Details of the Drug Combination

General Information of Drug Combination (ID: DCV8855)

Drug Combination Name

SCH 727965 SNX-2112

Indication

Disease Entry	Status	REF
Ewing sarcoma-peripheral primitive neuroectodermal tumour	Investigative	[1]

Component Drugs

SCH 727965 DMCJLD1

SNX-2112 DMB5A80

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: ES2

Zero Interaction Potency (ZIP) Score: 5.69

Bliss Independence Score: 6.77

Loewe Additivity Score: 2.75

LHighest Single Agent (HSA) Score: 9.48

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of SCH 727965

Disease Entry	ICD 11	Status	REF
Acute lymphoblastic leukaemia	2A85	Discontinued in Phase 3	[2]

SCH 727965 Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Cyclin-dependent kinase 9 (CDK9)	TT1LVF2	CDK9_HUMAN	Inhibitor	[4]
Cyclin-dependent kinase 1 (CDK1)	TTH6V3D	CDK1_HUMAN	Inhibitor	[4]
Cyclin-dependent kinase 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[4]
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SCH 727965 Interacts with 7 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Phosphorylation	[5]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[5]
Breast cancer type 1 susceptibility protein (BRCA1)	OT5BN6VH	BRCA1_HUMAN	Decreases Expression	[6]
Breast cancer type 2 susceptibility protein (BRCA2)	OTF1XSV1	BRCA2_HUMAN	Decreases Expression	[6]
DNA repair protein RAD51 homolog 1 (RAD51)	OTNVWGC1	RAD51_HUMAN	Decreases Expression	[6]
Fanconi anemia group D2 protein (FANCD2)	OTVEB5LF	FACD2_HUMAN	Decreases Expression	[6]
Cyclin-dependent kinase 12 (CDK12)	OTZUDGNU	CDK12_HUMAN	Decreases Activity	[6]
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⏷ Show the Full List of 7 DOT(s)

Indication(s) of SNX-2112

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

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	[3]
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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	[7]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[7]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[7]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Decreases Expression	[7]
Endoplasmin (HSP90B1)	OT02XLBR	ENPL_HUMAN	Decreases Expression	[7]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Expression	[7]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[7]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Expression	[7]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[7]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Expression	[7]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[7]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[7]
Heat shock protein 75 kDa, mitochondrial (TRAP1)	OTNG0L8J	TRAP1_HUMAN	Decreases Expression	[7]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[7]
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⏷ Show the Full List of 14 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast and ovarian cancer syndrome	DCVMJQ6	UWB1289	Investigative	[8]
Breast carcinoma	DCBAY93	OCUBM	Investigative	[8]
Carcinoma	DCMBCYK	EFM192B	Investigative	[8]
Carcinoma	DCFZ852	MDAMB436	Investigative	[8]
Colon adenocarcinoma	DCUJXOJ	LOVO	Investigative	[8]
Colon carcinoma	DC3VM0G	RKO	Investigative	[8]
Invasive ductal carcinoma	DC5UA49	T-47D	Investigative	[8]
Rectal adenocarcinoma	DCSP8J2	SW837	Investigative	[8]
Adenocarcinoma	DCVZK22	CAOV3	Investigative	[9]
Adenocarcinoma	DCEJ0I0	OVCAR3	Investigative	[9]
Adenocarcinoma	DC6B7J1	A427	Investigative	[9]
Adenocarcinoma	DC99D59	NCIH1650	Investigative	[9]
Adenocarcinoma	DC6EYWZ	NCIH520	Investigative	[9]
Adenocarcinoma	DC3BZZM	COLO320DM	Investigative	[9]
Adenocarcinoma	DCJCPPS	DLD1	Investigative	[9]
Adenocarcinoma	DCJDRIR	HCT116	Investigative	[9]
Adenocarcinoma	DC1P9RZ	HT29	Investigative	[9]
Adenocarcinoma	DCSK9RL	SW-620	Investigative	[9]
Amelanotic melanoma	DCX63AB	A2058	Investigative	[9]
Germ cell tumour	DCKIF96	PA1	Investigative	[9]
Large cell lung carcinoma	DCM4DWY	NCI-H460	Investigative	[9]
Malignant melanoma	DCMLM2Y	A375	Investigative	[9]
Malignant melanoma	DCRUBB6	HT144	Investigative	[9]
Malignant melanoma	DCDX2E6	RPMI7951	Investigative	[9]
Malignant melanoma	DCJW0L0	SKMEL30	Investigative	[9]
Malignant melanoma	DCW9K9E	UACC62	Investigative	[9]
Mesothelioma	DCFCGM5	MSTO	Investigative	[9]
Non small cell carcinoma	DCUB2MT	SKMES1	Investigative	[9]
Ovarian endometrioid adenocarcinoma	DCOFKPH	A2780	Investigative	[9]
Ovarian serous cystadenocarcinoma	DCUZS0S	SK-OV-3	Investigative	[9]
Prostate carcinoma	DC0L9XJ	LNCAP	Investigative	[9]
Prostate carcinoma	DC9EN77	VCAP	Investigative	[9]
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⏷ Show the Full List of 32 DrugCom(s)

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	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: 7379).
3	Heat shock protein 90: inhibitors in clinical trials. J Med Chem. 2010 Jan 14;53(1):3-17.
4	Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
5	Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor. Mol Cancer Ther. 2010 Aug;9(8):2344-53. doi: 10.1158/1535-7163.MCT-10-0324. Epub 2010 Jul 27.
6	CDK12 Inhibition Reverses De Novo and Acquired PARP Inhibitor Resistance in BRCA Wild-Type and Mutated Models of Triple-Negative Breast Cancer. Cell Rep. 2016 Nov 22;17(9):2367-2381. doi: 10.1016/j.celrep.2016.10.077.
7	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.
8	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.
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.