This compound and its uses are investigational and have not been approved by the US Food and Drug Administration. Efficacy and safety have not been established. The information presented should not be construed as a recommendation for use. The relevance of findings in preclinical studies to humans is currently being evaluated.
Ipatasertib, an Akt inhibitor
Ipatasertib is an orally administered, ATP-competitive, small-molecule inhibitor of Akt. Akt is a key component of the PI3K/Akt/mTOR pathway, and is dysregulated in a number of malignancies through loss of the tumor suppressor PTEN, acquisition of activating mutations, or amplification of PI3K.1
In various preclinical models, PI3K/Akt/mTOR signaling has been shown to become activated following chemotherapy or antihormonal therapy. These alterations led to the aberrant activation of the Akt signaling cascade, resulting in the survival and proliferation of tumor cells. Ipatasertib is designed to target and bind to the ATP-binding pocket of the 3 isoforms of Akt, potentially inhibiting downstream signaling. Ipatasertib is being investigated in combination with various treatment modalities (eg, antihormonal therapy, chemotherapy).1-4
1 Ipatasertib (GDC-0068, RG7440) is an oral investigational small molecule currently being studied for its potential to inhibit all 3 isoforms of Akt.5
2 Ipatasertib is designed to bind to the ATP-binding pocket of the 3 isoforms of Akt. By inhibiting Akt serine-threonine kinase activity, ipatasertib may inhibit tumor growth and proliferation through mTOR, as well as activate apoptotic signaling through FOXO.1,6
3 Preclinical data have shown that ipatasertib induced tumor growth delay or regression in Akt-activated tumor cell xenograft models.1 Ipatasertib continues to be investigated in ongoing clinical studies.
PI3K=phosphatidylinositol 3-kinase; mTOR=mammalian target of rapamycin.
- Lin J, Sampath D, Nannini MA, et al. Targeting activated Akt with GDC-0068, a novel selective Akt inhibitor that is efficacious in multiple tumor models. Clin Cancer Res. 2013;19:1760-1772. PMID: 23287563
- Huang WC, Hung MC. Induction of Akt activity by chemotherapy confers acquired resistance. J Formos Med Assoc. 2009;108:180-194. PMID: 19293033
- Beeram M, Tan QT, Tekmal RR, Russell D, Middleton A, DeGraffenried LA. Akt-induced endocrine therapy resistance is reversed by inhibition of mTOR signaling. Ann Oncol. 2007;18:1323-1328. PMID: 17693645
- Slomovitz BM, Coleman RL. The PI3K/AKT/mTOR pathway as a therapeutic target in endometrial cancer. Clin Cancer Res. 2012;18:5856-5864. PMID: 23082003
- Nitulescu GM, Margina D, Juzenas P, et al. Akt inhibitors in cancer treatment: the long journey from drug discovery to clinical use (review). Int J Oncol. 2016;48:869-885. PMID: 26698230
- Hung CM, Garcia-Haro L, Sparks CA, Guertin DA. mTOR-dependent cell survival mechanisms. Cold Spring Harb Perspect Biol. 2012;4:1-17. PMID: 23124837