General Information of Drug Combination (ID: DCS3U2A)

Drug Combination Name
MK-5108 Erlotinib
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs MK-5108   DMFGYKS Erlotinib   DMCMBHA
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: HT29
Zero Interaction Potency (ZIP) Score: 1.38
Bliss Independence Score: 9.07
Loewe Additivity Score: 7.13
LHighest Single Agent (HSA) Score: 10.06

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of MK-5108
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [2]
MK-5108 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aurora kinase B (AURKB) TT5LS6T AURKB_HUMAN Inhibitor [5]
Aurora kinase A (AURKA) TTPS3C0 AURKA_HUMAN Inhibitor [5]
------------------------------------------------------------------------------------
Indication(s) of Erlotinib
Disease Entry ICD 11 Status REF
Adrenal gland neoplasm N.A. Approved [3]
Adult hepatocellular carcinoma N.A. Approved [3]
Brain cancer 2A00 Approved [3]
Esophageal disorder N.A. Approved [3]
Lung cancer 2C25.0 Approved [3]
Non-small-cell lung cancer 2C25.Y Approved [4]
Pancreatic adenocarcinoma N.A. Approved [3]
Psoriasis EA90 Approved [3]
Salivary gland squamous cell carcinoma N.A. Approved [3]
Pancreatic cancer 2C10 Phase 3 [4]
Colon cancer 2B90.Z Phase 2 [4]
Ependymoma 2A00.0Y Investigative [3]
Neoplastic meningitis N.A. Investigative [3]
Neuroblastoma 2D11.2 Investigative [3]
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]
------------------------------------------------------------------------------------

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Breast and ovarian cancer syndrome DCOBHS3 UWB1289 Investigative [12]
Breast and ovarian cancer syndrome DCS8BJ2 UWB1289+BRCA1 Investigative [12]
Breast carcinoma DCFUGT7 KPL1 Investigative [12]
Breast carcinoma DCIC8RS OCUBM Investigative [12]
Carcinoma DCDD06T EFM192B Investigative [12]
Colon adenocarcinoma DCN4N4F LOVO Investigative [12]
Colon carcinoma DC3MKVG RKO Investigative [12]
Invasive ductal carcinoma DCTE8LK T-47D Investigative [12]
Rectal adenocarcinoma DCI88SZ SW837 Investigative [12]
Adenocarcinoma DCM4Q20 OVCAR3 Investigative [1]
Adenocarcinoma DC1ZH7A CAOV3 Investigative [1]
Adenocarcinoma DCLHP24 A427 Investigative [1]
Adenocarcinoma DCG37J1 NCIH1650 Investigative [1]
Adenocarcinoma DCPXROO NCIH2122 Investigative [1]
Adenocarcinoma DC76B4I NCIH23 Investigative [1]
Adenocarcinoma DC5TJ1Q NCIH520 Investigative [1]
Adenocarcinoma DCYSN5X COLO320DM Investigative [1]
Adenocarcinoma DCK4QKP DLD1 Investigative [1]
Adenocarcinoma DCKVT7V SW-620 Investigative [1]
Adenocarcinoma DCXAF9D HCT116 Investigative [1]
Amelanotic melanoma DCIO91C A2058 Investigative [1]
Germ cell tumour DCBZQZR PA1 Investigative [1]
Large cell lung carcinoma DC1OL2T NCI-H460 Investigative [1]
Malignant melanoma DCX2EF7 HT144 Investigative [1]
Malignant melanoma DCKGI43 RPMI7951 Investigative [1]
Malignant melanoma DCQV03K SKMEL30 Investigative [1]
Malignant melanoma DCVANOK UACC62 Investigative [1]
Malignant melanoma DC4KM6B A375 Investigative [1]
Mesothelioma DCR914L MSTO Investigative [1]
Ovarian endometrioid adenocarcinoma DC51XGC A2780 Investigative [1]
Ovarian serous cystadenocarcinoma DCA4D1Y SK-OV-3 Investigative [1]
Prostate carcinoma DC0PT5I LNCAP Investigative [1]
Prostate carcinoma DCEATRI VCAP Investigative [1]
------------------------------------------------------------------------------------
⏷ Show the Full List of 33 DrugCom(s)

References

1 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
2 ClinicalTrials.gov (NCT00543387) Treatment of Participants With Advanced and/or Refractory Solid Tumors (MK-5108-001 AM4). U.S. National Institutes of Health.
3 Erlotinib FDA Label
4 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).
5 A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
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 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.