Ipatasertib
(GDC-0068, RG7440)
- Phase
- I
- II
- III
- Phase
- I
- II
- III
- Phase
- I
- II
- III
- Phase
- I
- II
- III
- Phase
- I
- II
- III
- Phase
- I
- II
- III
- Phase
- I
- II
- III
- Phase
- I
- II
- III
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 inhibitor1
Ipatasertib is an investigational, orally administered, ATP-competitive, selective AKT inhibitor. AKT is a key component of the PI3K/AKT pathway. This pathway is dysregulated in many malignancies, often through acquisition of activating mutations in AKT and phosphatidylinositol 3-kinase (PI3K), loss of the tumor suppressor phosphatase and tensin homolog (PTEN), or amplification of AKT and PI3K.1
Some cancer treatments have led to the aberrant activation of the
PI3K/AKT pathway, which resulted in the survival and proliferation of
tumor cells.1-4 In various preclinical models,
PI3K/AKT/mammalian target of rapamycin (mTOR) signaling was shown to
become activated following chemotherapy or antihormonal therapy.3,4
Ipatasertib is designed to target and bind to the
adenosine triphosphate (ATP)-binding pocket of the 3 activated
isoforms of AKT, potentially inhibiting downstream
signaling.1 Ipatasertib is being investigated in
combination with various treatment modalities (eg, antihormonal
therapy, chemotherapy).1,4
1 Ipatasertib is an oral, investigational small molecule currently being studied for its potential to inhibit all 3 isoforms of AKT.1,5 Aberrant AKT signaling is associated with resistance to apoptosis and increased cell growth, proliferation, and metabolism.1-3
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.1,6
3 Preclinical data have shown that ipatasertib induced tumor growth delay or regression in AKT-activated tumor cells and xenograft models.1 Ipatasertib continues to be investigated in ongoing clinical studies.
FOXO=Forkhead box O; GSK3=glycogen synthase kinase
3; mTORC=mammalian target of rapamycin complex;
PDK1=phosphoinositide-dependent kinase-1;
PI4,5P2=phosphatidylinositol 4,5-bisphosphate;
PIP3=phosphatidylinositol 3,4,5-trisphosphate;
RTK=receptor tyrosine kinase.
References
- Lin J, Sampath D, Nannini MA, et al. Clin Cancer Res. 2013;19:1760-1772. PMID: 23287563
- Slomovitz BM, Coleman RL. Clin Cancer Res. 2012;18:5856-5864. PMID: 23082003
- Huang WC, Hung MC. J Formos Med Assoc. 2009;108:180-194. PMID: 19293033
- Beeram M, Tan QT, Tekmal RR, Russell D, Middleton A, DeGraffenried LA. Ann Oncol. 2007;18:1323-1328. PMID: 17693645
- Nitulescu GM, Margina D, Juzenas P, et al. Int J Oncol. 2016;48:869-885. PMID: 26698230
- Hung CM, Garcia-Haro L, Sparks CA, Guertin DA. Cold Spring Harb Perspect Biol. 2012;4:1-17. PMID: 23124837
