Details of the Drug

General Information of Drug (ID: DM1FW0C)

• Drug Name: AZD7762
• Synonyms: AZD7762; 860352-01-8; AZD-7762; (S)-5-(3-Fluorophenyl)-N-(piperidin-3-yl)-3-ureidothiophene-2-carboxamide; AZD 7762; UNII-5D822Y3L1H; 3-(Carbamoylamino)-5-(3-Fluorophenyl)-N-[(3s)-Piperidin-3-Yl]thiophene-2-Carboxamide; CHEMBL2041933; 5D822Y3L1H; J-502468; 5-(3-Fluorophenyl)-N-[(3s)-3-Piperidyl]-3-Ureido-Thiophene-2-Carboxamide; IAYGCINLNONXHY-LBPRGKRZSA-N; YDJ; AZD7762 hydrochloride; 5-(3-Fluorophenyl)-3-ureidothiophene-N-[(S)-piperidin-3-yl]-2-carboxamide; SCHEMBL1127614; GTPL7713; AOB1915; QCR-261; CHEBI:131156

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 362.4
  Topological Polar Surface Area (xlogp); 2.3
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C17H19FN4O2S
  IUPAC Name: 3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-2-carboxamide
  Canonical SMILES: C1C[C@@H](CNC1)NC(=O)C2=C(C=C(S2)C3=CC(=CC=C3)F)NC(=O)N
  InChI: InChI=1S/C17H19FN4O2S/c18-11-4-1-3-10(7-11)14-8-13(22-17(19)24)15(25-14)16(23)21-12-5-2-6-20-9-12/h1,3-4,7-8,12,20H,2,5-6,9H2,(H,21,23)(H3,19,22,24)/t12-/m0/s1
  InChIKey: IAYGCINLNONXHY-LBPRGKRZSA-N
• Cross-matching ID:
  PubChem CID: 11152667
  ChEBI ID: CHEBI:131156
  CAS Number: 860352-01-8
  DrugBank ID: DB12242
  TTD ID: D0PM7Q

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Checkpoint kinase-1 (CHK1)	TTTU902	CHK1_HUMAN	Inhibitor	[3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Solid tumour/cancer
• ICD Disease Classification: 2A00-2F9Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Checkpoint kinase-1 (CHK1)	DTT	CHEK1	7.22E-191	1.43	4.74

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: 7713).
• [2] ClinicalTrials.gov (NCT00473616) Phase I Single Ascending Dose/Multiple Ascending Dose in Patients Treated With AZD7762 and Irinotecan. U.S. National Institutes of Health.
• [3] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [4] Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs. 2014 Apr;32(2):213-26.
• [5] Characterization of an inhibitory dynamic pharmacophore for the ERCC1-XPA interaction using a combined molecular dynamics and virtual screening app... J Mol Graph Model. 2009 Sep;28(2):113-30.
• [6] Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening. Mol Cancer Ther. 2011 Apr;10(4):591-602.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] A phase Ib study of oral Chk1 inhibitor LY2880070 in combination with gemcitabine in patients with advanced or metastatic cancer. Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 3581-3581.
• [9] National Cancer Institute Drug Dictionary (drug id 730054).
• [10] Quantitative assessment of BCL-2:BIM complexes as a pharmacodynamic marker for venetoclax (ABT-199).
• [11] Chk1 Inhibitor MK-8776 Restores the Sensitivity of Chemotherapeutics in P-glycoprotein Overexpressing Cancer Cells. Int J Mol Sci. 2019 Aug 22;20(17):4095.
• [12] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [13] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.