Details of the Drug Combination

General Information of Drug Combination (ID: DCT7HLP)

Drug Combination Name

SNX-2112 Ridaforolimus

Indication

Disease Entry	Status	REF
Prostate carcinoma	Investigative	[1]

Component Drugs

SNX-2112 DMB5A80

Ridaforolimus DMLHEU7

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: LNCAP

Zero Interaction Potency (ZIP) Score: 5.11

Bliss Independence Score: 0.39

Loewe Additivity Score: 0.06

LHighest Single Agent (HSA) Score: 4.03

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]
------------------------------------------------------------------------------------

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]
------------------------------------------------------------------------------------


⏷ Show the Full List of 14 DOT(s)

Indication(s) of Ridaforolimus

Disease Entry	ICD 11	Status	REF
Sarcoma	2A60-2C35	Phase 3	[3]

Ridaforolimus Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Inhibitor	[5]
------------------------------------------------------------------------------------

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Carcinoma	DCJCHWI	EFM192B	Investigative	[6]
Carcinoma	DC2WE6M	MDAMB436	Investigative	[6]
Colon carcinoma	DCS3TSH	RKO	Investigative	[6]
Invasive ductal carcinoma	DCVBB2F	T-47D	Investigative	[6]
Adenocarcinoma	DCX1QTU	CAOV3	Investigative	[1]
Adenocarcinoma	DCMTTD3	NCIH2122	Investigative	[1]
Adenocarcinoma	DCKXLSW	DLD1	Investigative	[1]
Adenocarcinoma	DCWM032	HCT116	Investigative	[1]
Adenocarcinoma	DCYPS1H	SW-620	Investigative	[1]
Amelanotic melanoma	DCH19O2	A2058	Investigative	[1]
Germ cell tumour	DCM8Y2J	PA1	Investigative	[1]
Large cell lung carcinoma	DCT6FGM	NCI-H460	Investigative	[1]
Malignant melanoma	DC1NNPI	A375	Investigative	[1]
Malignant melanoma	DCDSY16	HT144	Investigative	[1]
Non small cell carcinoma	DCXOV9U	SKMES1	Investigative	[1]
------------------------------------------------------------------------------------


⏷ Show the Full List of 15 DrugCom(s)

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	Heat shock protein 90: inhibitors in clinical trials. J Med Chem. 2010 Jan 14;53(1):3-17.
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: 7884).
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	A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
6	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.