GDC-0032

• CAT Number: I001112
• CAS Number: 1282512-48-4
• Molecular Formula: C₂₄H₂₈N₈O₂
• Molecular Weight: 460.53
• Purity: ≥95%
• Synonyms: GDC-0032
• Target: PI3K
• Solubility: 10 mM in DMSO
• Storage: 3 years -20C powder
• IC50: 0.29 nM/0.12 nM /0.97 nM(PI3Kα/δ/γ) [1]
• InChI: InChI=1S/C24H28N8O2/c1-14(2)32-22(27-15(3)29-32)19-13-30-8-9-34-20-10-16(6-7-18(20)21(30)28-19)17-11-26-31(12-17)24(4,5)23(25)33/h6-7,10-14H,8-9H2,1-5H3,(H2,25,33)
• InChIKey: BEUQXVWXFDOSAQ-UHFFFAOYSA-N
• SMILES: CC1=NN(C(=N1)C2=CN3CCOC4=C(C3=N2)C=CC(=C4)C5=CN(N=C5)C(C)(C)C(=O)N)C(C)C

Taselisib(cas 1282512-48-4), also known as GDC-0032, is a potent, next-generation β isoform-sparing PI3K inhibitor targeting PI3Kα/δ/γ with IC50 of 0.29 nM/0.12 nM/0.97nM, >10 fold selective over PI3Kβ.

Taselisib is an orally bioavailable, potent, and selective inhibitor of Class I PI3Kα, δ, and γ isoforms, with 30 fold less inhibition of the PI3K β isoform relative to the PI3Kα isoform. Preclinical data show that GDC-0032 has increased activity against PI3Kα isoform (PIK3CA) mutant and HER2-amplified cancer cell lines. GDC-0032 inhibits MCF7-neo/HER2 cells proliferation with IC50 of 2.5 nM. GDC-0032 pharmacokinetics is approximately dose proportional and time independent with a mean t1/2 of 40 hours. The combination of GDC-0032 enhances activity of fulvestrant resulting in tumor regressions and tumor growth delay (91% tumor growth inhibition (TGI)). In addition, the combination of GDC-0032 with tamoxifen enhances the efficacy of tamoxifen in vivo (102%TGI for GDC-0032).

Reference

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