Details of the Drug Combination

General Information of Drug Combination (ID: DCKOTM9)

• Drug Combination Name: Erlotinib + SCH-900776
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Erlotinib (DMCMBHA): Small molecular drug
  SCH-900776 (DM67EMK): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HT29
  Zero Interaction Potency (ZIP) Score: 2.03
  Bliss Independence Score: 6.04
  Loewe Additivity Score: 8.28
  LHighest Single Agent (HSA) Score: 11.16

Molecular Interaction Atlas of This Drug Combination

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	[5]

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	[6]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[7]

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	[8]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[9]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[9]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[9]

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	[10]

Indication(s) of SCH-900776

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 2	[4]

SCH-900776 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Checkpoint kinase-1 (CHK1)	TTTU902	CHK1_HUMAN	Inhibitor	[11]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCF8BZU	OVCAR3	Investigative	[1]
Adenocarcinoma	DCTTDP0	CAOV3	Investigative	[1]
Adenocarcinoma	DC2XL6A	A427	Investigative	[1]
Adenocarcinoma	DCIKKKF	NCIH2122	Investigative	[1]
Adenocarcinoma	DCU81XR	NCIH23	Investigative	[1]
Adenocarcinoma	DCXFE85	NCIH520	Investigative	[1]
Adenocarcinoma	DCKX7YD	COLO320DM	Investigative	[1]
Adenocarcinoma	DCX7EJU	DLD1	Investigative	[1]
Adenocarcinoma	DCQ2UF3	SW-620	Investigative	[1]
Adenocarcinoma	DC9GKCF	HCT116	Investigative	[1]
Amelanotic melanoma	DCVPQTS	A2058	Investigative	[1]
Germ cell tumour	DC7UZV4	PA1	Investigative	[1]
Malignant melanoma	DCEKLJP	HT144	Investigative	[1]
Malignant melanoma	DCXLZSI	RPMI7951	Investigative	[1]
Malignant melanoma	DCW6E16	SKMEL30	Investigative	[1]
Malignant melanoma	DCA2ZYO	UACC62	Investigative	[1]
Malignant melanoma	DCP2AOX	A375	Investigative	[1]
Mesothelioma	DCXZ5EZ	MSTO	Investigative	[1]
Non small cell carcinoma	DCTS95G	SKMES1	Investigative	[1]
Ovarian endometrioid adenocarcinoma	DC0OQIR	A2780	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCXIX79	SK-OV-3	Investigative	[1]
Prostate carcinoma	DCNLBJK	LNCAP	Investigative	[1]
Carcinoma	DCMBPBM	OV90	Investigative	[12]
Carcinoma	DCK7YBM	EFM192B	Investigative	[12]
Rectal adenocarcinoma	DCE0BDL	SW837	Investigative	[12]

References

• [1] 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.
• [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] 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: 7943).
• [5] Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
• [6] 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.
• [7] Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy. Adv Drug Deliv Rev. 2009 Jan 31;61(1):26-33.
• [8] 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.
• [9] Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706.
• [10] 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.
• [11] Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening. Mol Cancer Ther. 2011 Apr;10(4):591-602.
• [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.