Details of the Drug

General Information of Drug (ID: DM67EMK)

• Drug Name: SCH-900776
• Synonyms: CHEMBL1643208; MK-8776; 6-bromo-3-(1-methyl-1H-pyrazol-4-yl)-5-(piperidin-3-yl)pyrazolo[1,5-a]pyrimidin-7-amine; GTPL7943; SCHEMBL10380123; CHEBI:131165; HMS3656J19; BCP02883; BDBM50334854; AKOS026750519; MK 8776; NCGC00387868-02; DA-40779; 4CA-1150; BCP0726000317; J3.517.083I; 891494-63-6 pound not SCH900776 pound not SCH-900776; 6-bromo-3-(1-methylpyrazol-4-yl)-5-piperidin-3-ylpyrazolo[5,1-b]pyrimidin-7-amine; 6-bromo-3-(1-methylpyrazol-4-yl)-5-[(3S)-piperidin-3-yl]pyrazolo[1,5-a]pyrimidin-7-amine

Indication

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

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 376.25
  Topological Polar Surface Area (xlogp); 0.8
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C15H18BrN7
  IUPAC Name: 6-bromo-3-(1-methylpyrazol-4-yl)-5-[(3R)-piperidin-3-yl]pyrazolo[1,5-a]pyrimidin-7-amine
  Canonical SMILES: CN1C=C(C=N1)C2=C3N=C(C(=C(N3N=C2)N)Br)[C@@H]4CCCNC4
  InChI: InChI=1S/C15H18BrN7/c1-22-8-10(6-19-22)11-7-20-23-14(17)12(16)13(21-15(11)23)9-3-2-4-18-5-9/h6-9,18H,2-5,17H2,1H3/t9-/m1/s1
  InChIKey: GMIZZEXBPRLVIV-SECBINFHSA-N
• Cross-matching ID:
  PubChem CID: 46239015
  CAS Number: 891494-63-6
  DrugBank ID: DB11899
  TTD ID: D05FWH

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: 7943).
• [2] ClinicalTrials.gov (NCT01870596) Cytarabine With or Without SCH 900776 in Treating Adult Patients With Relapsed Acute Myeloid Leukemia. U.S. National Institutes of Health.
• [3] 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.
• [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] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] 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.
• [8] National Cancer Institute Drug Dictionary (drug id 730054).
• [9] Quantitative assessment of BCL-2:BIM complexes as a pharmacodynamic marker for venetoclax (ABT-199).
• [10] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [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.