Details of the Drug Combination

General Information of Drug Combination (ID: DCHMSDZ)

Drug Combination Name

PHA848125 BMS-754807

Indication

Disease Entry	Status	REF
Diffuse intrinsic pontine glioma	Investigative	[1]

Component Drugs

PHA848125 DMS2Q9G

BMS-754807 DMPK32V

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: DIPG25

Zero Interaction Potency (ZIP) Score: 5.614

Bliss Independence Score: 5.215

Loewe Additivity Score: 9.633

LHighest Single Agent (HSA) Score: 12.197

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of PHA848125

Disease Entry	ICD 11	Status	REF
Thymic cancer	2C27	Phase 2	[2]

PHA848125 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Cyclin-dependent kinase 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[3]
------------------------------------------------------------------------------------

BMS-754807 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
RAC-alpha serine/threonine-protein kinase (AKT1)	TTWTSCV	AKT1_HUMAN	Inhibitor	[4]
------------------------------------------------------------------------------------

BMS-754807 Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[5]
Insulin-like growth factor 1 receptor (IGF1R)	OTXJIF13	IGF1R_HUMAN	Decreases Phosphorylation	[5]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Decreases Phosphorylation	[5]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Increases Response To Substance	[5]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Decreases Response To Substance	[5]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Response To Substance	[5]
------------------------------------------------------------------------------------


⏷ Show the Full List of 6 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: 7938).
3	Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. J Med Chem. 2009 Aug 27;52(16):5152-63.
4	Discovery of a 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitor (BMS-754807) of insulin-like growth factor receptor (IGF-1R) kinase in cli... J Med Chem. 2009 Dec 10;52(23):7360-3.
5	CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers. Cancer Res. 2014 Jul 15;74(14):3947-58. doi: 10.1158/0008-5472.CAN-13-2923. Epub 2014 Jul 1.