Details of the Drug Combination

General Information of Drug Combination (ID: DCYF5KP)

Drug Combination Name

SNX-2112 10-hydroxycamptothecin

Indication

Disease Entry	Status	REF
Breast and ovarian cancer syndrome	Investigative	[1]

Component Drugs

SNX-2112 DMB5A80

10-hydroxycamptothecin DM9WLN4

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: UWB1289+BRCA1

Zero Interaction Potency (ZIP) Score: 3.21

Bliss Independence Score: 8.74

Loewe Additivity Score: 8.37

LHighest Single Agent (HSA) Score: 9.58

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of SNX-2112

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[2]

SNX-2112 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Heat shock protein 90 alpha (HSP90A)	TT78R5H	HS90A_HUMAN	Inhibitor	[2]
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SNX-2112 Interacts with 14 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Inhibitor of nuclear factor kappa-B kinase subunit alpha (CHUK)	OTLF4ZB1	IKKA_HUMAN	Decreases Expression	[4]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[4]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[4]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Decreases Expression	[4]
Endoplasmin (HSP90B1)	OT02XLBR	ENPL_HUMAN	Decreases Expression	[4]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Expression	[4]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[4]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Expression	[4]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[4]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Expression	[4]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[4]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[4]
Heat shock protein 75 kDa, mitochondrial (TRAP1)	OTNG0L8J	TRAP1_HUMAN	Decreases Expression	[4]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[4]
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⏷ Show the Full List of 14 DOT(s)

Indication(s) of 10-hydroxycamptothecin

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[3]

10-hydroxycamptothecin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase I (TOP1)	TTGTQHC	TOP1_HUMAN	Inhibitor	[3]
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10-hydroxycamptothecin Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[5]
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10-hydroxycamptothecin Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Response To Substance	[6]
E3 ubiquitin-protein ligase Mdm2 (MDM2)	OTOVXARF	MDM2_HUMAN	Affects Response To Substance	[7]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Response To Substance	[6]
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Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Ewing sarcoma-peripheral primitive neuroectodermal tumour	DC93ESL	ES2	Investigative	[8]
Carcinoma	DCBJ5ZR	OV90	Investigative	[1]
Carcinoma	DCEL6FF	EFM192B	Investigative	[1]
Carcinoma	DCFTFMH	MDAMB436	Investigative	[1]
Colon carcinoma	DC8B6X5	RKO	Investigative	[1]
Rectal adenocarcinoma	DCP11S1	SW837	Investigative	[1]
Adenocarcinoma	DC1IIBI	CAOV3	Investigative	[9]
Adenocarcinoma	DCANRJR	OVCAR3	Investigative	[9]
Adenocarcinoma	DCXP2JZ	A427	Investigative	[9]
Adenocarcinoma	DCD7R11	NCIH1650	Investigative	[9]
Adenocarcinoma	DC3Q9HX	NCIH2122	Investigative	[9]
Adenocarcinoma	DC9HM8I	DLD1	Investigative	[9]
Adenocarcinoma	DC4NSF8	HCT116	Investigative	[9]
Adenocarcinoma	DC7SB24	SW-620	Investigative	[9]
Amelanotic melanoma	DCO90PJ	A2058	Investigative	[9]
Germ cell tumour	DC3IBVQ	PA1	Investigative	[9]
Large cell lung carcinoma	DCMWXGG	NCI-H460	Investigative	[9]
Malignant melanoma	DC5OEZQ	A375	Investigative	[9]
Malignant melanoma	DCGHUWR	HT144	Investigative	[9]
Malignant melanoma	DCFUW4Z	RPMI7951	Investigative	[9]
Malignant melanoma	DC6EM8H	SKMEL30	Investigative	[9]
Malignant melanoma	DCIG8QC	UACC62	Investigative	[9]
Mesothelioma	DCED0WS	MSTO	Investigative	[9]
Non small cell carcinoma	DCR3QZ4	SKMES1	Investigative	[9]
Ovarian endometrioid adenocarcinoma	DCQCD32	A2780	Investigative	[9]
Ovarian serous cystadenocarcinoma	DCHMH0N	SK-OV-3	Investigative	[9]
Prostate carcinoma	DCSUVTN	LNCAP	Investigative	[9]
Prostate carcinoma	DC7X0HL	VCAP	Investigative	[9]
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⏷ Show the Full List of 28 DrugCom(s)

References

1	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.
2	Heat shock protein 90: inhibitors in clinical trials. J Med Chem. 2010 Jan 14;53(1):3-17.
3	Upregulation of p21WAF1/CIP1 in human breast cancer cell lines MCF-7 and MDA-MB-468 undergoing apoptosis induced by natural product anticancer drugs 10-hydroxycamptothecin and camptothecin through p53-dependent and independent pathways. Int J Oncol. 1998 Apr;12(4):793-804.
4	The Hsp90 inhibitor SNX-2112, induces apoptosis in multidrug resistant K562/ADR cells through suppression of Akt/NF-B and disruption of mitochondria-dependent pathways. Chem Biol Interact. 2013 Sep 5;205(1):1-10. doi: 10.1016/j.cbi.2013.06.007. Epub 2013 Jun 15.
5	Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
6	siRNA-mediated Bcl-2 and Bcl-xl gene silencing sensitizes human hepatoblastoma cells to chemotherapeutic drugs. Clin Exp Pharmacol Physiol. 2007 May-Jun;34(5-6):450-6. doi: 10.1111/j.1440-1681.2007.04593.x.
7	Antisense therapy targeting MDM2 oncogene in prostate cancer: Effects on proliferation, apoptosis, multiple gene expression, and chemotherapy. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11636-41. doi: 10.1073/pnas.1934692100. Epub 2003 Sep 16.
8	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.
9	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.