Details of the Drug Combination

General Information of Drug Combination (ID: DC60NVT)

Drug Combination Name

SCH 727965 Ridaforolimus

Indication

Disease Entry	Status	REF
Amelanotic melanoma	Investigative	[1]

Component Drugs

SCH 727965 DMCJLD1

Ridaforolimus DMLHEU7

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: A2058

Zero Interaction Potency (ZIP) Score: 9.78

Bliss Independence Score: 10.55

Loewe Additivity Score: 4.12

LHighest Single Agent (HSA) Score: 13.7

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 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	[7]
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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	DC0BICP	ES2	Investigative	[8]
Breast and ovarian cancer syndrome	DCQ2OYW	UWB1289	Investigative	[9]
Breast and ovarian cancer syndrome	DC72FKC	UWB1289+BRCA1	Investigative	[9]
Breast carcinoma	DCNDLIW	KPL1	Investigative	[9]
Breast carcinoma	DCGKR47	OCUBM	Investigative	[9]
Carcinoma	DCXC8ZA	EFM192B	Investigative	[9]
Carcinoma	DCFEANK	MDAMB436	Investigative	[9]
Colon adenocarcinoma	DCH9K1D	LOVO	Investigative	[9]
Colon carcinoma	DC14K0D	RKO	Investigative	[9]
Rectal adenocarcinoma	DCGD6X4	SW837	Investigative	[9]
Adenocarcinoma	DCDEMPY	CAOV3	Investigative	[1]
Adenocarcinoma	DCMTW0E	A427	Investigative	[1]
Adenocarcinoma	DCIKHF6	NCIH1650	Investigative	[1]
Adenocarcinoma	DCMK9Y9	NCIH23	Investigative	[1]
Adenocarcinoma	DCP8IOP	NCIH520	Investigative	[1]
Adenocarcinoma	DCYFQOS	COLO320DM	Investigative	[1]
Adenocarcinoma	DC9K291	HT29	Investigative	[1]
Adenocarcinoma	DCZTKNF	SW-620	Investigative	[1]
Adenocarcinoma	DCHJI10	HCT116	Investigative	[1]
Germ cell tumour	DCCFMW0	PA1	Investigative	[1]
Large cell lung carcinoma	DCAPBAE	NCI-H460	Investigative	[1]
Malignant melanoma	DCRS76M	A375	Investigative	[1]
Malignant melanoma	DC916VH	RPMI7951	Investigative	[1]
Malignant melanoma	DCXCA3V	UACC62	Investigative	[1]
Mesothelioma	DC6WQ7G	MSTO	Investigative	[1]
Ovarian endometrioid adenocarcinoma	DC0RRZX	A2780	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCJMWA6	SK-OV-3	Investigative	[1]
Prostate carcinoma	DCPXSYD	LNCAP	Investigative	[1]
Prostate carcinoma	DC3DXJR	VCAP	Investigative	[1]
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⏷ Show the Full List of 29 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	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	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	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.
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.