Discovery of Small Molecules that Bind to K‐Ras and Inhibit Sos‐Mediated Activation
Open accessAbstract
Looking for fragments: A fragment-based screen using NMR spectroscopy was applied to discover ligands that bind to the GTPase K-Ras and modulate the activity of the nucleotide exchange factor Sos. Structural data on how these fragment-derived hits bind to the guanosine diphosphate–K-Ras complex (see picture) provides a starting point for the future discovery of drugs that target K-Ras activation and signaling.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Recently, three studies used similar fragment-based small molecule screening to identify compounds that bind sites on the K-Ras surface and block its SOS-mediated activation.
“Recently, three studies used similar fragment-based small molecule screening to identify compounds that bind sites on the K-Ras surface and block its SOS-mediated activation24–26 suggesting the approach has some promise.”
From Discovery and characterization of small molecules that target the GTPase Ral (2014) · cites this paper as [24]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590 · see citing works
Flagged first, then by citations
Research works printed but not linked: 9
- [1]Hanahan D Weinberg RA Cell 2011 144 646 74 21376230
- [2]Pylayeva-Gupta Y Grabocka E Bar-Sagi D Nat. Rev. Cancer 2011 11 761 74 21993244 PMC3632399
- Laghi L Orbetegli O Bianchi P Zerbi A Di Carlo V Boland CR Malesci A Oncogene 2002 21 4301 6 12082617 b) Lau KS Haigis KM Mol. Cells 2009 28 315 20 19812895 PMC3976423 c) Riely GJ Marks J Pao W Proc. Am. Thorac. Soc 2009 6 201 5 19349489 d) Bos JL Cancer Res 1989 49 4682 9 2547513 e) Yen LC Uen YH Wu DC Lu CY Yu FJ Wu IC Lin SR Wang JY Ann. Surg 2010 251 254 60 20010090
- Chin L Tam A Pomerantz J Wong M Holash J Bardeesy N Shen Q O’Hagan R Pantginis J Zhou H Horner JW Cordon-Cardo C Yancopoulos GD DePinho RA Nature 1999 400 468 72 10440378 b) Podsypanina K Politi K Beverly LJ Varmus HE Proc. Natl. Acad. Sci 2008 105 5242 7 18356293 PMC2278195
- [5]Arkin MR Wells JA Nat. Rev. Drug Discov 2004 3 301 317 15060526
- Shuker SB Hajduk PJ Meadows RP Fesik SW Science 1996 274 1531 4 8929414 b) Hajduk PJ Greer J Nat.Rev.Drug Discov 2007 6 211 9 17290284 c) Jhoti H Cleasby A Verdonk M Williams G Curr Opin Chem Biol 2007 11 485 93 17851109
- Kigawa T Yamaguchi-Nunokawa E Kodama K Matsuda T Yabuki T Matsuda N Ishitani R Nureki O Yokoyama SJ Struct. Funct. Genomics 2002 2 29 35 12836672 b) Ma J Karplus M Proc. Natl. Acad. Sci 1997 94 11905 10 9342335 PMC23651
- [8]Patgiri A Yadav KK Arora PS Bar-Sagi D Nat. Chem. Biol 2011 7 585 7 21765406 PMC3312813
- [9]Boriack-Sjodin PA Margarit SM Bar-Sagi D Kuriyan J Nature 1998 394 337 43 9690470
Cited by
Sorted by citations
K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions
Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A., & Shokat, K. M. (2013) · Nature · doi:10.1038/nature12796 · Cited by 2,557 · see citing works
RAS Proteins and Their Regulators in Human Disease
Simanshu, D. K., Nissley, D. V., & McCormick, F. (2017) · Cell · doi:10.1016/j.cell.2017.06.009 · Cited by 1,943 · see citing works
Drugging the undruggable RAS: Mission Possible?
Cox, A. D., Fesik, S. W., Kimmelman, A. C., Luo, J., & Der, C. J. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4389 · Cited by 1,997 · see citing works
Self-citationTargeting KRAS mutant cancers with a covalent G12C-specific inhibitor
Janes, M. R., Zhang, J., Li, L.-S., Hansen, R., Peters, U., Guo, X., Chen, Y., Babbar, A., Firdaus, S. J., Darjania, L., et al. (2018) · Cell · doi:10.1016/j.cell.2018.01.006 · Cited by 1,172 · see citing works
Targeting RAS–ERK signalling in cancer: promises and challenges
Samatar, A. A., & Poulikakos, P. I. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4281 · Cited by 1,163 · see citing works
RAS-targeted therapies: is the undruggable drugged?
Moore, A. R., Rosenberg, S. C., McCormick, F., & Malek, S. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0068-6 · Cited by 1,103 · see citing works
Small-Molecule Inhibitors of Protein-Protein Interactions: Progressing toward the Reality
Arkin, M. R., Tang, Y., & Wells, J. A. (2014) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.09.001 · Cited by 1,065 · see citing works
RAS isoforms and mutations in cancer at a glance
Hobbs, G. A., Der, C. J., & Rossman, K. L. (2016) · Journal of Cell Science · doi:10.1242/jcs.182873 · Cited by 973 · see citing works
Twenty years on: the impact of fragments on drug discovery
Erlanson, D. A., Fesik, S. W., Hubbard, R. E., Jahnke, W., & Jhoti, H. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.109 · Cited by 1,000 · see citing works
Self-citationStephen, A. G., Esposito, D., Bagni, R. K., & McCormick, F. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.02.017 · Cited by 795 · see citing works
Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations
Hunter, J. C., Manandhar, A., Carrasco, M. A., Gurbani, D., Gondi, S., & Westover, K. D. (2015) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-15-0203 · Cited by 786 · see citing works
Identification of MRTX1133, a Noncovalent, Potent, and Selective KRAS <sup>G12D</sup> Inhibitor
Wang, X., Allen, S., Blake, J. F., Bowcut, V., Briere, D. M., Calinisan, A., Dahlke, J. R., Fell, J. B., Fischer, J. P., Gunn, R. J., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01688 · Cited by 769 · see citing works
Selective inhibition of oncogenic KRAS output with small molecules targeting the inactive state
Patricelli, M. P., Janes, M. R., Li, L.-S., Hansen, R., Peters, U., Kessler, L. V., Chen, Y., Kucharski, J. M., Feng, J., Ely, T., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1105 · Cited by 759 · see citing works
Direct small-molecule inhibitors of KRAS: from structural insights to mechanism-based design
Ostrem, J. M. L., & Shokat, K. M. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.139 · Cited by 641 · see citing works
Small molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling
Zimmermann, G., Papke, B., Ismail, S., Vartak, N., Chandra, A., Hoffmann, M., Hahn, S. A., Triola, G., Wittinghofer, A., Bastiaens, P. I. H., et al. (2013) · Nature · doi:10.1038/nature12205 · Cited by 596 · see citing works
Modulators of Protein–Protein Interactions
Milroy, L.-G., Grossmann, T. N., Hennig, S., Brunsveld, L., & Ottmann, C. (2014) · Chemical Reviews · doi:10.1021/cr400698c · Cited by 497 · see citing works
Drugging an undruggable pocket on KRAS
Kessler, D., Gmachl, M., Mantoulidis, A., Martin, L. J., Zoephel, A., Mayer, M., Gollner, A., Covini, D., Fischer, S., Gerstberger, T., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1904529116 · Cited by 449 · see citing works
Self-citationTargeting protein–protein interactions as an anticancer strategy
Ivanov, A. A., Khuri, F. R., & Fu, H. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.04.007 · Cited by 401 · see citing works
Papke, B., & Der, C. J. (2017) · Science · doi:10.1126/science.aam7622 · Cited by 399 · see citing works
Hillig, R. C., Sautier, B., Schroeder, J., Moosmayer, D., Hilpmann, A., Stegmann, C. M., Werbeck, N. D., Briem, H., Boemer, U., Weiske, J., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1812963116 · Cited by 388 · see citing works
Cook, D. R., Rossman, K. L., & Der, C. J. (2014) · Oncogene · doi:10.1038/onc.2013.362 · Cited by 378 · see citing works
Ras Conformational Ensembles, Allostery, and Signaling
Lu, S., Jang, H., Muratcioglu, S., Gursoy, A., Keskin, O., Nussinov, R., & Zhang, J. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00542 · Cited by 355 · see citing works
McCormick, F. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2662 · Cited by 320 · see citing works
Inhibition of RAS function through targeting an allosteric regulatory site
Spencer-Smith, R., Koide, A., Zhou, Y., Eguchi, R. R., Sha, F., Gajwani, P., Santana, D., Gupta, A., Jacobs, M., Herrero-Garcia, E., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2231 · Cited by 283 · see citing works
Small‐Molecule Inhibitors of the Interaction between the E3 Ligase VHL and HIF1α
Buckley, D. L., Gustafson, J. L., Van Molle, I., Roth, A. G., Tae, H. S., Gareiss, P. C., Jorgensen, W. L., Ciulli, A., & Crews, C. M. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201206231 · Cited by 302 · see citing works
Hunter, J. C., Gurbani, D., Ficarro, S. B., Carrasco, M. A., Lim, S. M., Choi, H. G., Xie, T., Marto, J. A., Chen, Z., Gray, N. S., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1404639111 · Cited by 242 · see citing works
Trivalent PROTACs enhance protein degradation via combined avidity and cooperativity
Imaide, S., Riching, K. M., Makukhin, N., Vetma, V., Whitworth, C., Hughes, S. J., Trainor, N., Mahan, S. D., Murphy, N., Cowan, A. D., et al. (2021) · Nature Chemical Biology · doi:10.1038/s41589-021-00878-4 · Cited by 251 · see citing works
The Structural Basis of Oncogenic Mutations G12, G13 and Q61 in Small GTPase K-Ras4B
Lu, S., Jang, H., Nussinov, R., & Zhang, J. (2016) · Scientific Reports · doi:10.1038/srep21949 · Cited by 219 · see citing works
Targeting Protein-Protein Interaction by Small Molecules
Jin, L., Wang, W., & Fang, G. (2014) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011613-140028 · Cited by 195 · see citing works
Systematic Targeting of Protein–Protein Interactions
Modell, A. E., Blosser, S. L., & Arora, P. S. (2016) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2016.05.008 · Cited by 184 · see citing works
Drugging Ras GTPase: a comprehensive mechanistic and signaling structural view
Lu, S., Jang, H., Gu, S., Zhang, J., & Nussinov, R. (2016) · Chemical Society Reviews · doi:10.1039/c5cs00911a · Cited by 188 · see citing works
Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange
Burns, M. C., Sun, Q., Daniels, R. N., Camper, D., Kennedy, J. P., Phan, J., Olejniczak, E. T., Lee, T., Waterson, A. G., Rossanese, O. W., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1315798111 · Cited by 199 · see citing works
Self-citationSurvival of pancreatic cancer cells lacking KRAS function
Muzumdar, M. D., Chen, P.-Y., Dorans, K. J., Chung, K. M., Bhutkar, A., Hong, E., Noll, E. M., Sprick, M. R., Trumpp, A., & Jacks, T. (2017) · Nature Communications · doi:10.1038/s41467-017-00942-5 · Cited by 177 · see citing works
KRAS G12C Game of Thrones, which direct KRAS inhibitor will claim the iron throne?
Nagasaka, M., Li, Y., Sukari, A., Ou, S.-H. I., Al-Hallak, M. N., & Azmi, A. S. (2020) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2020.101974 · Cited by 185 · see citing works
Pharmacological targeting of RAS: recent success with direct inhibitors
O’Bryan, J. P. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2018.10.021 · Cited by 153 · see citing works
Chemical acylation of an acquired serine suppresses oncogenic signaling of K-Ras(G12S)
Zhang, Z., Guiley, K. Z., & Shokat, K. M. (2022) · Nature Chemical Biology · doi:10.1038/s41589-022-01065-9 · Cited by 153 · see citing works
Discovery and characterization of small molecules that target the GTPase Ral
Yan, C., Liu, D., Li, L., Wempe, M. F., Guin, S., Khanna, M., Meier, J., Hoffman, B., Owens, C., Wysoczynski, C. L., et al. (2014) · Nature · doi:10.1038/nature13713 · Cited by 150 · see citing works
Potent and Selective Covalent Quinazoline Inhibitors of KRAS G12C
Zeng, M., Lu, J., Li, L., Feru, F., Quan, C., Gero, T. W., Ficarro, S. B., Xiong, Y., Ambrogio, C., Paranal, R. M., et al. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.06.017 · Cited by 136 · see citing works
Current therapy of KRAS-mutant lung cancer
Ghimessy, A., Radeczky, P., Laszlo, V., Hegedus, B., Renyi-Vamos, F., Fillinger, J., Klepetko, W., Lang, C., Dome, B., & Megyesfalvi, Z. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09903-9 · Cited by 115 · see citing works
GTP-State-Selective Cyclic Peptide Ligands of K-Ras(G12D) Block Its Interaction with Raf
Zhang, Z., Gao, R., Hu, Q., Peacock, H., Peacock, D. M., Dai, S., Shokat, K. M., & Suga, H. (2020) · ACS Central Science · doi:10.1021/acscentsci.0c00514 · Cited by 124 · see citing works
A RAS Renaissance: Emerging Targeted Therapies for KRAS-Mutated Non–Small Cell Lung Cancer
Vasan, N., Boyer, J. L., & Herbst, R. S. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1762 · Cited by 102 · see citing works
Expanding the scope of electrophiles capable of targeting K-Ras oncogenes
McGregor, L. M., Jenkins, M. L., Kerwin, C., Burke, J. E., & Shokat, K. M. (2017) · Biochemistry · doi:10.1021/acs.biochem.7b00271 · Cited by 97 · see citing works
Self-citationIssahaku, A. R., Mukelabai, N., Agoni, C., Rudrapal, M., Aldosari, S. M., Almalki, S. G., & Khan, J. (2022) · Scientific Reports · doi:10.1038/s41598-022-22668-1 · Cited by 93 · see citing works
Fang, Z., Marshall, C. B., Nishikawa, T., Gossert, A. D., Jansen, J. M., Jahnke, W., & Ikura, M. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2018.07.009 · Cited by 86 · see citing works
Discovery of High-Affinity Noncovalent Allosteric KRAS Inhibitors That Disrupt Effector Binding
McCarthy, M. J., Pagba, C. V., Prakash, P., Naji, A. K., van der Hoeven, D., Liang, H., Gupta, A. K., Zhou, Y., Cho, K.-J., Hancock, J. F., et al. (2019) · ACS Omega · doi:10.1021/acsomega.8b03308 · Cited by 90 · see citing works
Bröker, J., Waterson, A. G., Smethurst, C., Kessler, D., Böttcher, J., Mayer, M., Gmaschitz, G., Phan, J., Little, A., Abbott, J. R., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01120 · Cited by 96 · see citing works
Self-citationStrategies to tackle RAS-mutated metastatic colorectal cancer
Patelli, G., Tosi, F., Amatu, A., Mauri, G., Curaba, A., Patanè, D. A., Pani, A., Scaglione, F., Siena, S., & Sartore-Bianchi, A. (2021) · ESMO Open · doi:10.1016/j.esmoop.2021.100156 · Cited by 86 · see citing works
Sogabe, S., Kamada, Y., Miwa, M., Niida, A., Sameshima, T., Kamaura, M., Yonemori, K., Sasaki, S., Sakamoto, J.-I., & Sakamoto, K. (2017) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.7b00128 · Cited by 83 · see citing works
High-affinity interaction of the K-Ras4B hypervariable region with the RAS active site
Chavan, T. S., Jang, H., Khavrutskii, L., Abraham, S. J., Banerjee, A., Freed, B. C., Johannessen, L., Tarasov, S. G., Gaponenko, V., Nussinov, R., et al. (2015) · Biophysical Journal · doi:10.1016/j.bpj.2015.09.034 · Cited by 79 · see citing works
Drugging K-RasG12C through covalent inhibitors: Mission possible?
Ni, D., Li, X., He, X., Zhang, H., Zhang, J., & Lu, S. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.06.007 · Cited by 73 · see citing works
Inhibitors of Ras–SOS Interactions
Lu, S., Jang, H., Zhang, J., & Nussinov, R. (2016) · ChemMedChem · doi:10.1002/cmdc.201500481 · Cited by 72 · see citing works
Protein–Protein Interactions: Emerging Oncotargets in the RAS-ERK Pathway
García-Gómez, R., Bustelo, X. R., & Crespo, P. (2018) · Trends in Cancer · doi:10.1016/j.trecan.2018.07.002 · Cited by 72 · see citing works
Plucking the high hanging fruit: A systematic approach for targeting protein–protein interactions
Raj, M., Bullock, B. N., & Arora, P. S. (2013) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2012.11.023 · Cited by 66 · see citing works
Bifunctional Small‐Molecule Ligands of K‐Ras Induce Its Association with Immunophilin Proteins
Zhang, Z., & Shokat, K. M. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201910124 · Cited by 66 · see citing works
An engineered protein antagonist of K-Ras/B-Raf interaction
Kauke, M. J., Traxlmayr, M. W., Parker, J. A., Kiefer, J. D., Knihtila, R., McGee, J., Verdine, G., Mattos, C., & Wittrup, K. D. (2017) · Scientific Reports · doi:10.1038/s41598-017-05889-7 · Cited by 64 · see citing works
miR-1298 Inhibits Mutant KRAS-Driven Tumor Growth by Repressing FAK and LAMB3
Zhou, Y., Dang, J., Chang, K.-Y., Yau, E., Aza-Blanc, P., Moscat, J., & Rana, T. M. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2936 · Cited by 54 · see citing works
Cierpicki, T., & Grembecka, J. (2015) · Immunological Reviews · doi:10.1111/imr.12244 · Cited by 53 · see citing works
Sayyed-Ahmad, A., Prakash, P., & Gorfe, A. A. (2017) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.25317 · Cited by 54 · see citing works
Differential dynamics of RAS isoforms in GDP- and GTP-bound states
Kapoor, A., & Travesset, A. (2015) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.24805 · Cited by 53 · see citing works
Discovery of Novel KRAS-PDEδ Inhibitors by Fragment-Based Drug Design
Chen, L., Zhuang, C., Lu, J., Jiang, Y., & Sheng, C. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00057 · Cited by 33 · see citing works
Structural Biology-Inspired Discovery of Novel KRAS–PDEδ Inhibitors
Jiang, Y., Zhuang, C., Chen, L., Lu, J., Dong, G., Miao, Z., Zhang, W., Li, J., & Sheng, C. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01243 · Cited by 34 · see citing works
Mutant and wild-type Ras: co-conspirators in cancer
Hayes, T. K., & Der, C. J. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0521 · Cited by 13 · see citing works
Therapeutic Targeting the Allosteric Cysteinome of RAS and Kinase Families
Li, L., Meyer, C., Zhou, Z.-W., Elmezayen, A., & Westover, K. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167626 · Cited by 14 · see citing works
- Authors
- Sun, Q., Burke, J. P., Phan, J., Burns, M. C., Olejniczak, E. T., Waterson, A. G., Lee, T., Rossanese, O. W., & Fesik, S. W.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Fesik, Stephen W.
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2012-05-08
- Volume
- 51
- Issue
- 25
- Pages
- 6140-6143
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- PMC
- PMC3620661
- OpenAlex
- W1971102429
- Cited by
- 490
- References
- 1
- Citations by year
- 2026: 12 · 2025: 26 · 2024: 26 · 2023: 31 · 2022: 35 · 2021: 31 · 2020: 42 · 2019: 36 · 2018: 35 · 2017: 39 · 2016: 42 · 2015: 40 · 2014: 45 · 2013: 37 · 2012: 10
- FWCI
- 16.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Angewandte Chemie International Edition (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Cancer Research UK (11566)
- National Institutes of Health (DP1OD006933, 5RC2A148375)
- U.S. Public Health Service (5P50A095103-09)
- National Cancer Institute (DP1CA174419, P50CA095103, RC2CA148375)
- National Institute of General Medical Sciences (T32GM007347)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- KRAS, SO, nucleotide exchange factor, fragment screening, NMR fragment screening, small-molecule ligands, GTPase activation, guanosine diphosphate, Ras signaling, drug discovery
- MeSH terms
- Genes, ras, Molecular Structure, Crystallography, X-Ray, Son of Sevenless Proteins, Small Molecule Libraries
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
