GDC-0425

• CAT Number: I006939
• CAS Number: 1200129-48-1
• Molecular Formula: C18H19N5O
• Molecular Weight: 321.38
• Purity: ≥95%
• Synonyms: GDC0425; GDC-0425; GDC 0425; RG7602; RG-7602; RG 7602.;5-((1-ethylpiperidin-4-yl)oxy)-9H-pyrrolo[2,3-b:5,4-c/’]dipyridine-6-carbonitrile
• Target: Chk1 inhibitor.
• Solubility: Soluble in DMSO, not in water
• Storage: 0 - 4°C for short term or -20 °C for long term
• 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
• 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
• SMILES: CCN1CCC(CC1)OC2=C3C4=C(NC3=CN=C2C#N)N=CC=C4

GDC-0425 (Cat.No:I006939), also known as RG7602. is an oral, selective Chk1 inhibitor. GDC-0425 enhances gemcitabine (gem) efficacy in tumor xenograft models. Greater chemopotentiation is observed in cancer cell lines lacking p53 activity. GDC-0425 blocks the function of a protein called checkpoint kinase 1 (Chk1). GDC-0425 was safe and yielded responses in patients with a variety of cancer types, including triple-negative breast cancer, melanoma, and cancer of unknown primary, according to data from a phase I clinical trial presented at the AACR Annual Meeting 2015, held April 18-22.

Reference

1:Novel Mechanism of Decyanation of GDC-0425 by Cytochrome P450. Takahashi RH, Halladay JS, Siu M, Chen Y, Hop CE, Khojasteh SC, Ma S.Drug Metab Dispos. 2017 May;45(5):430-440. doi: 10.1124/dmd.116.074336. Epub 2017 Feb 10. PMID: 28188299 2:Phase I Study of GDC-0425, a Checkpoint Kinase 1 Inhibitor, in Combination with Gemcitabine in Patients with Refractory Solid Tumors. Infante JR, Hollebecque A, Postel-Vinay S, Bauer TM, Blackwood EM, Evangelista M, Mahrus S, Peale FV, Lu X, Sahasranaman S, Zhu R, Chen Y, Ding X, Murray ER, Schutzman JL, Lauchle JO, Soria JC, LoRusso PM.Clin Cancer Res. 2017 May 15;23(10):2423-2432. doi: 10.1158/1078-0432.CCR-16-1782. Epub 2016 Nov 4. PMID: 27815358 3:A supported liquid extraction LC-MS/MS method for determination of concentrations of GDC-0425, a small molecule Checkpoint kinase 1 inhibitor, in human plasma. Ding X, Chen Y, Sahasranaman S, Shi Y, McKnight J, Dean B.Biomed Chromatogr. 2016 Dec;30(12):1984-1991. doi: 10.1002/bmc.3775. Epub 2016 Jul 5. PMID: 27245274