Details of the Drug Combination

General Information of Drug Combination (ID: DCMJ4VA)

Drug Combination Name

Pelitinib SCH 727965

Indication

Disease Entry	Status	REF
Ewing sarcoma	Investigative	[1]

Component Drugs

Pelitinib DMIW453

SCH 727965 DMCJLD1

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: TC-71

Zero Interaction Potency (ZIP) Score: 5.277

Bliss Independence Score: 3.79

Loewe Additivity Score: 0.524

LHighest Single Agent (HSA) Score: 3.677

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Pelitinib

Disease Entry	ICD 11	Status	REF
Lymphoma	2A80-2A86	Phase 2	[2]

Pelitinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Modulator	[4]
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Pelitinib Interacts with 14 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB)	OT9RDS3H	IKKB_HUMAN	Decreases Expression	[5]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[5]
B-cell lymphoma/leukemia 10 (BCL10)	OT47MCLI	BCL10_HUMAN	Decreases Expression	[5]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Activity	[6]
Transcription factor Sp1 (SP1)	OTISPT4X	SP1_HUMAN	Decreases Activity	[5]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[5]
Cyclic AMP-dependent transcription factor ATF-1 (ATF1)	OT251CI0	ATF1_HUMAN	Decreases Expression	[5]
B-cell lymphoma 3 protein (BCL3)	OT1M5B95	BCL3_HUMAN	Decreases Expression	[5]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Expression	[5]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Expression	[5]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[5]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[5]
Baculoviral IAP repeat-containing protein 1 (NAIP)	OTLA925F	BIRC1_HUMAN	Decreases Expression	[5]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Expression	[5]
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⏷ Show the Full List of 14 DOT(s)

Indication(s) of SCH 727965

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

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	[7]
Cyclin-dependent kinase 1 (CDK1)	TTH6V3D	CDK1_HUMAN	Inhibitor	[7]
Cyclin-dependent kinase 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[7]
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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	[8]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[8]
Breast cancer type 1 susceptibility protein (BRCA1)	OT5BN6VH	BRCA1_HUMAN	Decreases Expression	[9]
Breast cancer type 2 susceptibility protein (BRCA2)	OTF1XSV1	BRCA2_HUMAN	Decreases Expression	[9]
DNA repair protein RAD51 homolog 1 (RAD51)	OTNVWGC1	RAD51_HUMAN	Decreases Expression	[9]
Fanconi anemia group D2 protein (FANCD2)	OTVEB5LF	FACD2_HUMAN	Decreases Expression	[9]
Cyclin-dependent kinase 12 (CDK12)	OTZUDGNU	CDK12_HUMAN	Decreases Activity	[9]
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⏷ Show the Full List of 7 DOT(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: 7644).
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: 7379).
4	EGFR tyrosine kinase inhibitor pelitinib regulates radiation-induced p65-dependent telomerase activation in squamous cell carcinoma.Radiat Res.2013 Mar;179(3):304-12.
5	Irreversible EGFR inhibitor EKB-569 targets low-LET -radiation-triggered rel orchestration and potentiates cell death in squamous cell carcinoma. PLoS One. 2011;6(12):e29705. doi: 10.1371/journal.pone.0029705. Epub 2011 Dec 29.
6	Cysteine mapping in conformationally distinct kinase nucleotide binding sites: application to the design of selective covalent inhibitors. J Med Chem. 2011 Mar 10;54(5):1347-55. doi: 10.1021/jm101396q. Epub 2011 Feb 15.
7	Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
8	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.
9	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.