Details of the Drug

General Information of Drug (ID: DMCBGLW)

• Drug Name: GSK2636771
• Synonyms: GSK2636771; 1372540-25-4; GSK-2636771; 2-methyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-morpholino-1H-benzo[d]imidazole-4-carboxylic acid; UNII-DW94IAT0LS; DW94IAT0LS; GSK 2636771; 2-Methyl-1-((2-methyl-3-(trifluoromethyl)phenyl)methyl)-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylic acid; 2-methyl-1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-morpholin-4-ylbenzimidazole-4-carboxylic acid; lic acid; XTKLTGBKIDQGQL-UHFFFAOYSA-N

Indication

Disease Entry	ICD 11	Status	REF
Prostate cancer	2C82.0	Phase 1	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[2], [3]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 433.4
  Topological Polar Surface Area (xlogp); 4
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 8
• Chemical Identifiers:
  Formula: C22H22F3N3O3
  IUPAC Name: 2-methyl-1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-morpholin-4-ylbenzimidazole-4-carboxylic acid
  Canonical SMILES: CC1=C(C=CC=C1C(F)(F)F)CN2C(=NC3=C(C=C(C=C32)N4CCOCC4)C(=O)O)C
  InChI: InChI=1S/C22H22F3N3O3/c1-13-15(4-3-5-18(13)22(23,24)25)12-28-14(2)26-20-17(21(29)30)10-16(11-19(20)28)27-6-8-31-9-7-27/h3-5,10-11H,6-9,12H2,1-2H3,(H,29,30)
  InChIKey: XTKLTGBKIDQGQL-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 56949517
  CAS Number: 1372540-25-4
  DrugBank ID: DB11795
  TTD ID: D0G3MN

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
PI3-kinase beta (PIK3CB)	TTTHBCA	PK3CB_HUMAN	Inhibitor	[2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Prostate cancer
• ICD Disease Classification: 2C82.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
PI3-kinase beta (PIK3CB)	DTT	PIK3CB	8.82E-15	0.24	0.54

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [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: 7967).
• [3] ClinicalTrials.gov (NCT01458067) A Phase I/IIa, First Time in Human, Study of GSK2636771 in Subjects With Advanced Solid Tumors With Phosphatase and Tensin Homolog (PTEN) Deficiency. U.S. National Institutes of Health.
• [4] Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
• [5] 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. (Target id: 2154).
• [6] The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res. 2011 May 15;17(10):3272-81.
• [7] National Cancer Institute Drug Dictionary (drug id 751594).
• [8] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [9] Human target validation of phosphoinositide 3-kinase (PI3K)beta: effects on platelets and insulin sensitivity, using AZD6482 a novel PI3Kbeta inhibitor. J Thromb Haemost. 2012 Oct;10(10):2127-36.
• [10] Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.
• [11] Synthesis and biological evaluation of sulfonylhydrazone-substituted imidazo[1,2-a]pyridines as novel PI3 kinase p110alpha inhibitors. Bioorg Med Chem. 2007 Sep 1;15(17):5837-44.
• [12] 1-substituted (Dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-ones endowed with dual DNA-PK/PI3-K inhibitory activity. J Med Chem. 2013 Aug 22;56(16):6386-401.
• [13] Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated immune tolerance to cancer. Nature. 2014 Jun 19;510(7505):407-11.