Details of the Drug Combination

General Information of Drug Combination (ID: DCKP6B0)

• Drug Combination Name: Vemurafenib + Valrubicin
• Indication: Lung adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Vemurafenib (DM62UG5): Small molecular drug
  Valrubicin (DMOYJFK): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HOP-62
  Zero Interaction Potency (ZIP) Score: 0.3
  Bliss Independence Score: 7.08
  Loewe Additivity Score: 5.7
  LHighest Single Agent (HSA) Score: 5.74

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	[5]

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	[8]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[9]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[9]

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	[10]

Vemurafenib Interacts with 19 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Microphthalmia-associated transcription factor (MITF)	OT6XJCZH	MITF_HUMAN	Affects Expression	[6]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[11]
Cyclin-dependent kinase 4 (CDK4)	OT7EP05T	CDK4_HUMAN	Decreases Expression	[12]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[13]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[12]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[7]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[7]
CD70 antigen (CD70)	OTHB2AL1	CD70_HUMAN	Decreases Expression	[14]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[12]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Decreases Expression	[15]
Melanocyte protein PMEL (PMEL)	OTCDDHHM	PMEL_HUMAN	Increases Expression	[6]
Melanoma-associated antigen 1 (MAGEA1)	OTXAO193	MAGA1_HUMAN	Decreases Expression	[6]
Thyroxine 5-deiodinase (DIO3)	OTNTITOT	IOD3_HUMAN	Decreases Expression	[16]
Melanoma antigen recognized by T-cells 1 (MLANA)	OT1N2S2K	MAR1_HUMAN	Increases Expression	[6]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[13]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Affects Response To Substance	[17]
Serine/threonine-protein kinase B-raf (BRAF)	OT7S81XQ	BRAF_HUMAN	Increases Response To Substance	[18]
Heat shock 70 kDa protein 1A (HSPA1A)	OTKGIE76	HS71A_HUMAN	Decreases Response To Substance	[19]
GTPase NRas (NRAS)	OTVQ1DG3	RASN_HUMAN	Affects Response To Substance	[17]

Indication(s) of Valrubicin

Disease Entry	ICD 11	Status	REF
Bladder cancer	2C94	Approved	[3]
In situ carcinoma	N.A.	Approved	[4]
Urinary bladder cancer	N.A.	Approved	[4]
Psoriasis vulgaris	EA90	Phase 2	[5]

Valrubicin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Inhibitor	[20]

Valrubicin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[21]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast adenocarcinoma	DC357L4	MDA-MB-468	Investigative	[22]
Colon adenocarcinoma	DC9DTJU	COLO 205	Investigative	[22]
Invasive ductal carcinoma	DC1MEII	T-47D	Investigative	[22]
Invasive ductal carcinoma	DC9PF3Y	BT-549	Investigative	[22]
Invasive ductal carcinoma	DC39B6D	HS 578T	Investigative	[22]
Adenocarcinoma	DC58HRN	HT29	Investigative	[1]
Adult acute myeloid leukemia	DC38X64	HL-60(TB)	Investigative	[1]
Amelanotic melanoma	DCMQFCW	MDA-MB-435	Investigative	[1]
Amelanotic melanoma	DCHKPDP	M14	Investigative	[1]
Anaplastic large cell lymphoma	DCB5B60	SR	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCCOGH2	CCRF-CEM	Investigative	[1]
Clear cell renal cell carcinoma	DCTZ2YQ	A498	Investigative	[1]
Clear cell renal cell carcinoma	DCTU84S	TK-10	Investigative	[1]
Clear cell renal cell carcinoma	DC7I4O5	CAKI-1	Investigative	[1]
Cutaneous melanoma	DC29OJS	SK-MEL-5	Investigative	[1]
Cutaneous melanoma	DCE42W4	SK-MEL-28	Investigative	[1]
Glioblastoma	DC5QEY2	SNB-75	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCTINME	OVCAR-8	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCNUTPF	NCI\\/ADR-RES	Investigative	[1]
Malignant melanoma	DCHVQU8	LOX IMVI	Investigative	[1]
Melanoma	DC1XRDQ	MALME-3M	Investigative	[1]
Melanoma	DCN80NH	UACC-257	Investigative	[1]
Melanoma	DC8KN7T	SK-MEL-2	Investigative	[1]
Non-small cell lung carcinoma	DCB1US3	HOP-92	Investigative	[1]
Papillary renal cell carcinoma	DCR8A84	ACHN	Investigative	[1]
Plasma cell myeloma	DCSXUYR	RPMI-8226	Investigative	[1]
Pleural epithelioid mesothelioma	DCJ45H4	NCI-H226	Investigative	[1]
Renal cell carcinoma	DCSUUFW	UO-31	Investigative	[1]

References

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• [4] Valrubicin FDA Label
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• [19] HSP70 Inhibition Limits FAK-Dependent Invasion and Enhances the Response to Melanoma Treatment with BRAF Inhibitors. Cancer Res. 2016 May 1;76(9):2720-30. doi: 10.1158/0008-5472.CAN-15-2137. Epub 2016 Mar 16.
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