Ipatasertib

• CAT Number: I007346
• CAS Number: 1001264-89-6
• Molecular Formula: C24H32ClN5O2
• Molecular Weight: 458.00
• Purity: ≥95%
• Synonyms: (2S)-2-(4-chlorophenyl)-1-[4-[(5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]piperazin-1-yl]-3-(propan-2-ylamino)propan-1-one
• InChI: InChI=1S/C24H32ClN5O2/c1-15(2)26-13-19(17-4-6-18(25)7-5-17)24(32)30-10-8-29(9-11-30)23-21-16(3)12-20(31)22(21)27-14-28-23/h4-7,14-16,19-20,26,31H,8-13H2,1-3H3/t16-,19-,20-/m1/s1
• InChIKey: GRZXWCHAXNAUHY-NSISKUIASA-N
• SMILES: CC1CC(C2=C1C(=NC=N2)N3CCN(CC3)C(=O)C(CNC(C)C)C4=CC=C(C=C4)Cl)O

Ipatasertib (GDC-0068) is an orally active, highly selective and ATP-competitive pan-Akt inhibitor with IC50 values of 5, 18, 8 nM for Akt1/2/3, respectively. Ipatasertib synchronously activates FoxO3a and NF-κB through inhibition of Akt leading to p53-independent activation of PUMA. Ipatasertib also induces apoptosis in cancer cells and inhibits tumor growth in xenograft mouse models[1][2].
Ipatasertib (10 µM; 12, 24 h) suppresses colon cancer cell proliferation by p53 irrespectively activating PUMA in vitro[1].
Ipatasertib (1, 5, 10, 20 μM; 24 h/10 μM; 3, 6, 12, 24 h) up-regulates the expression level of PUMA in a concentration and time dependent manner in HCT116 cells[1].
Ipatasertib increases the mRNA level of PUMA in HCT116 WT, p53−/−, and DLD1 (p53 mutant) cells[1].
Ipatasertib (10 µM; 24 h) induces apoptosis through PUMA/Bax pathway in HCT116 cells[1].
Ipatasertib (30 mg/kg; p.o.; single daily for 15 consecutive days) exhibits PUMA-dependent antitumor activity in HCT116 WT and PUMA−/− cells xenograft nude mice model[1].

Reference

[1]. Sun L, et al. Ipatasertib, a novel Akt inhibitor, induces transcription factor FoxO3a and NF-κB directly regulates PUMA-dependent apoptosis. Cell Death Dis. 2018 Sep 5;9(9):911.
 [Content Brief]

[2]. Blake JF, et al. Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors. J Med Chem. 2012 Sep 27;55(18):8110-27.
 [Content Brief]