Details of the Drug

General Information of Drug (ID: DMIN0SV)

• Drug Name: GSK2269557

Indication

Disease Entry	ICD 11	Status	REF
Asthma	CA23	Phase 2	[1]

• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 440.5
  Topological Polar Surface Area (xlogp); 3.9
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C26H28N6O
  IUPAC Name: 2-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-5-[(4-propan-2-ylpiperazin-1-yl)methyl]-1,3-oxazole
  Canonical SMILES: CC(C)N1CCN(CC1)CC2=CN=C(O2)C3=C4C=NNC4=CC(=C3)C5=C6C=CNC6=CC=C5
  InChI: InChI=1S/C26H28N6O/c1-17(2)32-10-8-31(9-11-32)16-19-14-28-26(33-19)22-12-18(13-25-23(22)15-29-30-25)20-4-3-5-24-21(20)6-7-27-24/h3-7,12-15,17,27H,8-11,16H2,1-2H3,(H,29,30)
  InChIKey: MCIDWGZGWVSZMK-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 49784002
  CAS Number: 1254036-71-9
  TTD ID: D06GUA

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Stress-activated protein kinase (p38)	TTWELHI	NOUNIPROTAC	Inhibitor	[2]

References

• [1] ClinicalTrials.gov (NCT02522299) A Study to Evaluate the Safety, Efficacy and Changes in Induced Sputum and Blood Biomarkers Following Daily Repeat Doses of Inhaled GSK2269557 in Chronic Obstructive Pulmonary Disease (COPD) Subjects With Acute Exacerbation.
• [2] Evaluation of WO2012032067 and WO2012055846: two selective PI3Kdelta inhibitors, which is GSK-2269557. Expert Opin Ther Pat. 2012 Aug;22(8):965-70.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Synthesis and evaluation of carbamoylmethylene linked prodrugs of BMS-582949, a clinical p38alpha inhibitor. Bioorg Med Chem Lett. 2013 May 15;23(10):3028-33.
• [5] Investigational p38 inhibitors for the treatment of chronic obstructive pulmonary disease. Expert Opin Investig Drugs. 2015 Mar;24(3):383-92.
• [6] Inhibition of Wnt/beta-catenin signaling by p38 MAP kinase inhibitors is explained by cross-reactivity with casein kinase Idelta/ . Chem Biol. 2011 Apr 22;18(4):485-94.
• [7] 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: 7959).
• [8] Cmpany report (Arraybiopharma)
• [9] US patent application no. 2008,0269,123, Methods for treating polycystic kidney disease (pkd) or other cyst forming diseases.
• [10] The discovery of N-cyclopropyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzamide (AZD6703), a clinical p38alpha MAP kinase inhibitor for the treatment of inflammatory diseases. Bioorg Med Chem Lett. 2012 Jun 15;22(12):3879-83.
• [11] US patent application no. 2008,0119,498, Therapeutic agent for pruritus comprising p38 map kinase inhibitor as the active ingredient.
• [12] p38 MAPK inhibitors ameliorate target organ damage in hypertension: Part 1. p38 MAPK-dependent endothelial dysfunction and hypertension. J Pharmacol Exp Ther. 2003 Dec;307(3):932-8.