Details of the Drug Combination

General Information of Drug Combination (ID: DC3VAAH)

Drug Combination Name
Erlotinib MK-4827
Indication
Disease Entry Status REF
Carcinoma Investigative [1]
Component Drugs Erlotinib   DMCMBHA MK-4827   DMLYGH4
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: EFM192B
Zero Interaction Potency (ZIP) Score: 11.31
Bliss Independence Score: 11.48
Loewe Additivity Score: 15.56
LHighest Single Agent (HSA) Score: 17.26

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Erlotinib
Disease Entry ICD 11 Status REF
Adrenal gland neoplasm N.A. Approved [2]
Adult hepatocellular carcinoma N.A. Approved [2]
Brain cancer 2A00 Approved [2]
Esophageal disorder N.A. Approved [2]
Lung cancer 2C25.0 Approved [2]
Non-small-cell lung cancer 2C25.Y Approved [3]
Pancreatic adenocarcinoma N.A. Approved [2]
Psoriasis EA90 Approved [2]
Salivary gland squamous cell carcinoma N.A. Approved [2]
Pancreatic cancer 2C10 Phase 3 [3]
Colon cancer 2B90.Z Phase 2 [3]
Ependymoma 2A00.0Y Investigative [2]
Neoplastic meningitis N.A. Investigative [2]
Neuroblastoma 2D11.2 Investigative [2]
Erlotinib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Inhibitor [6]
------------------------------------------------------------------------------------
Erlotinib Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [8]
------------------------------------------------------------------------------------
Erlotinib Interacts with 4 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [10]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [10]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [10]
------------------------------------------------------------------------------------
Erlotinib Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Increases Response [11]
------------------------------------------------------------------------------------
Indication(s) of MK-4827
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 3 [4]
Breast cancer 2C60-2C65 Phase 2 [5]
Ewing sarcoma 2B52 Phase 1 [5]
MK-4827 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Poly [ADP-ribose] polymerase (PARP) TTEBCY8 NOUNIPROTAC Modulator [12]
------------------------------------------------------------------------------------
MK-4827 Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [13]
Carboxylesterase 1 (CES1) DEB30C5 EST1_HUMAN Metabolism [14]
Beta-glucuronidase (GUSB) DEP54UE BGLR_HUMAN Metabolism [14]
------------------------------------------------------------------------------------
MK-4827 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [15]
------------------------------------------------------------------------------------

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adenocarcinoma DC03QIJ CAOV3 Investigative [16]
Adenocarcinoma DCGH1IE OVCAR3 Investigative [16]
Adenocarcinoma DCJMO4P A427 Investigative [16]
Adenocarcinoma DCUH9VF NCIH2122 Investigative [16]
Adenocarcinoma DC19XR0 NCIH23 Investigative [16]
Adenocarcinoma DCG54VV NCIH520 Investigative [16]
Adenocarcinoma DC5Y81L COLO320DM Investigative [16]
Adenocarcinoma DCL2ANL DLD1 Investigative [16]
Adenocarcinoma DCJTYT7 HCT116 Investigative [16]
Adenocarcinoma DC0W83Z HT29 Investigative [16]
Adenocarcinoma DC5FCN9 SW-620 Investigative [16]
Amelanotic melanoma DCN9VS2 A2058 Investigative [16]
Ewing sarcoma-peripheral primitive neuroectodermal tumour DCM6AE4 ES2 Investigative [16]
Germ cell tumour DCH02J5 PA1 Investigative [16]
Large cell lung carcinoma DC0VV6K NCI-H460 Investigative [16]
Malignant melanoma DCHEDY8 A375 Investigative [16]
Malignant melanoma DC3POQE HT144 Investigative [16]
Malignant melanoma DCG0M5A RPMI7951 Investigative [16]
Malignant melanoma DCZ8NAS SKMEL30 Investigative [16]
Malignant melanoma DCTFYGE UACC62 Investigative [16]
Non small cell carcinoma DC4R5XF SKMES1 Investigative [16]
Ovarian endometrioid adenocarcinoma DC011UA A2780 Investigative [16]
Ovarian serous cystadenocarcinoma DCVUA20 SK-OV-3 Investigative [16]
Prostate carcinoma DC98K69 LNCAP Investigative [16]
Breast and ovarian cancer syndrome DCG60RJ UWB1289+BRCA1 Investigative [1]
Breast carcinoma DCKE86M KPL1 Investigative [1]
Breast carcinoma DCWNPQ6 OCUBM Investigative [1]
Carcinoma DCXXSJO OV90 Investigative [1]
Colon adenocarcinoma DCZANBO LOVO Investigative [1]
Colon carcinoma DCGQRYB RKO Investigative [1]
Invasive ductal carcinoma DCLC4QF T-47D Investigative [1]
Rectal adenocarcinoma DCNS45Z SW837 Investigative [1]
------------------------------------------------------------------------------------
⏷ Show the Full List of 32 DrugCom(s)

References

1 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.
2 Erlotinib FDA Label
3 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4920).
4 ClinicalTrials.gov (NCT03602859) A Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer (FIRST). U.S. National Institutes of Health.
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
7 Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on erlotinib hydrochloride (Tarceva) disposition in in vitro and in vivo pharmacokinetic studies employing Bcrp1-/-/Mdr1a/1b-/- (triple-knockout) and wild-type mice. Mol Cancer Ther. 2008 Aug;7(8):2280-7.
8 Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy. Adv Drug Deliv Rev. 2009 Jan 31;61(1):26-33.
9 In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug Metab Dispos. 2014 Jul;42(7):1202-9.
10 Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706.
11 Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004 May 20;350(21):2129-39. doi: 10.1056/NEJMoa040938. Epub 2004 Apr 29.
12 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
13 Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. J Med Chem. 2009 Nov 26;52(22):7170-85.
14 Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
15 Autophagy up-regulated by MEK/ERK promotes the repair of DNA damage caused by aflatoxin B1. Toxicol Mech Methods. 2022 Feb;32(2):87-96. doi: 10.1080/15376516.2021.1968985. Epub 2021 Aug 26.
16 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.