Details of the Drug

General Information of Drug (ID: DMDZ26X)

Drug Name

GDC-0425

Indication

Disease Entry	ICD 11	Status	REF
Lymphoma	2A80-2A86	Phase 1	[1]

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

321.4

Topological Polar Surface Area (xlogp)

2.6

Rotatable Bond Count (rotbonds)

3

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

5

Chemical Identifiers

Formula: C18H19N5O
IUPAC Name: 3-(1-ethylpiperidin-4-yl)oxy-5,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaene-4-carbonitrile
Canonical SMILES: CCN1CCC(CC1)OC2=C3C4=C(NC3=CN=C2C#N)N=CC=C4
InChI: InChI=1S/C18H19N5O/c1-2-23-8-5-12(6-9-23)24-17-14(10-19)21-11-15-16(17)13-4-3-7-20-18(13)22-15/h3-4,7,11-12H,2,5-6,8-9H2,1H3,(H,20,22)
InChIKey: XEZLBMHDUXSICI-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 58266779
CAS Number: 1627539-18-7
DrugBank ID: DB14791
TTD ID: D01ZUV

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	Modulator	[2]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Lymphoma

ICD Disease Classification

2A80-2A86

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

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	ClinicalTrials.gov (NCT01359696) A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0425 Administered With and Without Gemcitabine in Patients With Refractory Solid Tumors or Lymphoma. U.S. National Institutes of Health.
2	Quantitative assessment of BCL-2:BIM complexes as a pharmacodynamic marker for venetoclax (ABT-199).
3	Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs. 2014 Apr;32(2):213-26.
4	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.
5	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.
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	Clinical pipeline report, company report or official report of AstraZeneca (2009).
10	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.
11	Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
12	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.