Details of the Drug

General Information of Drug (ID: DM4XMF7)

• Drug Name: LY2606368
• Synonyms: prexasertib; Prexasertib; 1234015-52-1; UNII-820NH671E6; LY-2606368; 820NH671E6; Prexasertib [USAN]; 5-((5-(2-(3-aminopropoxy)-6-methoxyphenyl)-1H-pyrazol-3-yl)amino)pyrazine-2-carbonitrile; 5-({5-[2-(3-aminopropoxy)-6-methoxyphenyl]-1H-pyrazol-3-yl}amino)pyrazine-2-carbonitrile; 5-[[5-[2-(3-aminopropoxy)-6-methoxyphenyl]-1H-pyrazol-3-yl]amino]pyrazine-2-carbonitrile; SCHEMBL1975451; GTPL9549; SCHEMBL19457660; SCHEMBL18989301; CHEMBL3544911; EX-A758; DOTGPNHGTYJDEP-UHFFFAOYSA-N; AOB87325; ZINC95837013

Indication

Disease Entry	ICD 11	Status	REF
Ovarian cancer	2C73	Phase 2	[1]
Small-cell lung cancer	2C25.Y	Phase 2	[1]
Head and neck cancer	2D42	Phase 1	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]
Squamous cell anal carcinoma	2C00.3	Phase 1	[3]

• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 365.4
  Topological Polar Surface Area (xlogp); 1.4
  Rotatable Bond Count (rotbonds); 8
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 8
• Chemical Identifiers:
  Formula: C18H19N7O2
  IUPAC Name: 5-[[5-[2-(3-aminopropoxy)-6-methoxyphenyl]-1H-pyrazol-3-yl]amino]pyrazine-2-carbonitrile
  Canonical SMILES: COC1=C(C(=CC=C1)OCCCN)C2=CC(=NN2)NC3=NC=C(N=C3)C#N
  InChI: InChI=1S/C18H19N7O2/c1-26-14-4-2-5-15(27-7-3-6-19)18(14)13-8-16(25-24-13)23-17-11-21-12(9-20)10-22-17/h2,4-5,8,10-11H,3,6-7,19H2,1H3,(H2,22,23,24,25)
  InChIKey: DOTGPNHGTYJDEP-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 46700756
  CAS Number: 1234015-52-1
  DrugBank ID: DB12008
  TTD ID: D08UUL

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	[1], [3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Ovarian cancer
• ICD Disease Classification: 2C73

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] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Clinical pipeline report, company report or official report of Eli Lilly.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [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] 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.