Details of the Drug Combination

General Information of Drug Combination (ID: DCIU4WO)

• Drug Combination Name: Vemurafenib + Terameprocol
• Indication: Glioma; Status: Investigative [1]
• Component Drugs:
  Vemurafenib (DM62UG5): Small molecular drug
  Terameprocol (DMC3P45): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SF-268
  Zero Interaction Potency (ZIP) Score: 3.75
  Bliss Independence Score: 8.99
  Loewe Additivity Score: 6.44
  LHighest Single Agent (HSA) Score: 5.88

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Vemurafenib

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Approved	[2]

Vemurafenib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase B-raf (BRAF)	TTWCGQT	BRAF_HUMAN	Modulator	[6]

Vemurafenib Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[8]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[8]

Vemurafenib Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]

Vemurafenib Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Microphthalmia-associated transcription factor (MITF)	OT6XJCZH	MITF_HUMAN	Affects Expression	[4]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[10]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[11]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[5]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[5]
CD70 antigen (CD70)	OTHB2AL1	CD70_HUMAN	Decreases Expression	[12]
Melanocyte protein PMEL (PMEL)	OTCDDHHM	PMEL_HUMAN	Increases Expression	[4]
Melanoma antigen recognized by T-cells 1 (MLANA)	OT1N2S2K	MAR1_HUMAN	Increases Expression	[4]

Indication(s) of Terameprocol

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]

Terameprocol Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Transcription factor Sp1 (SP1)	TTZEP6S	SP1_HUMAN	Modulator	[3]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Carcinoma	DC6RUMA	MCF7	Investigative	[13]
Colon carcinoma	DC6Y6IU	KM12	Investigative	[13]
Invasive ductal carcinoma	DCY6P8D	HS 578T	Investigative	[13]
Invasive ductal carcinoma	DCX50SK	BT-549	Investigative	[13]
Adenocarcinoma	DCRQR3H	DU-145	Investigative	[1]
Adenocarcinoma	DCLE032	OVCAR3	Investigative	[1]
Adenocarcinoma	DCJEAXE	NCIH23	Investigative	[1]
Adenocarcinoma	DCWZDJQ	HCT-15	Investigative	[1]
Adenocarcinoma	DCXMIGI	HCT116	Investigative	[1]
Adult acute myeloid leukemia	DCM9RZ0	HL-60(TB)	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCNXUP5	MOLT-4	Investigative	[1]
Glioblastoma	DCZDZK9	SNB-75	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCXHJG4	OVCAR-5	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC0UZ9T	OVCAR-4	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCIZWUD	NCI\\/ADR-RES	Investigative	[1]
Lung adenocarcinoma	DCQXBOS	MDA-MB-231	Investigative	[1]
Lung adenocarcinoma	DCCANZU	EKVX	Investigative	[1]
Lung adenocarcinoma	DCZO15L	NCI-H522	Investigative	[1]
Melanoma	DC3GULW	SK-MEL-2	Investigative	[1]
Non-small cell lung carcinoma	DC5YRXJ	HOP-92	Investigative	[1]
Prostate carcinoma	DCUZN1R	PC-3	Investigative	[1]
Renal cell carcinoma	DCRNDL8	SN12C	Investigative	[1]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
• [2] 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: 5893).
• [3] Terameprocol, a novel site-specific transcription inhibitor with anticancer activity. IDrugs. 2008 Mar;11(3):204-14.
• [4] PLX4032 Mediated Melanoma Associated Antigen Potentiation in Patient Derived Primary Melanoma Cells. J Cancer. 2015 Oct 29;6(12):1320-30. doi: 10.7150/jca.11126. eCollection 2015.
• [5] Actin remodeling confers BRAF inhibitor resistance to melanoma cells through YAP/TAZ activation. EMBO J. 2016 Mar 1;35(5):462-78. doi: 10.15252/embj.201592081. Epub 2015 Dec 14.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [7] Differential effects of the oncogenic BRAF inhibitor PLX4032 (vemurafenib) and its progenitor PLX4720 on ABCB1 function. J Pharm Pharm Sci. 2014;17(1):154-68.
• [8] Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
• [9] Vemurafenib for the treatment of melanoma. Expert Opin Pharmacother. 2012 Dec;13(17):2533-43.
• [10] Perturbation biology nominates upstream-downstream drug combinations in RAF inhibitor resistant melanoma cells. Elife. 2015 Aug 18;4:e04640. doi: 10.7554/eLife.04640.
• [11] Overcoming melanoma resistance to vemurafenib by targeting CCL2-induced miR-34a, miR-100 and miR-125b. Oncotarget. 2016 Jan 26;7(4):4428-41. doi: 10.18632/oncotarget.6599.
• [12] Melanoma Expressed-CD70 Is Regulated by RhoA and MAPK Pathways without Affecting Vemurafenib Treatment Activity. PLoS One. 2016 Feb 1;11(2):e0148095. doi: 10.1371/journal.pone.0148095. eCollection 2016.
• [13] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165