Details of the Drug

General Information of Drug (ID: DMVP4E5)

• Drug Name: AZD6482
• Synonyms: AZD6482; 1173900-33-8; AZD 6482; (R)-2-(1-(7-methyl-2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl)ethylamino)benzoic acid; 2-[[(1R)-1-[7-Methyl-2-(4-morpholinyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl]ethyl]amino]benzoic acid; AZD-6482; CHEMBL2165191; UNII-78G6MP5PZ5; 78G6MP5PZ5; 2-({(1R)-1-[7-Methyl-2-(morpholin-4-yl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl]ethyl}amino)benzoic acid; 2-{[(1R)-1-[7-methyl-2-(morpholin-4-yl)-4-oxopyrido[1,2-a]pyrimidin-9-yl]ethyl]amino}benzoic acid

Indication

Disease Entry	ICD 11	Status	REF
Thrombosis	DB61-GB90	Terminated	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 408.4
  Topological Polar Surface Area (xlogp); 2
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 7
• Chemical Identifiers:
  Formula: C22H24N4O4
  IUPAC Name: 2-[[(1R)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoic acid
  Canonical SMILES: CC1=CN2C(=O)C=C(N=C2C(=C1)[C@@H](C)NC3=CC=CC=C3C(=O)O)N4CCOCC4
  InChI: InChI=1S/C22H24N4O4/c1-14-11-17(15(2)23-18-6-4-3-5-16(18)22(28)29)21-24-19(12-20(27)26(21)13-14)25-7-9-30-10-8-25/h3-6,11-13,15,23H,7-10H2,1-2H3,(H,28,29)/t15-/m1/s1
  InChIKey: IRTDIKMSKMREGO-OAHLLOKOSA-N
• Cross-matching ID:
  PubChem CID: 44137675
  ChEBI ID: CHEBI:91359
  CAS Number: 1173900-33-8
  TTD ID: D0D0QA

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	Modulator	[2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Thrombosis
• ICD Disease Classification: DB61-GB90

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] 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: 8059).
• [2] 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.
• [3] Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
• [4] 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).
• [5] The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res. 2011 May 15;17(10):3272-81.
• [6] National Cancer Institute Drug Dictionary (drug id 751594).
• [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: 7967).
• [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] Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.
• [10] 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.
• [11] 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.
• [12] Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated immune tolerance to cancer. Nature. 2014 Jun 19;510(7505):407-11.