., Beckmann, H. S. G., & Spring, D. R. (2012) · Chemical Society Reviews · doi:10.1039/c2cs35023h · Cited by 438

mTOR signaling and drug development in cancer

Dancey, J. E. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.21 · Cited by 426

Drug discovery beyond the ‘rule-of-five’

Zhang, M., & Wilkinson, B. (2007) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2007.10.005 · Cited by 421

Conformational Flexibility, Internal Hydrogen Bonding, and Passive Membrane Permeability: Successful in Silico Prediction of the Relative Permeabilities of Cyclic Peptides

Rezai, T., Bock, J. E., Zhou, M. V., Kalyanaraman, C., Lokey, R. S., & Jacobson, M. P. (2006) · Journal of the American Chemical Society · doi:10.1021/ja063076p · Cited by 421

Finding the sweet spot: the role of nature and nurture in medicinal chemistry

Hann, M. M., & Keserű, G. M. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3701 · Cited by 418

Using the Golden Triangle to optimize clearance and oral absorption

Johnson, T. W., Dress, K. R., & Edwards, M. P. (2009) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2009.08.045 · Cited by 399

On-resin N-methylation of cyclic peptides for discovery of orally bioavailable scaffolds

White, T. R., Renzelman, C. M., Rand, A. C., Rezai, T., McEwen, C. M., Gelev, V., Turner, R. A., Linington, R. G., Leung, S. S. F., Kalgutkar, A. S. S., et al. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.664 · Cited by 394

CMX001 to Prevent Cytomegalovirus Disease in Hematopoietic-Cell Transplantation

Marty, F. M., Winston, D. J., Rowley, S. D., Vance, E. A., Papanicolaou, G. A., Mullane, K. M., Brundage, T. M., Robertson, A. T., Godkin, S., Momméja-Marin, H., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1303688 · Cited by 373

Drug Transporters in Drug Efficacy and Toxicity

DeGorter, M. K., Xia, C. Q., Yang, J. J., & Kim, R. B. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134529 · Cited by 372

Cyclosporin Clinical Pharmacokinetics

Fahr, A. (1993) · Clinical Pharmacokinetics · doi:10.2165/00003088-199324060-00004 · Cited by 357

The p K BHX Database: Toward a Better Understanding of Hydrogen-Bond Basicity for Medicinal Chemists

Laurence, C., Brameld, K. A., Graton, J., Questel, J. L., & Renault, É. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm801331y · Cited by 353

Defining optimum lipophilicity and molecular weight ranges for drug candidates—Molecular weight dependent lower logD limits based on permeability

Waring, M. J. (2009) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2009.03.109 · Cited by 340

Intramolecular hydrogen bonding to improve membrane permeability and absorption in beyond rule of five chemical space

Alex, A., Millan, D. S., Perez, M., Wakenhut, F., & Whitlock, G. A. (2011) · MedChemComm · doi:10.1039/c1md00093d · Cited by 338

Comparative Pharmacokinetics and Pharmacodynamics of the Rifamycin Antibacterials

Burman, W. J., Gallicano, K., & Peloquin, C. A. (2001) · Clinical Pharmacokinetics · doi:10.2165/00003088-200140050-00002 · Cited by 338

Going further than Lipinski's rule in drug design

Walters, W. P. (2012) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2012.648612 · Cited by 322

History of the Development of Rifampin

Sensi, P. (1983) · Clinical Infectious Diseases · doi:10.1093/clinids/5.supplement_3.s402 · Cited by 318

Prediction of Human Intestinal First-Pass Metabolism of 25 CYP3A Substrates from In Vitro Clearance and Permeability Data

Gertz, M., Harrison, A., Houston, J., & Galetin, A. (2010) · Drug Metabolism And Disposition · doi:10.1124/dmd.110.032649 · Cited by 317

Biopharmaceutical challenges associated with drugs with low aqueous solubility—The potential impact of lipid-based formulations

O’Driscoll, C. M., & Griffin, B. T. (2007) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2007.10.012 · Cited by 304

Review of Macrolides and Ketolides

Zhanel, G. G., Dueck, M., Hoban, D. J., Vercaigne, L. M., Embil, J. M., Gin, A. S., & Karlowsky, J. A. (2001) · Drugs · doi:10.2165/00003495-200161040-00003 · Cited by 300

Discovery of Ledipasvir (GS-5885): A Potent, Once-Daily Oral NS5A Inhibitor for the Treatment of Hepatitis C Virus Infection

Link, J. O., Taylor, J. G., Xu, L., Mitchell, M. L., Guo, H., Liu, H., Kato, D., Kirschberg, T. A., Sun, J., Squires, N., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm401499g · Cited by 300

Pharmacokinetics, Safety, and Tolerability of Oral Posaconazole Administered in Single and Multiple Doses in Healthy Adults

Courtney, R., Pai, S. M., Laughlin, M. A., Lim, J. M., & Batra, V. K. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.9.2788-2795.2003 · Cited by 298

Stochastic Voyages into Uncharted Chemical Space Produce a Representative Library of All Possible Drug-Like Compounds

Virshup, A. M., Contreras-García, J., Wipf, P., Yang, W., & Beratan, D. N. (2013) · Journal of the American Chemical Society · doi:10.1021/ja401184g · Cited by 294

Caco-2 monolayers in experimental and theoretical predictions of drug transport

Artursson, P., Palm, K., & Luthman, K. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.09.005 · Cited by 291

IN VITRO INHIBITION OF UDP GLUCURONOSYLTRANSFERASES BY ATAZANAVIR AND OTHER HIV PROTEASE INHIBITORS AND THE RELATIONSHIP OF THIS PROPERTY TO IN VIVO BILIRUBIN GLUCURONIDATION

Zhang, D., Chando, T. J., Everett, D. W., Patten, C., Dehal, S. S., & Humphreys, W. G. (2005) · Drug Metabolism and Disposition · doi:10.1124/dmd.105.005447 · Cited by 288

Posaconazole: a broad-spectrum triazole antifungal

Torres, H. A., Hachem, R. Y., Chemaly, R. F., Kontoyiannis, D. P., & RAAD, I. I. (2005) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(05)70297-8 · Cited by 287

Characterization of the interaction of 2‐hydroxypropyl‐β‐cyclodextrin with itraconazole at pH 2, 4, and 7

Peeters, J., Neeskens, P., Tollenaere, J. P., Remoortere, P. V., & Brewster, M. E. (2002) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.10126 · Cited by 272

Oral cancer treatment: developments in chemotherapy and beyond

O'Neill, V. J., & Twelves, C. J. (2002) · British Journal of Cancer · doi:10.1038/sj.bjc.6600591 · Cited by 270

Getting pharmaceutical R&D back on target

Bunnage, M. E. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.581 · Cited by 269

MK-5172, a Selective Inhibitor of Hepatitis C Virus NS3/4a Protease with Broad Activity across Genotypes and Resistant Variants

Summa, V., Ludmerer, S. W., McCauley, J. A., Fandozzi, C. M., Burlein, C., Giuliano, C., Coleman, P. J., DiMuzio, J. M., Ferrara, M., Filippo, M. D., et al. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00324-12 · Cited by 260

Current industrial practices of assessing permeability and P-glycoprotein interaction

Balimane, P. V., Han, Y., & Chong, S. (2006) · The AAPS Journal · doi:10.1208/aapsj080101 · Cited by 254

Penetration of Anti-Infective Agents into Pulmonary Epithelial Lining Fluid

Rodvold, K. A., George, J. M., & Yoo, L. (2011) · Clinical Pharmacokinetics · doi:10.2165/11594090-000000000-00000 · Cited by 247

Macrocyclic Drugs and Synthetic Methodologies toward Macrocycles

Yu, X., & Sun, D. (2013) · Molecules · doi:10.3390/molecules18066230 · Cited by 236

Structural Modifications that Alter the P-Glycoprotein Efflux Properties of Compounds

Hitchcock, S. A. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm201136z · Cited by 232

Structural Biology and Drug Discovery of Difficult Targets: The Limits of Ligandability

Surade, S., & Blundell, T. L. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2011.12.013 · Cited by 230

P-Glycoprotein Limits the Brain Penetration of Nonsedating but not Sedating H1-Antagonists

Chen, C., Hanson, E., Watson, J. W., & Lee, J. S. (2003) · Drug Metabolism and Disposition · doi:10.1124/dmd.31.3.312 · Cited by 227

Paclitaxel (Taxol®): A success story with valuable lessons for natural product drug discovery and development

Cragg, G. M. L. (1998) · Medicinal Research Reviews · doi:10.1002/(sici)1098-1128(199809)18:5 · Cited by 217

mRNA display: from basic principles to macrocycle drug discovery

Josephson, K., Ricardo, A., & Szostak, J. W. (2013) · Drug Discovery Today · doi:10.1016/j.drudis.2013.10.011 · Cited by 216

Discovery and Development of Simeprevir (TMC435), a HCV NS3/4A Protease Inhibitor

Rosenquist, Å., Samuelsson, B., Johansson, P.-O., Cummings, M. D., Lenz, O., Raboisson, P., Simmen, K., Vendeville, S., de Kock, H., Nilsson, M., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm401507s · Cited by 215

Solvent-dependent conformation and hydrogen-bonding capacity of cyclosporin A: evidence from partition coefficients and molecular dynamics simulations

Tayar, N. E., Mark, A. E., Vallat, P., Brunne, R. M., Testa, B., & A, W. F. V. G. (1993) · Journal of Medicinal Chemistry · doi:10.1021/jm00076a002 · Cited by 215

An overview of FDA-approved new molecular entities: 1827–2013

Kinch, M. S., Haynesworth, A., Kinch, S. L., & Hoyer, D. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.03.018 · Cited by 210

Macrolide antibiotics : chemistry, biology, and practice

大村, 智. (2002) · Academic Press eBooks · Cited by 207

The Influence of Macrolide Antibiotics on the Uptake of Organic Anions and Drugs Mediated by OATP1B1 and OATP1B3

Seithel‐Keuth, A., Eberl, S., Singer, K., Auge, D., Heinkele, G., Wolf, N. B., Dörje, F., Fromm, M. F., & König, J. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.106.014407 · Cited by 207

Coadministration of oral cyclosporin A enables oral therapy with paclitaxel.

Terwogt, J. M. M., Malingré, M. M., Beijnen, J. H., Huinink, W. W. T. B., Rosing, H., Koopman, F. J., van Tellingen, O., Swart, M., & Schellens, J. H. M. (1999) · PubMed · Cited by 205

Discovery of MK‐8742: An HCV NS5A Inhibitor with Broad Genotype Activity

Coburn, C. A., Meinke, P. T., Chang, W., Fandozzi, C. M., Graham, D. J., Hu, B., Huang, Q., Kargman, S., Kozlowski, J. A., Liu, R., et al. (2013) · ChemMedChem · doi:10.1002/cmdc.201300343 · Cited by 202

Determinants and associated factors influencing medication adherence and persistence to oral anticancer drugs: A systematic review

Verbrugghe, M., Verhaeghe, S., Lauwaert, K., Beeckman, D., & Van Hecke, A. (2013) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2012.12.014 · Cited by 202

Form and Function in Cyclic Peptide Natural Products: A Pharmacokinetic Perspective

Bockus, A. T., McEwen, C. M., & Lokey, R. S. (2013) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026611313070005 · Cited by 200

Cobicistat (GS-9350): A Potent and Selective Inhibitor of Human CYP3A as a Novel Pharmacoenhancer

Xu, L., Liu, H., Murray, B. P., Callebaut, C., Lee, M. S., Hong, A. Y., Strickley, R. G., Tsai, L. K., Stray, K. M., Wang, Y., et al. (2010) · ACS Medicinal Chemistry Letters · doi:10.1021/ml1000257 · Cited by 197

Novel therapies for hepatitis C — one pill fits all?

Manns, M. P., & von Hahn, T. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4050 · Cited by 194

Absorption of montelukast is transporter mediated: a common variant of OATP2B1 is associated with reduced plasma concentrations and poor response

Mougey, E. B., Feng, H., Castro, M., Irvin, C. G., & Lima, J. J. (2009) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e32831bd98c · Cited by 191

Preclinical Profile and Characterization of the Hepatitis C Virus NS3 Protease Inhibitor Asunaprevir (BMS-650032)

McPhee, F., Sheaffer, A. K., Friborg, J., Hernandez, D., Falk, P. J., Zhai, G., Levine, S., Chaniewski, S., Yu, F., Barry, D., et al. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01186-12 · Cited by 190

Intestinal Permeability of Cyclic Peptides: Common Key Backbone Motifs Identified

Beck, J. G., Chatterjee, J., Laufer, B., Marelli, U. K., Frank, A. O., Neubauer, S., Ovadia, O., Greenberg, S., Gilon, C., Hoffman, A., et al. (2012) · Journal of the American Chemical Society · doi:10.1021/ja303200d · Cited by 189

Forecasting the Oral Absorption Behavior of Poorly Soluble Weak Bases Using Solubility and Dissolution Studies in Biorelevant Media

Kostewicz, E. S., Brauns, U., Becker, R., & Dressman, J. (2002) · Pharmaceutical Research · doi:10.1023/a:1014407421366 · Cited by 182

Update on rifampin, rifabutin, and rifapentine drug interactions

Baciewicz, A. M., Chrisman, C. R., Finch, C. K., & Self, T. H. (2012) · Current Medical Research and Opinion · doi:10.1185/03007995.2012.747952 · Cited by 178

Esterification of cidofovir with alkoxyalkanols increases oral bioavailability and diminishes drug accumulation in kidney

Ciesla, S. L., Trahan, J., Wan, W., Beadle, J. R., Aldern, K. A., Painter, G. R., & Hostetler, K. Y. (2003) · Antiviral Research · doi:10.1016/s0166-3542(03)00110-4 · Cited by 177

Formulating Poorly Water Soluble Drugs

Williams, R. O., Miller, D. A., & Watts, A. B. (2011) · AAPS advances in the pharmaceutical sciences series · doi:10.1007/978-1-4614-1144-4 · Cited by 177

Evidence for a Polarized Efflux System in Caco-2 Cells Capable of Modulating Cyclosporine A Transport

Augustijns, P., Bradshaw, T., Gan, L., Hendren, R. W., & Thakker, D. R. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.2487 · Cited by 172

The road map to oral bioavailability: an industrial perspective

Thomas, V. H., Bhattachar, S., Hitchingham, L., Zocharski, P., Naath, M., Surendran, N., Stoner, C. L., & El‐Kattan, A. F. (2006) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2.4.591 · Cited by 169

Discovery of a Thieno[2,3- d ]pyrimidine-2,4-dione Bearing a p -Methoxyureidophenyl Moiety at the 6-Position: A Highly Potent and Orally Bioavailable Non-Peptide Antagonist for the Human Luteinizing Hormone-Releasing Hormone Receptor

Sasaki, S., Cho, N., Nara, Y., Harada, M., Endo, S., Suzuki, N., Furuya, S., & Fujino, M. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm020180i · Cited by 162

Solid-state characterization of rifampicin samples and its biopharmaceutic relevance

Agrawal, S., Ashokraj, Y., Bharatam, P. V., Pillai, O., & Panchagnula, R. (2004) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2004.02.011 · Cited by 162

Clinical Pharmacokinetics and Summary of Efficacy and Tolerability of Atazanavir

Tiec, C. L., Barrail, A., Goujard, C. C., & Taburet, A. (2005) · Clinical Pharmacokinetics · doi:10.2165/00003088-200544100-00003 · Cited by 159

Modulation of P-glycoprotein function in human lymphocytes and Caco-2 cell monolayers by HIV-1 protease inhibitors

Profit, L., Eagling, V. A., & Back, D. J. (1999) · AIDS · doi:10.1097/00002030-199909100-00004 · Cited by 158

Drug–Drug Interactions Between HMG-CoA Reductase Inhibitors (Statins) and Antiviral Protease Inhibitors

Chauvin, B., Drouot, S., Barrail‐Tran, A., & Taburet, A. (2013) · Clinical Pharmacokinetics · doi:10.1007/s40262-013-0075-4 · Cited by 156

Interaction of HIV protease inhibitors with OATP1B1, 1B3, and 2B1

Annaert, P., Ye, Z., Stieger, B., & Augustijns, P. (2010) · Xenobiotica · doi:10.3109/00498250903509375 · Cited by 156

Physicochemical drug properties associated within vivotoxicological outcomes: a review

Price, D. A., Blagg, J., Jones, L. H., Greene, N., & Wager, T. T. (2009) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425250903042318 · Cited by 155

Cellular Uptake and Efflux of Azithromycin, Erythromycin, Clarithromycin, Telithromycin, and Cethromycin

Bosnar, M., Kelnerić, Ž., Kos, V. M., Haber, V. E., & Parnham, M. J. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.6.2372-2377.2005 · Cited by 152

High lipophilicity decreases drug transport across intestinal epithelial cells.

Wils, P., Warnery, A., Phung-Ba, V., Legrain, S., & Scherman, D. (1994) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)38749-5 · Cited by 149

Validation and application of Caco-2 assays for the in vitro evaluation of development candidate drugs as substrates or inhibitors of P-glycoprotein to support regulatory submissions

Elsby, R., Surry, D. D., Smith, V., & Gray, A. J. (2008) · Xenobiotica · doi:10.1080/00498250802050880 · Cited by 144

Making sense of itraconazole pharmacokinetics

Prentice, A. G., & Glasmacher, A. G. (2005) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dki220 · Cited by 143

How hydrogen bonds impact P-glycoprotein transport and permeability

Desai, P. V., Raub, T. J., & Blanco, M.-J. (2012) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2012.08.059 · Cited by 141

Pharmacokinetics of oral and intravenous rifampicin during chronic administration

Loos, U., Musch, E., Jensen, J. C., Mikus, G., Schwabe, H. K., & Eichelbaum, M. F. (1985) · Journal of Molecular Medicine · doi:10.1007/bf01733779 · Cited by 141

Discovery of Danoprevir (ITMN-191/R7227), a Highly Selective and Potent Inhibitor of Hepatitis C Virus (HCV) NS3/4A Protease

Jiang, Y., Andrews, S. W., Condroski, K. R., Buckman, B. O., Serebryany, V., Wenglowsky, S., Kennedy, A. L., Madduru, M. R., Wang, B., Lyon, M. A., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400164c · Cited by 141

MK-7009, a Potent and Selective Inhibitor of Hepatitis C Virus NS3/4A Protease

Liverton, N. J., Carroll, S. S., DiMuzio, J. M., Fandozzi, C. M., Graham, D. J., Hazuda, D. J., Holloway, M. K., Ludmerer, S. W., McCauley, J. A., McIntyre, C. J., et al. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00677-09 · Cited by 141

In Vitro Interaction of the HIV Protease Inhibitor Ritonavir with Herbal Constituents: Changes in P-gp and CYP3A4 Activity

Patel, J., Buddha, B., Dey, S., Pal, D., & Mitra, A. K. (2004) · American Journal of Therapeutics · doi:10.1097/01.mjt.0000101827.94820.22 · Cited by 139

Beyond Size, Ionization State, and Lipophilicity: Influence of Molecular Topology on Absorption, Distribution, Metabolism, Excretion, and Toxicity for Druglike Compounds

Yang, Y., Engkvist, O., Llinàs, A., & Chen, H. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm201548z · Cited by 139

SCY-635, a Novel Nonimmunosuppressive Analog of Cyclosporine That Exhibits Potent Inhibition of Hepatitis C Virus RNA ReplicationIn Vitro

Hopkins, S., Scorneaux, B., Huang, Z., Murray, M. G., Wring, S. A., Smitley, C., Harris, R. W., Erdmann, F., Fischer, G. S., & Ribeill, Y. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00660-09 · Cited by 139

The Clinical Pharmacokinetics of Rifabutin

Blaschke, T. F., & Skinner, M. (1996) · Clinical Infectious Diseases · doi:10.1093/clinids/22.supplement_1.s15 · Cited by 138

Induction of Influx and Efflux Transporters and Cytochrome P450 3A4 in Primary Human Hepatocytes by Rifampin, Rifabutin, and Rifapentine

Williamson, B., Dooley, K. E., Zhang, Y., Back, D. J., & Owen, A. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01124-13 · Cited by 138

Cobicistat Boosts the Intestinal Absorption of Transport Substrates, Including HIV Protease Inhibitors and GS-7340, In Vitro

Lepist, E., Phan, T. K., Roy, A., Tong, L., Staiger, K. M., Murray, B. P., & Ray, A. S. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01089-12 · Cited by 137

Isavuconazole: A Comprehensive Review of Spectrum of Activity of a New Triazole

Thompson, G. R., & Wiederhold, N. P. (2010) · Mycopathologia · doi:10.1007/s11046-010-9324-3 · Cited by 134

ATAZANAVIR: EFFECTS ON P-GLYCOPROTEIN TRANSPORT AND CYP3A METABOLISM IN VITRO

Perloff, E. S., Duan, S. X., Skolnik, P. R., Greenblatt, D. J., & Moltke, L. L. (2005) · Drug Metabolism and Disposition · doi:10.1124/dmd.104.002931 · Cited by 134

Optimizing PK properties of cyclic peptides: the effect of side chain substitutions on permeability and clearance

Rand, A. C., Leung, S. S. F., Eng, H. F., Rotter, C. J., Sharma, R., Kalgutkar, A. S. S., Zhang, Y., Varma, M. V. S., Farley, K. A., Khunte, B., et al. (2012) · MedChemComm · doi:10.1039/c2md20203d · Cited by 132

2012 FDA drug approvals

Mullard, A. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd3946 · Cited by 132

Discovery of ABT-267, a Pan-Genotypic Inhibitor of HCV NS5A

DeGoey, D. A., Randolph, J. T., Liu, D., Pratt, J. K., Hutchins, C. W., Donner, P., Krueger, A. C., Matulenko, M. A., Patel, S. V., Motter, C. E., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm401398x · Cited by 131

Active Apical Secretory Efflux of the HIV Protease Inhibitors Saquinavir and Ritonavir in Caco-2 Cell Monolayers

Alsenz, J., Steffen, H., & Alex, R. (1998) · Pharmaceutical Research · doi:10.1023/a:1011924314899 · Cited by 130

Ivermectin: uses and impact 20 years on

Fox, L. M. (2006) · Current Opinion in Infectious Diseases · doi:10.1097/qco.0b013e328010774c · Cited by 127

Targeting Intestinal Transporters for Optimizing Oral Drug Absorption

Varma, M. V. S., Ambler, C. M., Ullah, M., Rotter, C. J., Sun, H., Litchfield, J., Fenner, K. S., & El‐Kattan, A. F. (2010) · Current Drug Metabolism · doi:10.2174/138920010794328850 · Cited by 127

Transport and epithelial secretion of the cardiac glycoside, digoxin, by human intestinal epithelial (Caco‐2) cells

Cavet, M. E., West, M., & Simmons, N. L. (1996) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1996.tb15550.x · Cited by 124

The Influence of Target Family and Functional Activity on the Physicochemical Properties of Pre-Clinical Compounds

Morphy, R. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm0512185 · Cited by 123

Chrysotherapy: a synoptic review

Eisler, R. (2003) · Inflammation Research · doi:10.1007/s00011-003-1208-2 · Cited by 122

Drug discovery in the next decade: innovation needed ASAP

Bennani, Y. L. (2011) · Drug Discovery Today · doi:10.1016/j.drudis.2011.06.004 · Cited by 120

Everolimus: A Proliferation Signal Inhibitor with Clinical Applications in Organ Transplantation, Oncology, and Cardiology

Gabardi, S., & Baroletti, S. A. (2010) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.30.10.1044 · Cited by 119

High Throughput Method for the Indirect Detection of Intramolecular Hydrogen Bonding

Goetz, G. H., Farrell, W. P., Shalaeva, M. Y., Sciabola, S., Anderson, D. P., Yan, J., Philippe, L., & Shapiro, M. J. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm401859b · Cited by 119

Predicting and Improving the Membrane Permeability of Peptidic Small Molecules

Rafi, S. B., Hearn, B. R., Vedantham, P., Jacobson, M. P., & Renslo, A. R. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm201634q · Cited by 117

Use of 3D Properties to Characterize Beyond Rule-of-5 Property Space for Passive Permeation

Guimarães, C. R. W., Mathiowetz, A. M., Shalaeva, M. Y., Goetz, G. H., & Liras, S. I. (2012) · Journal of Chemical Information and Modeling · doi:10.1021/ci300010y · Cited by 117

The Discovery of Asunaprevir (BMS-650032), An Orally Efficacious NS3 Protease Inhibitor for the Treatment of Hepatitis C Virus Infection

Scola, P. M., Sun, L., Wang, A. X., Chen, J., Sin, N., Venables, B. L., Sit, S., Chen, Y., Cocuzza, A. J., Bilder, D. M., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500297k · Cited by 116

BCRP Transports Dipyridamole and is Inhibited by Calcium Channel Blockers

Zhang, Y., Gupta, A., Wang, H., Zhou, L., Vethanayagam, R. R., Unadkat, J. D., & Mao, Q. (2005) · Pharmaceutical Research · doi:10.1007/s11095-005-8384-4 · Cited by 116

Dynamic Dissolution Testing To Establish In Vitro/In Vivo Correlations for Montelukast Sodium, a Poorly Soluble Drug

Okumu, A., Maso, M. D., & Löbenberg, R. (2008) · Pharmaceutical Research · doi:10.1007/s11095-008-9642-z · Cited by 116

Development, validation and utility of an in vitro technique for assessment of potential clinical drug–drug interactions involving P-glycoprotein

Keogh, J. P., & Kunta, J. R. (2006) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2005.11.011 · Cited by 113

Pharmacokinetics and Metabolism in Drug Design

Smith, D. A., Waterbeemd, H. V. D. 1., & Walker, D. K. (2003) · European Journal of Medicinal Chemistry · doi:10.1016/s0223-5234(03)00124-7 · Cited by 112

Impact of CYP3A5 and MDR1(ABCB1) C3435T Polymorphisms on the Pharmacokinetics of Tacrolimus in Renal Transplant Recipients

Tada, H., Tsuchiya, N., Satoh, S., Kagaya, H., Li, Z., Sato, K., Miura, M., Suzuki, T., Kato, T., & Habuchi, T. (2005) · Transplantation Proceedings · doi:10.1016/j.transproceed.2005.02.073 · Cited by 110

The absolute stereochemistry and conformation of avermectin B2a aglycone and avermectin B1a

Springer, J. P., Arison, B. H., Hirshfield, J. M., & Hoogsteen, K. (1981) · Journal of the American Chemical Society · doi:10.1021/ja00404a041 · Cited by 104

Dependence of Molecular Properties on Proteomic Family for Marketed Oral Drugs

Vieth, M., & Sutherland, J. J. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm0603825 · Cited by 103

Discovery of Narlaprevir (SCH 900518): A Potent, Second Generation HCV NS3 Serine Protease Inhibitor

Arasappan, A., Bennett, F., Bogen, S. L., Venkatraman, S., Blackman, M., Chen, K. X., Hendrata, S., Huang, Y., Huelgas, R. M., Nair, L., et al. (2010) · ACS Medicinal Chemistry Letters · doi:10.1021/ml9000276 · Cited by 102

Molecular properties that influence oral drug-like behavior.

Lajiness, M. S., Vieth, M., & Erickson, J. A. (2004) · PubMed · Cited by 102

Uptake of azithromycin by various cells and its intracellular activity under in vivo conditions

Wildfeuer, A., Laufen, H., & Zimmermann, T. (1996) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.40.1.75 · Cited by 101

Clinical studies with oral lipid based formulations of poorly soluble compounds.

Fatouros, D. G., Karpf, D. M., Nielsen, F. S., & Müllertz, A. (2007) · PubMed Central · Cited by 98

Integration of in Silico and in Vitro Tools for Scaffold Optimization during Drug Discovery: Predicting P-Glycoprotein Efflux

Desai, P. V., Sawada, G. A., Watson, I. A., & Raub, T. J. (2013) · Molecular Pharmaceutics · doi:10.1021/mp300555n · Cited by 98

Pharmacokinetics, safety and bioavailability of HPMPC (cidofovir) in human immunodeficiency virus-infected subjects

Wachsman, M., Petty, B. G., Cundy, K. C., Jaffe, H. S., Fisher, P., Pastelak, A. M., & Lietman, P. S. (1996) · Antiviral Research · doi:10.1016/0166-3542(95)00829-2 · Cited by 97

The relative systemic availability of ivermectin after administration as capsule, tablet, and oral solution

Edwards, G., Dingsdale, A., Helsby, N. A., Orme, M. L., & Breckenridge, A. (1988) · European Journal of Clinical Pharmacology · doi:10.1007/bf00637608 · Cited by 97

Cobicistat: A Review of Its Use as a Pharmacokinetic Enhancer of Atazanavir and Darunavir in Patients with HIV-1 Infection

Deeks, E. D. (2013) · Drugs · doi:10.1007/s40265-013-0160-x · Cited by 95

Impact of Stereospecific Intramolecular Hydrogen Bonding on Cell Permeability and Physicochemical Properties

Over, B., McCarren, P. R., Artursson, P., Foley, M. A., Giordanetto, F., Grönberg, G., Hilgendorf, C., Lee, M. D., Matsson, P., Muncipinto, G., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500059t · Cited by 90

Integrating Intramolecular Hydrogen Bonding (IMHB) Considerations in Drug Discovery Using ΔlogP As a Tool

Shalaeva, M. Y., Caron, G., Abramov, Y. A., O’Connell, T. N., Plummer, M. S., Yalamanchi, G., Farley, K. A., Goetz, G. H., Philippe, L., & Shapiro, M. J. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm301850m · Cited by 89

TPI-287, a New Taxane Family Member, Reduces the Brain Metastatic Colonization of Breast Cancer Cells

Fitzgerald, D. P., Emerson, D. L., Qian, Y., Anwar, T., Liewehr, D. J., Steinberg, S. M., Silberman, S., Palmieri, D., & Steeg, P. S. (2012) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-0061 · Cited by 89

Inhibition of Atazanavir Oral Absorption by Lansoprazole Gastric Acid Suppression in Healthy Volunteers

Tomilo, D. L., Smith, P. F., Ogundele, A., DiFrancesco, R., Berenson, C. S., Eberhardt, E., Bednarczyk, E. M., & Morse, G. D. (2006) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.26.3.341 · Cited by 89

Thermodynamic and Structural Effects of Macrocyclization as a Constraining Method in Protein-Ligand Interactions

DeLorbe, J. E., Clements, J. H., Whiddon, B. B., & Martin, S. (2010) · ACS Medicinal Chemistry Letters · doi:10.1021/ml100142y · Cited by 88

Delineating the Contribution of Secretory Transporters in the Efflux of Etoposide Using Madin-Darby Canine Kidney (MDCK) Cells Overexpressing P-Glycoprotein (Pgp), Multidrug Resistance-Associated Protein (MRP1), and Canalicular Multispecific Organic Anion Transporter (cMOAT)

Guo, A., Marinaro, W., Hu, P., & Sinko, P. J. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.4.457 · Cited by 86

Epithelial cells in culture as a model for the intestinal transport of antimicrobial agents

Ranaldi, G., Islam, K., & Sambuy, Y. (1992) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.36.7.1374 · Cited by 85

Selamectin is a potent substrate and inhibitor of human and canine P‐glycoprotein

Griffin, J., Fletcher, N. F., Clemence, R. G., BLANCHFLOWER, S. E., & Brayden, D. J. (2005) · Journal of Veterinary Pharmacology and Therapeutics · doi:10.1111/j.1365-2885.2005.00655.x · Cited by 83

Clinical pharmacodynamics and pharmacokinetics of the antifungal extended‐spectrum triazole posaconazole: an overview

Lipp, H. (2010) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2010.03680.x · Cited by 82

Utilization of an Intramolecular Hydrogen Bond To Increase the CNS Penetration of an NK1 Receptor Antagonist

Ashwood, V. A., Field, M. J., Horwell, D. C., Julien-Larose, C., Lewthwaite, R. A., McCleary, S., Pritchard, M. C., Raphy, J., & Singh, L. (2001) · Journal of Medicinal Chemistry · doi:10.1021/jm010825z · Cited by 82

In vitro and in vivo models for assessing drug efflux transporter activity

Zhang, Y., Bachmeier, C. J., & Miller, D. W. (2003) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00170-9 · Cited by 82

Effects of Orally Active Taxanes on P-Glycoprotein Modulation and Colon and Breast Carcinoma Drug Resistance

Vredenburg, M., Ojima, I., Veith, J. M., Pera, P. J., Kee, K., Cabral, F., Sharma, A. B., Kanter, P. M., Greco, W. R., & Bernacki, R. J. (2001) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/93.16.1234 · Cited by 82

Comparison of activities of rifapentine and rifampin against Mycobacterium tuberculosis residing in human macrophages

Mor, N., Simon, B., Mezo, N., & Heifets, L. B. (1995) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.39.9.2073 · Cited by 81

Design and development of oral drugs for the prophylaxis and treatment of smallpox infection

Painter, G. R., & Hostetler, K. Y. (2004) · Trends in biotechnology · doi:10.1016/j.tibtech.2004.06.008 · Cited by 80

Effect of solubilizing excipients on permeation of poorly water-soluble compounds across Caco-2 cell monolayers

Saha, P., & Kou, J. H. (2000) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/s0939-6411(00)00113-2 · Cited by 79

Making every SAR point count: the development of Chemistry Connect for the large-scale integration of structure and bioactivity data

Mureşan, S., Petrov, P., Southan, C., Kjellberg, M. J., Kogej, T., Tyrchan, C., Varkonyi, P., & Xie, P. H. (2011) · Drug Discovery Today · doi:10.1016/j.drudis.2011.10.005 · Cited by 79

IN VITRO AND IN VIVO CORRELATION OF HEPATIC TRANSPORTER EFFECTS ON ERYTHROMYCIN METABOLISM: CHARACTERIZING THE IMPORTANCE OF TRANSPORTER-ENZYME INTERPLAY

Lam, J. L., Okochi, H., Huang, Y., & Benet, L. Z. (2006) · Drug Metabolism and Disposition · doi:10.1124/dmd.106.009258 · Cited by 79

Digoxin Is Not a Substrate for Organic Anion-Transporting Polypeptide Transporters OATP1A2, OATP1B1, OATP1B3, and OATP2B1 but Is a Substrate for a Sodium-Dependent Transporter Expressed in HEK293 Cells

Taub, M. E., Mease, K. M., Sane, R. S., Watson, C. A., Chen, L.-F., Ellens, H. M., Hirakawa, B. P., Reyner, E. L., Jani, M., & Lee, C. A. (2011) · Drug Metabolism and Disposition · doi:10.1124/dmd.111.040816 · Cited by 77

Differential effects of the immunosuppressive agents cyclosporin A, tacrolimus and sirolimus on drug transport by multidrug resistance proteins

Pawarode, A., Shukla, S., Minderman, H., Fricke, S. M., Pinder, E., O’Loughlin, K. L., Ambudkar, S. V., & Baer, M. R. (2006) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-006-0357-8 · Cited by 76

Formulation strategies for drug delivery of tacrolimus: An overview

Patel, P., Patel, H., Mehta, T. A., & Panchal, S. S. (2012) · International Journal of Pharmaceutical Investigation · doi:10.4103/2230-973x.106981 · Cited by 74

Bioavailability of amiodarone tablets administered with and without food in healthy subjects

Xu, M. J., Mojaverian, P., Doedée, M., Lin, E. T., Weinryb, I., Chiang, S. T., & Kowey, P. R. (2001) · The American Journal of Cardiology · doi:10.1016/s0002-9149(00)01396-5 · Cited by 73

Bridging In Vitro and In Vivo Metabolism and Transport of Faldaprevir in Human Using a Novel Cocultured Human Hepatocyte System, HepatoPac

Ramsden, D., Tweedie, D., Chan, T., Taub, M., & Li, Y. (2014) · Drug Metabolism And Disposition · doi:10.1124/dmd.113.055897 · Cited by 73

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Nomeir, A. A., Kumari, P., Hilbert, M. J., Gupta, S., Loebenberg, D., Cacciapuoti, A. F., Hare, R. S., Miller, G. H., Lin, C., & Cayen, M. N. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.3.727-731.2000 · Cited by 72

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Kis, O., Zastre, J. A., Hoque, M. T., Walmsley, S. L., & Bendayan, R. (2012) · Pharmaceutical Research · doi:10.1007/s11095-012-0942-y · Cited by 70

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Bjornsson, T. D., & Mahony, C. (1983) · Thrombosis Research · doi:10.1016/0049-3848(83)90364-x · Cited by 69

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Hostetler, K. Y. (2010) · Viruses · doi:10.3390/v2102213 · Cited by 68

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Kirken, R. A., & Wang, Y. L. (2003) · Transplantation Proceedings · doi:10.1016/s0041-1345(03)00230-6 · Cited by 67

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Ali, A., Aydın, C., Gildemeister, R. G., Romano, K. P., Cao, H., Özen, A., Soumana, D. I., Newton, A., Petropoulos, C. J., Huang, W., et al. (2013) · ACS Chemical Biology · doi:10.1021/cb400100g · Cited by 66

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Newman, D. J., & Cragg, G. M. L. (2020) · Journal of Natural Products · doi:10.1021/acs.jnatprod.9b01285 · Cited by 7,656

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Newman, D. J., & Cragg, G. M. (2016) · Journal of Natural Products · doi:10.1021/acs.jnatprod.5b01055 · Cited by 5,858

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DeGoey, D. A., Chen, H.-J., Cox, P. B., & Wendt, M. D. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00717 · Cited by 390

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