GDC-0068 --- Akt Inhibitor

GDC-0068 is a highly potent, selective, and orally available pan-Akt inhibitor, targeting Akt1, Akt2 and Akt3 with IC50 of 5 nM, 18 nM and 8 nM, respectively. It has >100-fold selectivity over a broad panel of 230 kinases, except PRKG1α and PRKG1β with IC50 of 98 nM and 69 nM. GDC-0068 can effectively block Akt signaling and induce cell cycle arrest in human cancer cell lines in vitro, and exhibit significant efficacy in PTEN- and PI3K mutant xenograft models, including PTEN-deficient prostate cancer models LNCaP and PC3, the PIK3CA H1047R mutant breast cancer model KPL-4, and MCF7-neo/HER2 tumor model. A Phase I study of GDC-0068 in patients with refractory solid tumors is ongoing.

Product information

CAS Number: 1001264-89-6

Molecular Weight: 458.00

Formula: C24H32ClN5O2

Synonym:

Ipatasertib

Chemical Name: (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)propan-1-one

Smiles: CC(C)NC[C@H](C1=CC=C(Cl)C=C1)C(=O)N1CCN(CC1)C1=NC=NC2[C@H](O)C[C@@H](C)C=21

InChiKey: GRZXWCHAXNAUHY-NSISKUIASA-N

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

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 100 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

GDC-0068 was used at 5-10 µM final concentration in vitro and in cellular assays.

In Vivo:

GDC-0068 was orally dosed to mice at 50-100 mg/kg once per day, or in combination with MEK inhibitors or chemotherapy agents to significantly reduce the tumor volume. Formulation: 0.5% methylcellulose/0.2% Tween-80.

References:

1. Blake JF, et al. Discovery and Preclinical Pharmacology of a Selective ATP-Competitive Akt Inhibitor (GDC-0068) for the Treatment of Human Tumors. (2012) J Med Chem. 55(18):8110-27.
2. Heidi M, et al. Abstract 966: Predictive biomarkers of the AKT inhibitor, GDC-0068, in single agent and combination studies. (2012) Cancer Research. Volume 72, Issue 8, Supplement 1
3. Kui Lin. Abstract DDT02-01: GDC-0068: A novel, selective, ATP-competitive inhibitor of Akt. (2011) Cancer Research. Volume 71, Issue 8, Supplement 1

Products are for research use only. Not for human use.

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