Details of the Drug Combination

General Information of Drug Combination (ID: DCG0R6M)

• Drug Combination Name: Taxol + Erlotinib
• Indication: Malignant melanoma; Status: Investigative [1]
• Component Drugs:
  Taxol (DMUOT9V): Small molecular drug
  Erlotinib (DMCMBHA): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: UACC62
  Zero Interaction Potency (ZIP) Score: 3.53
  Bliss Independence Score: 3.43
  Loewe Additivity Score: 7.03
  LHighest Single Agent (HSA) Score: 9.82

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Taxol

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Pancreatic cancer	2C10	Phase 3	[4]
Gastric adenocarcinoma	2B72	Phase 2	[5]
Ovarian cancer	2C73	Phase 2	[5]

Taxol Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Apoptosis regulator Bcl-2 (BCL-2)	TTJGNVC	BCL2_HUMAN	Modulator	[2]
Tubulin beta (TUBB)	TTYFKSZ	NOUNIPROTAC	Modulator	[2]

Indication(s) of Erlotinib

Disease Entry	ICD 11	Status	REF
Adrenal gland neoplasm	N.A.	Approved	[6]
Adult hepatocellular carcinoma	N.A.	Approved	[6]
Brain cancer	2A00	Approved	[6]
Esophageal disorder	N.A.	Approved	[6]
Lung cancer	2C25.0	Approved	[6]
Non-small-cell lung cancer	2C25.Y	Approved	[7]
Pancreatic adenocarcinoma	N.A.	Approved	[6]
Psoriasis	EA90	Approved	[6]
Salivary gland squamous cell carcinoma	N.A.	Approved	[6]
Pancreatic cancer	2C10	Phase 3	[7]
Colon cancer	2B90.Z	Phase 2	[7]
Ependymoma	2A00.0Y	Investigative	[6]
Neoplastic meningitis	N.A.	Investigative	[6]
Neuroblastoma	2D11.2	Investigative	[6]

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	[8]

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	[9]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[10]

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	[11]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[12]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[12]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[12]

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	[13]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast carcinoma	DCX0DJT	OCUBM	Investigative	[14]
Carcinoma	DCRGN7E	EFM192B	Investigative	[14]
Adenocarcinoma	DC9LWZ4	CAOV3	Investigative	[1]
Adenocarcinoma	DCJE5QM	OVCAR3	Investigative	[1]
Adenocarcinoma	DCH27YA	NCIH2122	Investigative	[1]
Adenocarcinoma	DC5VT3P	NCIH520	Investigative	[1]
Adenocarcinoma	DCCVPFR	COLO320DM	Investigative	[1]
Adenocarcinoma	DCIH7G3	DLD1	Investigative	[1]
Adenocarcinoma	DCUDDK0	HT29	Investigative	[1]
Adenocarcinoma	DC01B5H	SW-620	Investigative	[1]
Germ cell tumour	DCX8RE7	PA1	Investigative	[1]
Large cell lung carcinoma	DCF7ZHQ	NCI-H460	Investigative	[1]
Malignant melanoma	DCJA82X	A375	Investigative	[1]
Malignant melanoma	DCUV740	HT144	Investigative	[1]
Malignant melanoma	DCCK40Q	RPMI7951	Investigative	[1]
Malignant melanoma	DCAZ60S	SKMEL30	Investigative	[1]
Mesothelioma	DCPWGK0	MSTO	Investigative	[1]
Non small cell carcinoma	DC8EXCJ	SKMES1	Investigative	[1]
Ovarian endometrioid adenocarcinoma	DCOGBJH	A2780	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCH2AY4	SK-OV-3	Investigative	[1]

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] Paclitaxel directly binds to Bcl-2 and functionally mimics activity of Nur77. Cancer Res. 2009 Sep 1;69(17):6906-14.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Erlotinib FDA Label
• [7] 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).
• [8] Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
• [9] 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.
• [10] Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy. Adv Drug Deliv Rev. 2009 Jan 31;61(1):26-33.
• [11] 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.
• [12] Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706.
• [13] 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.
• [14] 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.