Cited by 328Computational Drug Discovery MethodsStatistical Methods in Clinical TrialsOptimal Experimental Design Methods

The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.

A New Bliss Independence Model to Analyze Drug Combination Data

Open access

Zhao, Wei, Sachsenmeier, Kris, Zhang, Lanju, Sult, Erin, Hollingsworth, Robert E., Yang, Harry·2014·SLAS Discovery

DOI 10.1177/1087057114521867

Open this paper in CoChat — free account Open PDF

Abstract

The Bliss independence model is widely used to analyze drug combination data when screening for candidate drug combinations. The method compares the observed combination response (Y(O)) with the predicted combination response (Y(P)), which was obtained based on the assumption that there is no effect from drug-drug interactions. Typically, the combination effect is declared synergistic if Y(O) is greater than Y(P). However, this method lacks statistical rigor because it does not take into account the variability of the response measures and can frequently cause false-positive claims. In this article, we introduce a two-stage response surface model to describe the drug interaction across all dose combinations tested. This new method enables robust statistical testing for synergism at any dose combination, thus reducing the risk of false positives. The use of the method is illustrated through an application describing statistically significant "synergy regions" for candidate drug combinations targeting epidermal growth factor receptor and the insulin-like growth factor 1 receptor.

Integrity signals

Registry

Crossref · 10.1177/1087057114521867

Cites

14 of 14 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

The search for synergy: a critical review from a response surface perspective.
Greco, W. R., Bravo, G., & Parsons, J. C. (1995) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06847-4 · Cited by 1,445
Probability Theory and Mathematical Statistics
(1996) · doi:10.1142/2898 · Cited by 1,406
Activation of Multiple Proto-oncogenic Tyrosine Kinases in Breast Cancer via Loss of the PTPN12 Phosphatase
Sun, T., Aceto, N., Meerbrey, K. L., Kessler, J. D., Zhou, C., Migliaccio, I., Nguyen, D. X., Pavlova, N. N., Botero, M. F., Huang, J., et al. (2011) · Cell · doi:10.1016/j.cell.2011.02.003 · Cited by 281 · cited 4×
“I Y Y M a b ab O ab P = − = + , , ( | , ) Γ ε, (3)”
BackgroundMethodInfluential
A global analysis of cross-talk in a mammalian cellular signalling network
Natarajan, M., Lin, K.-M., Hsueh, R. C., Sternweis, P. C., & Ranganathan, R. (2006) · Nature Cell Biology · doi:10.1038/ncb1418 · Cited by 235 · cited 1×
“Average percentage inhibition is usually used when replicates are available and a conclusion can be drawn by strictly following equations (1) and (2).”
Method
Probability Theory and Mathematical Statistics.
Bartholomew, D. J., & Fisz, M. (1964) · Biometrika · doi:10.2307/2334227 · Cited by 161
A stable IgG-like bispecific antibody targeting the epidermal growth factor receptor and the type I insulin-like growth factor receptor demonstrates superior anti-tumor activity
Dong, J., Sereno, A., Aivazian, D., Langley, E. J., Miller, B., Snyder, W. B., Chan, E., Cantele, M., Morena, R., Joseph, I. B. J., et al. (2011) · mAbs · doi:10.4161/mabs.3.3.15188 · Cited by 80
Activation of the Insulin-like Growth Factor-1 Receptor Induces Resistance to Epidermal Growth Factor Receptor Antagonism in Head and Neck Squamous Carcinoma Cells
Jameson, M. J., Beckler, A. D., Taniguchi, L. E., Allak, A., VanWagner, L. B., Lee, N. G., Thomsen, W. C., Hubbard, M. A., & Thomas, C. Y. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0294 · Cited by 79
The EGF receptor interacts with the type 1 IGF receptor and regulates its stability
Riedemann, J., Takiguchi, M., Sohail, M., & Macaulay, V. M. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.02.012 · Cited by 77
Dual inhibition of epidermal growth factor receptor and insulin‐like growth factor receptor I: Reduction of angiogenesis and tumor growth in cutaneous squamous cell carcinoma
Galer, C. E., Corey, C. L., Wang, Z., Younes, M. N., Gomez‐Rivera, F., Jasser, S. A., Ludwig, D. L., El‐Naggar, A. K., Weber, R. S., & Myers, J. N. (2010) · Head & Neck · doi:10.1002/hed.21419 · Cited by 53
Rational Design of Cancer-Drug Combinations
Ramaswamy, S. (2007) · New England Journal of Medicine · doi:10.1056/nejmcibr072593 · Cited by 48 · cited 1×
“Average percentage inhibition is usually used when replicates are available and a conclusion can be drawn by strictly following equations (1) and (2).”
Method

Show all 14 references

Sorted by citations

Items 101–200 of 328

Caveolin-mediated cytosolic delivery of spike nanoparticle enhances antitumor immunity of neoantigen vaccine for hepatocellular carcinoma
Lin, Z., Jiang, C., Wang, P., Chen, Q., Wang, B., Fu, X., Liang, Y., Zhang, D., Zeng, Y., & Liu, X. (2023) · Theranostics · doi:10.7150/thno.85843 · Cited by 19
“Assuming that two drugs, A and B, both have the ability to inhibit tumor growth, with drug A inhibiting Ya percent of tumor growth at a dose a, and drug B inhibiting Yb percent of tumor growth at a dose b, the combination of inhibition percent Yab,P can be estimated by the complete additivity principle of probability…”
Altering microtubule dynamics is synergistically toxic with spindle assembly checkpoint inhibition
Schukken, K. M., Lin, Y., Bakker, P. L., Schubert, M., Preuß, S. F., Simon, J. E., van den Bos, H., Štorchová, Z., Colomé‐Tatché, M., Bastians, H., et al. (2020) · Life Science Alliance · doi:10.26508/lsa.201900499 · Cited by 18
“The combined effects of aneuploidy and ZLN005 act synergistically as assessed by a Bliss independence test (50% stronger effect than additive, P = 3.2E-3, [Zhao et al, 2014]).”
Background
JMJD6 Rewires ATF4-Dependent Glutathione Metabolism to Confer Ferroptosis Resistance in SPOP-Mutated Prostate Cancer
Zhang, C., Ding, J., Lim, K. S., Zhou, W., Miao, W., Wu, S., Liu, H., Huang, D., Chen, C., He, H., et al. (2025) · Cancer Research · doi:10.1158/0008-5472.can-23-2796 · Cited by 18
Addressing antimicrobial resistance with the IDentif.AI platform: Rapidly optimizing clinically actionable combination therapy regimens against nontuberculous mycobacteria
Mukherjee, D., Wang, P., Hooi, L., Sandhu, V., You, K., Blasiak, A., Chow, E. K., Ho, D., & Ee, P. L. R. (2022) · Theranostics · doi:10.7150/thno.73078 · Cited by 18
“The data set was subsequently uploaded to SynergyFinder to perform Bliss independence model analysis [53, 54, 71].”
Method
An Anti-PSMA Immunotoxin Reduces Mcl-1 and Bcl2A1 and Specifically Induces in Combination with the BAD-Like BH3 Mimetic ABT-737 Apoptosis in Prostate Cancer Cells
Masilamani, A. P., Dettmer‐Monaco, V., Monaco, G., Cathomen, T., Kuckuck, I., Schultze-Seemann, S., Huber, N., & Wolf, P. (2020) · Cancers · doi:10.3390/cancers12061648 · Cited by 18
“was used to determine synergistic cytotoxicity of the immunotoxin in combination with ABT-737 on the target cells [37].”
BackgroundMethod
Efficacy of a Combination of N-Palmitoylethanolamide, Beta-Caryophyllene, Carnosic Acid, and Myrrh Extract on Chronic Neuropathic Pain: A Preclinical Study
Fotio, Y., Alaoui, A. A. E., Borruto, A. M., Acciarini, S., Giordano, A., & Ciccocioppo, R. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00711 · Cited by 18
Identification of Promising Antifungal Drugs against Scedosporium and Lomentospora Species after Screening of Pathogen Box Library
Rollin‐Pinheiro, R., Borba-Santos, L. P., Xisto, M. I. D. D. S., de Castro-Almeida, Y., Rochetti, V. P., Rozental, S., & Barreto‐Bergter, E. (2021) · Journal of Fungi · doi:10.3390/jof7100803 · Cited by 16
“Bliss independence model was performed according to Meletiadis and colleagues and Zhao and colleagues [50,51].”
Method
Combination p53 activation and BCL-xL/BCL-2 inhibition as a therapeutic strategy in high-risk and relapsed acute lymphoblastic leukemia
Bell, H. L., Blair, H. J., Gosling, S. J. J., Galler, M., Astley, D. J., Moorman, A. V., Heidenreich, O. T., Veal, G. J., van Delft, F. W., Lunec, J., et al. (2024) · Leukemia · doi:10.1038/s41375-024-02241-7 · Cited by 16
“Drug combination effects and synergy scores were analyzed using the Bliss independence model [20, 21].”
Significant Therapeutic Efficacy with Combined Radioimmunotherapy and Cetuximab in Preclinical Models of Colorectal Cancer
Vassileva, V., Rajkumar, V. S., Mazzantini, M., Robson, M. P., Badar, A., Sharma, S. K., Årstad, E., Hochhauser, D., Lythgoe, M. F., Boxer, G. M., et al. (2015) · Journal of Nuclear Medicine · doi:10.2967/jnumed.115.157362 · Cited by 16
Combined targeting of MEK and the glucocorticoid receptor for the treatment of RAS-mutant multiple myeloma
Sriskandarajah, P., Brandon, A. D. H., Macleod, K., Carragher, N. O., Kirkin, V., Kaiser, M., & Whittaker, S. R. (2020) · BMC Cancer · doi:10.1186/s12885-020-06735-2 · Cited by 14
“Synergy was assessed using the Bliss Independence model, where values greater than 0 indicated synergy [30] (Fig.”
Method
Synergistic cytotoxicity of dual PI3K/mTOR and FLT3 inhibition in FLT3-ITD AML cells
Darici, S., Zavatti, M., Braglia, L., Accordi, B., Serafin, V., Horne, G. A., Manzoli, L., Palumbo, C., Huang, X., Jørgensen, H. G., et al. (2021) · Advances in Biological Regulation · doi:10.1016/j.jbior.2021.100830 · Cited by 16
Enrichment of Antibiotic Resistance Genes on Plastic Waste in Aquatic Ecosystems, Aquatic Animals, and Fishery Products
Rossi, F., Santonicola, S., & Colavita, G. (2025) · Antibiotics · doi:10.3390/antibiotics14111106 · Cited by 17
Anti-Cancer Effects of an Optimised Combination of Ginsenoside Rg3 Epimers on Triple Negative Breast Cancer Models
Nakhjavani, M., Smith, E., Palethorpe, H. M., Tomita, Y., Yeo, K. K. L., Price, T. J., Townsend, A. R., & Hardingham, J. E. (2021) · Pharmaceuticals · doi:10.3390/ph14070633 · Cited by 16
Effective combination treatments for breast cancer inhibition by FOXM1 inhibitors with other targeted cancer drugs
Guillen, V. S., Ziegler, Y., Gopinath, C., Kumar, S., Dey, P., Plotner, B. N., Dawson, N. Z., Kim, S. H., Katzenellenbogen, J. A., & Katzenellenbogen, B. S. (2023) · Breast Cancer Research and Treatment · doi:10.1007/s10549-023-06878-3 · Cited by 15
Development of a flow cytometric method for quantification of BCL‐2 family members in chronic lymphocytic leukemia and correlation with sensitivity to BCL‐2 family inhibitors
Smith, M. L., Chyla, B., McKeegan, E. M., & Tahir, S. K. (2016) · Cytometry Part B Clinical Cytometry · doi:10.1002/cyto.b.21383 · Cited by 15
“The Bliss independence model was used to assess combination responses (25).”
Method
Predicting Drug Synergism by Means of Non-Negative Matrix Tri-Factorization
Pinoli, P., Ceddia, G., Ceri, S., & Masseroli, M. (2021) · IEEE Transactions on Computational Biology and Bioinformatics · doi:10.1109/tcbb.2021.3091814 · Cited by 15
The fungal expel of 5-fluorocytosine derived fluoropyrimidines mitigates its antifungal activity and generates a cytotoxic environment
Sastré-Velásquez, L. E., Dallemulle, A., Kühbacher, A., Baldin, C., Alcázar‐Fuoli, L., Niedrig, A., Müller, C., & Gsaller, F. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1011066 · Cited by 15
“Independence Model [36] was used to analyze the potential synergistic interactions among the 455”
Method
Enhanced Sestrin expression through Tanshinone 2A treatment improves PI3K-dependent inhibition of glioma growth
Schaf, J., Shinhmar, S., Zeng, Q., Pardo, O. E., Beesley, P. W., Syed, N., & Williams, R. S. B. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01462-6 · Cited by 16
“4H) which provided synergistic inhibition of mTORC1 signalling [28].”
BackgroundMethod
Venetoclax resistance in acute lymphoblastic leukemia is characterized by increased mitochondrial activity and can be overcome by co-targeting oxidative phosphorylation
Enzenmüller, S., Niedermayer, A., Seyfried, F., Muench, V., Tews, D., Rupp, U., Tausch, E., Groß, A., Fischer‐Posovszky, P., Walther, P., et al. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06864-7 · Cited by 16
“Combination effects and synergy scores were analyzed (Synergy ﬁ nder, https://synergy ﬁ nder. ﬁ mm. ﬁ /synergy/20240318114830462623/) using the Bliss independence model [22 – 24].”
Dual targeting of EGFR and ERBB2 pathways produces a synergistic effect on cancer cell proliferation and migration in vitro
Gray, M., Lee, S., McDowell, A. L., Erskine, M., Loh, Q. T. M., Grice, O., Argyle, D. J., & Bergkvist, G. T. (2016) · Veterinary and Comparative Oncology · doi:10.1111/vco.12230 · Cited by 14
“Potential synergistic effects of dual targeting of the receptors was investigated in accordance to the Bliss Additivism model.(33) Here we report that EGFR and ERBB2 combined targeting by siRNAs produced a synergistic effect.”
MethodResult
Vitamin D Receptor Activation Attenuates Hippo Pathway Effectors and Cell Survival in Metastatic Neuroblastoma
Ladumor, Y., Seong, B. K. A., Hallett, R. M., Valencia-Sama, I., Adderley, T., Wang, Y., Kee, L., Gont, A., Kaplan, D. R., & Irwin, M. S. (2022) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-21-0425 · Cited by 14
The potential of PARP as a therapeutic target across pediatric solid malignancies
Keller, K. M., Koetsier, J., Schild, L. G., Amo-Addae, V., Eising, S., van den Handel, K., Ober, K., Koopmans, B., Essing, A. H. W., van den Boogaard, M. L., et al. (2023) · BMC Cancer · doi:10.1186/s12885-022-10319-7 · Cited by 13
“To this end, we performed a similar method and calculated three outcome metrics for each combination: 1) fold change in maximum effect at the highest library drug concentration (∆Emax), 2) fold change in IC50 value (∆IC50) and 3) average synergy score according to the bliss independence model [22].”
Method
Pharmacokinetics–Pharmacodynamics Modeling for Evaluating Drug–Drug Interactions in Polypharmacy: Development and Challenges
Zhao, D., Huang, P. C., Yu, L., & He, Y. T. (2024) · Clinical Pharmacokinetics · doi:10.1007/s40262-024-01391-2 · Cited by 14
“Bliss and his associates introduced the Bliss independence model to evaluate the efficacy of drugs using the independence criterion, which notably disregards the nonlinearity of dose–response relationships [139].”
New Insights in Routine Procedure for Mathematical Evaluation of in vitro Cytotoxicity Data from Cancer Cell Lines
Zaharieva, M. M., Trochopoulos, A., Dimitrova, L. L., Berger, M. R., Najdenski, H. M., Konstantinov, S., & Kroumov, A. D. (2018) · International Journal Bioautomation · doi:10.7546/ijba.2018.22.2.87-106 · Cited by 13
Combination treatment with tenapanor and sevelamer synergistically reduces urinary phosphorus excretion in rats
King, A. J., Kohler, J. N., Fung, C., Jiang, Z., Quach, A., Kumaraswamy, P., Chertow, G. M., & Rosenbaum, D. P. (2020) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00137.2020 · Cited by 13
“on the observed effect of each individual agent administered alone, with the observed effect of combination treatment (37).”
BackgroundMethod
Promising Antifungal Molecules against Mucormycosis Agents Identified from Pandemic Response Box®: In Vitro and In Silico Analyses
Xisto, M. I. D. D. S., Rollin‐Pinheiro, R., de Castro-Almeida, Y., dos Santos, G. M. P., Rochetti, V. P., Borba-Santos, L. P., Fontes, Y. D. S., Ferreira‐Pereira, A., Rozental, S., & Barreto‐Bergter, E. (2023) · Journal of Fungi · doi:10.3390/jof9020187 · Cited by 12
“The Bliss independence model calculation was performed according to Meletiadis and colleagues and Zhao and colleagues [22,23].”
Method
Silmitasertib-induced macropinocytosis promoting DDP intracellular uptake to enhance cell apoptosis in oral squamous cell carcinoma
Song, S., Xia, X., Qi, J., Hu, X., Chen, Q., Liu, J., Ji, N., & Zhao, H. (2021) · Drug Delivery · doi:10.1080/10717544.2021.2000677 · Cited by 12
“The new bliss independence model calculation formula (Zhao et al., 2014) was used to calculate the combined inhibition rate of the two drugs.”
Method
Norethindrone suppress the germ cell development via androgen receptor resulting in male bias
Long, X.-B., Shi, W., Yao, C.-R., Li, S., Zhang, J., Lu, Z., Ma, D.-D., Jiang, Y., & Ying, G. (2023) · Aquatic Toxicology · doi:10.1016/j.aquatox.2023.106604 · Cited by 12
Antitumor Synergism and Enhanced Survival with a Tumor Vasculature–Targeted Enzyme Prodrug System, Rapamycin, and Cyclophosphamide
Krais, J. J., Virani, N. A., McKernan, P., Nguyen, Q. D., Fung, K., Sikavitsas, V. I., Kurkjian, C. D., & Harrison, R. G. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-16-0263 · Cited by 12
“Assessment for synergism of combination therapies was performed using the Bliss independence model on primary tumor growth inhibition (47, 48).”
Method
Light-activated quantum dot potentiation of antibiotics to treat drug-resistant bacterial biofilms
Stamo, D. F., Nagpal, P., & Chatterjee, A. (2021) · Nanoscale Advances · doi:10.1039/d1na00056j · Cited by 12
Synergistic Activity of Repurposed Peptide Drug Glatiramer Acetate with Tobramycin against Cystic Fibrosis Pseudomonas aeruginosa
Murphy, R. A., Coates, M. S., Thrane, S., Sabnis, A., Harrison, J., Schelenz, S., Edwards, A. M., Vorup‐Jensen, T., & Davies, J. C. (2022) · Microbiology Spectrum · doi:10.1128/spectrum.00813-22 · Cited by 11
“Synergy between the activities of glatiramer acetate and tobramycin was tested for each 182 strain from colony counts, as previously described (37).”
Method
MEK inhibition causes BIM stabilization and increased sensitivity to BCL-2 family member inhibitors in RAS-MAPK-mutated neuroblastoma
Eleveld, T. F., Vernooij, L., Schild, L. G., Koopmans, B., Alles, L. K., Ebus, M. E., Dandis, R., van Tinteren, H., Caron, H. N., Köster, J., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2023.1130034 · Cited by 11
“Bliss independence scores were calculated to measure synergy between trametinib and each of the tested concentrations of BCL-2 family inhibitors (17).”
Method
Metformin Suppresses Stemness of Non-Small-Cell Lung Cancer Induced by Paclitaxel through FOXO3a
Tang, Z., Zhang, Y., Yu, Z., & Luo, Z. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242316611 · Cited by 14
“If the combination effect is higher than the predicted value, the interaction is synergistic; if it is lower than the predicted value, the interaction is antagonistic; otherwise, the effect is additive and there is no interaction [63].”
Background
Miltefosine: A Repurposing Drug against Mucorales Pathogens
Xisto, M. I. D. D. S., Rollin‐Pinheiro, R., Rochetti, V. P., de Castro-Almeida, Y., Borba-Santos, L. P., dos Santos, G. M. P., Cypriano, J. B. S., Abreu, F. D. Á., Rozental, S., & Barreto‐Bergter, E. (2023) · Journal of Fungi · doi:10.3390/jof9121166 · Cited by 11
“The Bliss independence model was performed according to Meletiadis and colleagues and Zhao and colleagues [29,30].”
Method
The polyamine transporter ATP13A3 mediates difluoromethylornithine‐induced polyamine uptake in neuroblastoma
Azfar, M., Gao, W., den Haute, C. V., Xiao, L., Karsa, M., Pandher, R., Karsa, A., Spurling, D., Ronca, E., Bongers, A., et al. (2025) · Molecular Oncology · doi:10.1002/1878-0261.13789 · Cited by 11
“8B) [22].”
HTSplotter: An end-to-end data processing, analysis and visualisation tool for chemical and genetic in vitro perturbation screening
Nunes, C., Anckaert, J., Vloed, F. D., Wyn, J. D., Durinck, K., Vandesompele, J., Speleman, F., & Vermeirssen, V. (2024) · PLoS ONE · doi:10.1371/journal.pone.0296322 · Cited by 10
“Dose-effect based models work if monotherapy dose-response curves are well characterized, which, depending on the response of a cell line to a drug dose range treatment, might not be achievable [19, 20].”
BackgroundMethod
Chromosome 11q loss and MYCN amplification demonstrate synthetic lethality with checkpoint kinase 1 inhibition in neuroblastoma
Keller, K. M., Eleveld, T. F., Schild, L. G., van den Handel, K., van den Boogaard, M. L., Amo-Addae, V., Eising, S., Ober, K., Koopmans, B., Looijenga, L. H. J., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.929123 · Cited by 11
“Following combination treatment, cell viability was calculated and synergy was evaluated using the bliss independence model (29).”
Method
Biochemical reaction network topology defines dose-dependent Drug–Drug interactions
Babaei, M., Evers, T. M. J., Shokri, F., Altucci, L., de Lange, E. C. M., & Mashaghi, A. (2023) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2023.106584 · Cited by 11
Identification of isoform-selective hydroxamic acid derivatives that potently reactivate HIV from latency
Heffern, E., Ramani, R., Marshall, G. R., & Kyei, G. B. (2019) · Journal of Virus Eradication · doi:10.1016/s2055-6640(20)30057-1 · Cited by 11
“Bliss independence model and isobole analysis We used the Bliss independence model, which is one of the ways to differentiate between additive and synergistic effects of two combined compounds, which has been previously described [10,23].”
Method
Vincristine Enhances the Efficacy of MEK Inhibitors in Preclinical Models of KRAS-mutant Colorectal Cancer
Ghosh, S., Fan, F., Powell, R. T., Roszik, J., Park, Y. S., STEPHAN, C. C., Sebastian, M. M., Tan, L., Sorokin, A. V., Lorenzi, P. L., et al. (2023) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-23-0110 · Cited by 10
SHP2 Inhibition with TNO155 Increases Efficacy and Overcomes Resistance of ALK Inhibitors in Neuroblastoma
Valencia-Sama, I., Kee, L., Christopher, G., Ohh, M., Layeghifard, M., Shlien, A., Hayes, M. N., & Irwin, M. S. (2023) · Cancer Research Communications · doi:10.1158/2767-9764.crc-23-0234 · Cited by 10
In silico assessment on TdP risks of drug combinations under CiPA paradigm
Qauli, A. I., Marcellinus, A., Setiawan, M. A., Zain, A. F. N., Pinandito, A. M., & Lim, K. M. (2023) · Scientific Reports · doi:10.1038/s41598-023-29208-5 · Cited by 10
Whole-Genome Sequence and Interaction Analysis in the Production of Six Enzymes From the Three Bacillus Strains Present in a Commercial Direct-Fed Microbial (Norum™) Using a Bliss Independence Test
Hernández‐Patlan, D., Solís-Cruz, B., Latorre, J. D., Merino-Guzmán, R., Morales, M., Ausland, C., Hernández-Velasco, X., Holguin, O. O., Delgado, R., Hargis, B. M., et al. (2022) · Frontiers in Veterinary Science · doi:10.3389/fvets.2022.784387 · Cited by 10
“predicted responses (42, 43) and to identify synergistic, antagonistic, or additive effects (36, 37).”
Background
Transfer of IGF2BP3 Through Ara-C-Induced Apoptotic Bodies Promotes Survival of Recipient Cells
Gou, J., Li, H., Bi, J., Pang, X., Li, X., & Wang, Y. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.801226 · Cited by 10
“Half maximal inhibitory concentration (IC50) was calculated from survival curves by Bliss method (18).”
Method
Dual Disinfectants Synergistically Drive Adaptation and Evolution toward Higher Antimicrobial Resistance and Pathogenicity in Escherichia coli
Li, X., Yu, Z., Ye, J., Wang, X., Lin, H., Lei, L., Hu, W., & Luo, Y. (2025) · Environmental Science & Technology · doi:10.1021/acs.est.4c13071 · Cited by 9
Enhanced Antiproliferative Effect of Combined Treatment with Calcitriol and All-Trans Retinoic Acid in Relation to Vitamin D Receptor and Retinoic Acid Receptor α Expression in Osteosarcoma Cell Lines
Paukovčeková, S., Valík, D., Štěrba, J., & Veselská, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186591 · Cited by 9
“Analysis of possible interactions of compounds included in this study was performed using the Bliss independence model [65].”
Method
CD155 promotes radioresistance and malignancy of esophageal cancer by regulating Hippo-YAP pathway
Xin, H., Liu, Y., Chen, P., Yin, T., Wang, M., Liu, T., Wen, Z., & Cheng, Y. (2022) · Discover Oncology · doi:10.1007/s12672-022-00515-z · Cited by 10
“The interaction between radiation and CD155 knockdown was analyzed using the Bliss independence model [22].”
Method
Pandemic Response Box® library as a source of antifungal drugs against Scedosporium and Lomentospora species
Rollin‐Pinheiro, R., Xisto, M. I. D. D. S., de Castro-Almeida, Y., Rochetti, V. P., Borba-Santos, L. P., Fontes, Y. D. S., Ferreira‐Pereira, A., Rozental, S., & Barreto‐Bergter, E. (2023) · PLoS ONE · doi:10.1371/journal.pone.0280964 · Cited by 10
“Bliss independence model was performed according to Meletiadis and colleagues and Zhao and colleagues [32, 33].”
Method
Screening androgen receptor agonists of fish species using machine learning and molecular model in NORMAN water-relevant list
Long, X.-B., Yao, C.-R., Li, S., Zhang, J., Lu, Z., Ma, D.-D., Chen, C.-E., Ying, G., & Shi, W. (2024) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2024.133844 · Cited by 10
Inhibition of the Sec61 translocon overcomes cytokine‐induced glucocorticoid resistance in T‐cell acute lymphoblastic leukaemia
Meyer, L. K., Delgado-Martín, C., Sharp, P. P., Huang, B. J., McMinn, D. L., Vincent, T. L., Ryan, T. M., Horton, T. M., Wood, B. L., Teachey, D. T., et al. (2022) · British Journal of Haematology · doi:10.1111/bjh.18181 · Cited by 9
Enhanced cytotoxicity of a Pseudomonas Exotoxin A based immunotoxin against prostate cancer by addition of the endosomal escape enhancer SO1861
Masilamani, A. P., Huber, N., Nagl, C., Dettmer‐Monaco, V., Monaco, G., Wolf, I., Schultze-Seemann, S., Taromi, S., Gratzke, C., Fuchs, H., et al. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1211824 · Cited by 8
“The Bliss Independence Model was used to determine the Combination Index (CI) as a measure of synergism in cytotoxicity (Zhao et al., 2014).”
Method
Synergy of keratin peptides and natural oils embedded in nanostructured lipid carriers to protect and restore human hair structure
Reihani, N., & Ghourchian, H. (2025) · Journal of Molecular Liquids · doi:10.1016/j.molliq.2025.126957 · Cited by 11
Network-driven cancer cell avatars for combination discovery and biomarker identification for DNA damage response inhibitors
Papp, O., Jordán, V., Hetey, S., Balázs, R., Kaszás, V., Bartha, Á., Ordasi, N. N., Kamp, S., Farkas, B., Mettetal, J. T., et al. (2024) · npj Systems Biology and Applications · doi:10.1038/s41540-024-00394-w · Cited by 8
“Therearemultiplereasonswhy using the Bliss independence model is preferred over other alternative synergy modelslikeapplicabilityonentiredoserangesandincaseofnon-standard ornotavailabledose-responsecurves,straightforwardprobabilistic interpretation 83,84 .”
Method
Resistance to FOXM1 inhibitors in breast cancer is accompanied by impeding ferroptosis and apoptotic cell death
Kumar, S., Ziegler, Y., Plotner, B. N., Flatt, K. M., Kim, S. H., Katzenellenbogen, J. A., & Katzenellenbogen, B. S. (2024) · Breast Cancer Research and Treatment · doi:10.1007/s10549-024-07420-9 · Cited by 8
Multifunctional Nanoparticles as Radiosensitizers to Overcome Hypoxia-Associated Resistance in Cancer Radiotherapy
Chen, M., Yiu, H. P., Wang, Y.-C., Liu, T.-Y., & Li, C. (2024) · Nanomaterials · doi:10.3390/nano15010037 · Cited by 8
“A popular approach to test the synergistic effect of a drug combination is to examine an average response of different combined doses to see whether the response value exceeds the Bliss prediction [27,32–40].”
Hepatic toxicity induced by exposure to glyphosate/aminomethylphosphonic acid and oxytetracycline alone or in combination in zebrafish: A novel mechanism of the gut-liver axis.
Zheng, J.-Y., Wang, C., Teng, M.-M., Li, T., Jiang, J.-Z., Chen, X.-G., & Wu, F. (2026) · Aquatic Toxicology · doi:10.1016/j.aquatox.2026.107713 · Cited by 7
Synergy Between Pseudomonas aeruginosa Filtrates And Voriconazole Against Aspergillus fumigatus Biofilm Is Less for Mucoid Isolates From Persons With Cystic Fibrosis
Sass, G., Marsh, J. J., Shrestha, P., Sabino, R., & Stevens, D. A. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.817315 · Cited by 7
Structural and Functional Alterations Caused by Aureobasidin A in Clinical Resistant Strains of Candida spp.
Rollin‐Pinheiro, R., de Moraes, D., Bayona-Pacheco, B. L., Curvelo, J. A. D. R., dos Santos, G. M. P., Xisto, M. I. D. D. S., Borba-Santos, L. P., Rozental, S., Ferreira‐Pereira, A., & Barreto‐Bergter, E. (2023) · Journal of Fungi · doi:10.3390/jof9111115 · Cited by 7
“Bliss independence model was performed according to Meletiadis and colleagues and Zhao and colleagues [30,31].”
Method
Cooperative blockade of FLT3 and ALK synergistically suppresses growth of osteosarcoma
Zhang, W., Qi, L., Xu, H., Yin, C., Yu, Z., Xu, R., Feng, C., Ren, X., Tu, C., & Li, Z. (2024) · Oncogene · doi:10.1038/s41388-024-03205-y · Cited by 7
“The analysis and quanti ﬁ cation of the wound closure percentage were performed utilizing the Image J software.”
Synergy across the drugs approved for the treatment of asthma
ROGLIANI, P., RITONDO, B. L., Cavalli, F., GIORGINO, F. M., GIROLAMI, A., Gloria, P. A. N. E., PEZZUTO, G., ZERILLO, B., PUXEDDU, E., & Ora, J. (2022) · Minerva Medica · doi:10.23736/s0026-4806.21.07266-9 · Cited by 7
HSP70 Inhibition Blocks Adaptive Resistance and Synergizes with MEK Inhibition for the Treatment of NRAS-Mutant Melanoma
Parris, J. L. D., Barnoud, T., Leu, J. I.-J., Leung, J. C., Ma, W., Kirven, N. A., Poli, A. N. R., Kossenkov, A. V., Liu, Q., Salvino, J. M., et al. (2021) · Cancer Research Communications · doi:10.1158/2767-9764.crc-21-0033 · Cited by 7
“Synergy was determined using an interaction index calculated using a dose–response surface model based on the Bliss independence principle (27, 28).”
Dydrogesterone and levonorgestrel at environmentally relevant concentrations have antagonist effects with rhythmic oscillation in brain and eyes of zebrafish
Shi, W., Long, X.-B., Li, S., Ma, D.-D., Liu, F., Zhang, J., Lu, Z., & Ying, G. (2022) · Aquatic Toxicology · doi:10.1016/j.aquatox.2022.106177 · Cited by 7
Combination mTOR and SHP2 inhibitor treatment of lymphatic malformation endothelial cells
Wolter, J. K., Valencia-Sama, I., Osborn, A. J., Propst, E. J., Irwin, M. S., Papsin, B. C., & Wolter, N. E. (2022) · Microvascular Research · doi:10.1016/j.mvr.2022.104397 · Cited by 8
Selective cell cycle arrest in glioblastoma cell lines by quantum molecular resonance alone or in combination with temozolomide
Catanzaro, D., Milani, G., Bozza, A., Bernardi, M., Chieregato, K., Menarin, M., Merlo, A., Celli, P., Belli, R., Peroni, D., et al. (2022) · British Journal of Cancer · doi:10.1038/s41416-022-01865-9 · Cited by 7
“This model is indeed based on the probability of obtaining a determined effect [35].”
Background
Integrated proteomics identifies PARP inhibitor-induced prosurvival signaling changes as potential vulnerabilities in ovarian cancer
Deng, O., Dash, S., Nepomuceno, T. C., Fang, B., Yun, S. Y., Welsh, E. A., Lawrence, H. R., Marchion, D. C., Koomen, J. M., Monteiro, Á. N. A., et al. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102550 · Cited by 8
“Drug combination effects were assessed by the Bliss independence model (42).”
Method
Combining MEK and SRC inhibitors for treatment of colorectal cancer demonstrate increased efficacy in vitro but not in vivo
Fan, F., Ghosh, S., Powell, R. T., Roszik, J., Park, Y., Sobieski, M. M., Sorokin, A. V., STEPHAN, C. C., Kopetz, S., Ellis, L. M., et al. (2023) · PLoS ONE · doi:10.1371/journal.pone.0281063 · Cited by 8
“The theoretical additivity surface was then calculated using a Bliss independence model [40].”
Method
Heat shock factor 1 inhibition enhances the effects of modulated electro hyperthermia in a triple negative breast cancer mouse model
Viana, P. H. L., Schvarcz, C. A., Danics, L., Besztercei, B., Aloss, K., Bokhari, S. M. Z., Giunashvili, N., Bócsi, D., Koós, Z., Benyó, Z., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-57659-x · Cited by 7
“…the average of tumor masses for each treatment group (Sham + Vehicle: 300.0 mg, mEHT + Vehicle: 237.0 mg, Sham + KRIBB11: 312.3 mg, and mEHT + KRIBB11: 160.3 mg), we calacu-lated the expected combined effect based on individual mEHT and drug effects based on the Bliss Independence model 63,64 .”
MethodInfluential
The Synergistic Combination of Everolimus and Paroxetine Exerts Post-ischemic Neuroprotection In Vitro
Kumar, V. S. S., Pretorius, E., & Rajanikant, G. K. (2018) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-018-0605-6 · Cited by 7
Pseudomonas aeruginosa Virulence Factors Support Voriconazole Effects on Aspergillus fumigatus
Sass, G., Shrestha, P., & Stevens, D. A. (2021) · Pathogens · doi:10.3390/pathogens10050519 · Cited by 7
Wild-type TP53 defined gamma-secretase inhibitor sensitivity and synergistic activity with doxorubicin in GSCs.
Zhang, C., Martínez-Ledesma, E., Gao, F., Zhang, W., Ding, J., Wu, S., Li, X., Wu, J., Yuan, Y., Koul, D., et al. (2019) · PubMed Central · Cited by 7
Unleashing the synergistic effect of promising fungicides: a breakthrough solution for combating powdery mildew in pea plants
Maria, Naz, I., Khan, R., Alam, S. S., Iqbal, O., Akram, S., Rajput, N. A., Younas, M. U., Qasim, M., Ali, I., et al. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1448033 · Cited by 6
Antimigratory Effect of Lipophilic Cations Derived from Gallic and Gentisic Acid and Synergistic Effect with 5-Fluorouracil on Metastatic Colorectal Cancer Cells: A New Synthesis Route
Suárez-Rozas, C., Jara, J. A., Cortés, G., Rojas, D., Araya-Valdés, G., Molina‐Berríos, A., González‐Herrera, F., Fuentes-Retamal, S., Aránguiz, P., Campodónico, P. R., et al. (2024) · Cancers · doi:10.3390/cancers16172980 · Cited by 6
“For this article, the first model was used, a mathematical model appropriate for assessing the combined effect of two drugs with different mechanisms of action [20].”
Method
Predicting drug combination response surfaces
Huusari, R., Wang, T., Szedmák, S., Aittokallio, T. A., & Rousu, J. (2025) · npj Drug Discovery. · doi:10.1038/s44386-024-00004-z · Cited by 9
Tautomycin and enzalutamide combination yields synergistic effects on castration-resistant prostate cancer
Luo, M., Zhang, Y., Xu, Z., Wu, C., Ye, Y., Liu, R., Lv, S., & Wei, Q. (2022) · Cell Death Discovery · doi:10.1038/s41420-022-01257-1 · Cited by 6
“Two-way ANOVA tests, the bliss-independent model [40], and Chou-Talalay method [41] were used to determine the synergistic effect.”
Method
Targeting WEE1 kinase as a p53-independent therapeutic strategy in high-risk and relapsed acute lymphoblastic leukemia
Bell, H. L., Blair, H. J., Singh, M., Moorman, A. V., Heidenreich, O. T., van Delft, F. W., Lunec, J., & Irving, J. A. E. (2023) · Cancer Cell International · doi:10.1186/s12935-023-03057-8 · Cited by 6
“Drug combination effects were determined after 96 h, synergy scores were analyzed using the Bliss independence model [24, 25] and visualized using a Python script.”
Synergistic and Pharmacotherapeutic Effects of Gemcitabine and Cisplatin Combined Administration on Biliary Tract Cancer Cell Lines
Sakamoto, Y., Yamagishi, S., Okusaka, T., & Ojima, H. (2019) · Cells · doi:10.3390/cells8091026 · Cited by 6
Synergistic Effects of PARP Inhibition and Cholesterol Biosynthesis Pathway Modulation
Rutkowska, A., Eberl, H. C., Werner, T., Hennrich, M. L., Sévin, D. C., Petretich, M., Reddington, J. P., Pocha, S. M., Gade, S., Martinez-Segura, A., et al. (2024) · Cancer Research Communications · doi:10.1158/2767-9764.crc-23-0549 · Cited by 5
“The effects of combining niraparib or olaparib with either lipophilic (atorvastatin, fluvastatin) or hydrophilic (pravastatin) statins on a matrix of combination ranges were assessed using the Bliss Synergy Score (63).”
Intracellular Magnetic Nanodelivery of H 2 S and Heat Synergize to Reshape the Tumor Immune Microenvironment
Dai, L., Jiao, W., Li, J., He, Z., Lu, Q., Zheng, C., Li, H., Wang, S., Yan, B., Lv, Y., et al. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202501617 · Cited by 5
Host-targeted repurposed diltiazem enhances the antiviral activity of direct acting antivirals against Influenza A virus and SARS-CoV-2
Padey, B., Droillard, C., Dulière, V., Fouret, J., de Lamballerie, C. N., Milesi, C., Laurent, E., Brun, P., Traversier, A., Julien, T., et al. (2025) · Antiviral Research · doi:10.1016/j.antiviral.2025.106138 · Cited by 5
Polynucleotide Mixture Attenuates Ultraviolet B-Induced Skin Pigmentation
Oh, S., Jeon, H.-D., Rho, N., Son, K. H., & Byun, K. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26136399 · Cited by 6
“To determine whether the effect of PNM exceeds the combined effects of PN and AM, that is, to assess the presence of a synergistic effect when PN and AM are combined, we employed the Bliss independence model, which is widely used for evaluating drug synergy [49].”
Response envelope analysis for quantitative evaluation of drug combinations
Du, D., Chang, C.-H., Wang, Y., Tong, P., Chan, W., Chiu, Y., Peng, B., Tan, L., Weinstein, J. N., & Lorenzi, P. L. (2019) · Bioinformatics · doi:10.1093/bioinformatics/btz091 · Cited by 5
RRM2 is a target for synthetic lethal interactions with replication stress checkpoint addiction in high-risk neuroblastomaPreprint
Nunes, C., Depestel, L., Mus, L. M., Keller, K. M., Delhaye, L., Louwagie, A., Rishfi, M., Dolman, M. E. M., Olexiouk, V., Bartenhagen, C., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.11.25.397323 · Cited by 5
GPR15LG binds CXCR4 and synergistically modulates CXCL12-induced cell signaling and migration
Albers, D., Novikova, S., Vieyto‐Nuñez, J., Almeida‐Hernández, Y., Pastorio, C., Klassen, F., Weiss, D., von Maltitz, P., Jaikishan, J., Datta, M., et al. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02231-x · Cited by 4
“Values of 0 indicate no interaction, while negative values indicate antagonism and positive values synergistic effects [42].”
Synergistic transgenerational reproductive toxicity of polystyrene nanoplastics and butylparaben at NOAEL levels via SET-2–mediated H3K4me3 modification in Caenorhabditis elegans
Yu, C., Kuo, Y.-H., Chang, T.-T., & Liao, V. H. (2025) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2025.140499 · Cited by 4
Anticancer and apoptotic effects of orange peel extract and naringin on doxorubicin-induced apoptosis in human esophageal squamous carcinoma cell line
Tajaldini, M., Samadi, F., Asadi, J., Khosravi, A., & Samadi, F. (2025) · Pharmacological Research - Natural Products · doi:10.1016/j.prenap.2025.100244 · Cited by 4
“To explain the combination therapies, a combination index (CI) based on the effective doses obtained by IC 50 was calculated according to the following equation [12]: CI= Where, C A,X and C B,x are the concentrations of drug A and B used in combination to achieve x% drug effect.”
Novel two‐tiered screening approach identifies synergistic combinations of natural compounds for prostate cancer prevention and treatment
Friedman, C. A., Saha, A., Hackman, G. L., Lu, X., Lodi, A., Tiziani, S., & DiGiovanni, J. (2024) · Molecular Carcinogenesis · doi:10.1002/mc.23674 · Cited by 4
“22 No samples or animals were excluded from the reported analysis.”
Background
Triple Combination of Entinostat, a Bromodomain Inhibitor, and Cisplatin Is a Promising Treatment Option for Bladder Cancer
Bollmann, L. M., Lange, F., Hamacher, A., Biermann, L., Schäker‐Hübner, L., Hansen, F. K., & Kassack, M. U. (2024) · Cancers · doi:10.3390/cancers16193374 · Cited by 4
“Data were analyzed according to Chou-Talalay [57] (Table 3) and according to the Bliss model [58] (Figure 3).”
Method
A Quantitative Systems Pharmacology Approach to Infer Pathways Involved in Complex Disease Phenotypes
Schurdak, M. E., Pei, F., Lezon, T. R., Carlisle, D. L., Friedlander, R. M., Taylor, D. L., & Stern, A. M. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7847-2_16 · Cited by 4
The polyamine transporter ATP13A3 mediates DFMO-induced polyamine uptake in neuroblastomaPreprint
Azfar, M., Gao, W., den Haute, C. V., Xiao, L., Karsa, M., Pandher, R., Ronca, E., Bongers, A., Karsa, A., Spurling, D., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.02.20.581161 · Cited by 4
Detecting bliss synergy in in vivo combination studies with a tumor kinetic model
Zhao, W., Vicini, P., Novick, S., Anderton, J., Davies, G., DAngelo, G., O'Day, T., Yu, B., Harper, J., Narwal, R., et al. (2019) · Pharmaceutical Statistics · doi:10.1002/pst.1952 · Cited by 4
“I t ð Þ 1⁄4 yAB t ð Þ − yA t ð Þ − yB t ð Þ þ yA t ð Þ*yB t ð Þ (5)”
Self-citation
Nanocellulose synthesis via synergistic application of solid acid and cellulase
Dong, S. H., Tan, C., Zhang, Y., Gan, L., Ruan, R. R., Dai, L., Wang, Y., Huo, E., Jiang, Q., Zhao, Y., et al. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.139158 · Cited by 3
Preventing Preterm Birth: The Search for Tocolytic Synergism
Hossain, M. R., Paul, M., Tolosa, J. M., Smith, R., & Paúl, J. (2025) · Reproductive Sciences · doi:10.1007/s43032-025-01941-4 · Cited by 3
“The HSA and Bliss Independence models follow an effect-based strategy that compares the effect of a combination (observed response) directly to the effects of its constituent drugs (expected additive effect), which con - stitutes efficacy-driven synergy [ 38, 39, 43].”
Synergistic effect of dual-biowax on biodegradable PLA nanofibers for high-performance and antifouling oil–water separation: Mechanistic insights from molecular docking and dynamics simulations
Soni, N., Jaiswal, M., Choudhury, M., Chauhan, H. A., Kumeria, T., & Nayak, R. (2026) · Chemical Engineering Journal · doi:10.1016/j.cej.2026.177933 · Cited by 3
A comparative study of in vitro dose–response estimation under extreme observations
Fang, X., & Zhou, S. (2023) · Biometrical Journal · doi:10.1002/bimj.202200092 · Cited by 4
“Robust estimation of the dose–response curve can play a critical role in the investigation of adequate drug combinations (García-Fuente et al., 2018; Lee et al., 2007; Zhao et al., 2014).”
Background
Hsp70‐Bim incoherent feedforward loop contributes to cell‐fate heterogeneity and fractional killing
Yin, F., Song, T., Wang, Z., Liu, J., Zhang, H., Tang, Y., & Zhang, Z. (2023) · British Journal of Pharmacology · doi:10.1111/bph.16245 · Cited by 3
Targeting Heat Shock Transcription Factor 4 Enhances the Efficacy of Cabozantinib and Immune Checkpoint Inhibitors in Renal Cell Carcinoma
Saito, S., Yoshino, H., Yokoyama, S., Tominaga, M., Li, G., Arima, J., Kawahara, I., Fukuda, I., Mitsuke, A., Sakaguchi, T., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26041776 · Cited by 3
Bioactives in Disease Prevention and Health Promotion: Exploiting Combinatorial Effects
Gurumallu, S. C., & Javaraiah, R. (2020) · Current Bioactive Compounds · doi:10.2174/1573407216999200612103526 · Cited by 3
SynDISCO: A Mechanistic Modeling-Based Framework for Predictive Prioritization of Synergistic Drug Combinations Targeting Cell Signalling Networks
Shin, S., & Nguyen, L. K. (2023) · Methods in molecular biology · doi:10.1007/978-1-0716-3008-2_17 · Cited by 3
Enhancing efficacy of the MEK inhibitor trametinib with paclitaxel in KRAS -mutated colorectal cancer
Ghosh, S., Fan, F., Powell, R. T., Park, Y. S., STEPHAN, C. C., Kopetz, S., Ellis, L. M., & Bhattacharya, R. (2024) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359241303302 · Cited by 4
“31 By comparing the empirically determined drug effect to the Bliss independence model, the interactions between each pair of drugs were characterized as antagonistic, additive, or synergistic.”
Synergy Assessment for Plant Growth by Independent Joint Action Theory
Huang, Z., & Falco, K. A. (2021) · HortScience · doi:10.21273/hortsci15731-21 · Cited by 3
“Bliss’s Independent Joint Action theory is also regarded as a particularly important alternative to Loewe Additivity in pharmacological research (Zhao et al., 2014).”
Background

Authors: Zhao, W., Sachsenmeier, K., Zhang, L., Sult, E., Hollingsworth, R. E., & Yang, H.
Affiliations: AbbVie (United States) (US)
Corresponding author: Zhao, Wei
ORCID: Zhao, Wei
Sachsenmeier, Kris
Zhang, Lanju
Hollingsworth, Robert E.
Yang, Harry
Venue: SLAS Discovery
Publisher: Elsevier BV
Published: 2014-06
Volume: 19
Issue: 5
Pages: 817-821
ISSN: 2472-5552 (ISSN-L)
DOI: 10.1177/1087057114521867
OpenAlex: W1980181290
Cited by: 322
References: 14
Citations by year: 2026: 46 · 2025: 33 · 2024: 29 · 2023: 45 · 2022: 40 · 2021: 19 · 2020: 26 · 2019: 23 · 2018: 17 · 2017: 17 · 2016: 14 · 2015: 11 · 2014: 2
FWCI: 15.18
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor, 2866 d)
Locations: SLAS DISCOVERY (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
Social Sciences › Decision Sciences › Management Science and Operations Research › Optimal Experimental Design Methods
Keywords: Bliss independence model, drug synergy, drug-drug interactions, false positive reduction, epidermal growth factor receptor, IGF-1 receptor, drug combination screening
MeSH terms: Algorithms, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Dose-Response Relationship, Drug, Drug Combinations, Drug Interactions, Drug Synergism, Humans, Lung Neoplasms, Models, Chemical, Neoplasms, Regression Analysis, Technology, Pharmaceutical, Signal Transduction, Receptor, IGF Type 1, Drug Resistance, Neoplasm, ErbB Receptors

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

A New Bliss Independence Model to Analyze Drug Combination Data

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks