Details of the Drug Combination

General Information of Drug Combination (ID: DC6EYWZ)

Drug Combination Name

SCH 727965 SNX-2112

Indication

Disease Entry	Status	REF
Adenocarcinoma	Investigative	[1]

Component Drugs

SCH 727965 DMCJLD1

SNX-2112 DMB5A80

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: NCIH520

Zero Interaction Potency (ZIP) Score: 7.86

Bliss Independence Score: 6.77

Loewe Additivity Score: 4.51

LHighest Single Agent (HSA) Score: 11.45

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

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


⏷ 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]
------------------------------------------------------------------------------------

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


⏷ 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
Ewing sarcoma-peripheral primitive neuroectodermal tumour	DCV8855	ES2	Investigative	[8]
Breast and ovarian cancer syndrome	DCVMJQ6	UWB1289	Investigative	[9]
Breast carcinoma	DCBAY93	OCUBM	Investigative	[9]
Carcinoma	DCMBCYK	EFM192B	Investigative	[9]
Carcinoma	DCFZ852	MDAMB436	Investigative	[9]
Colon adenocarcinoma	DCUJXOJ	LOVO	Investigative	[9]
Colon carcinoma	DC3VM0G	RKO	Investigative	[9]
Invasive ductal carcinoma	DC5UA49	T-47D	Investigative	[9]
Rectal adenocarcinoma	DCSP8J2	SW837	Investigative	[9]
Adenocarcinoma	DCVZK22	CAOV3	Investigative	[1]
Adenocarcinoma	DCEJ0I0	OVCAR3	Investigative	[1]
Adenocarcinoma	DC6B7J1	A427	Investigative	[1]
Adenocarcinoma	DC99D59	NCIH1650	Investigative	[1]
Adenocarcinoma	DC3BZZM	COLO320DM	Investigative	[1]
Adenocarcinoma	DCJCPPS	DLD1	Investigative	[1]
Adenocarcinoma	DCJDRIR	HCT116	Investigative	[1]
Adenocarcinoma	DC1P9RZ	HT29	Investigative	[1]
Adenocarcinoma	DCSK9RL	SW-620	Investigative	[1]
Amelanotic melanoma	DCX63AB	A2058	Investigative	[1]
Germ cell tumour	DCKIF96	PA1	Investigative	[1]
Large cell lung carcinoma	DCM4DWY	NCI-H460	Investigative	[1]
Malignant melanoma	DCMLM2Y	A375	Investigative	[1]
Malignant melanoma	DCRUBB6	HT144	Investigative	[1]
Malignant melanoma	DCDX2E6	RPMI7951	Investigative	[1]
Malignant melanoma	DCJW0L0	SKMEL30	Investigative	[1]
Malignant melanoma	DCW9K9E	UACC62	Investigative	[1]
Mesothelioma	DCFCGM5	MSTO	Investigative	[1]
Non small cell carcinoma	DCUB2MT	SKMES1	Investigative	[1]
Ovarian endometrioid adenocarcinoma	DCOFKPH	A2780	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCUZS0S	SK-OV-3	Investigative	[1]
Prostate carcinoma	DC0L9XJ	LNCAP	Investigative	[1]
Prostate carcinoma	DC9EN77	VCAP	Investigative	[1]
------------------------------------------------------------------------------------


⏷ Show the Full List of 32 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	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	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	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.