Ipatasertib (GDC-0068)

Catalog No.S2808 Batch:S280805

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Technical Data

Formula

C24H32ClN5O2
Molecular Weight 458 CAS No. 1001264-89-6
Solubility (25°C)* In vitro DMSO 91 mg/mL (198.68 mM)
Ethanol 91 mg/mL (198.68 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Ipatasertib (GDC-0068, RG7440) is a highly selective pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 5 nM/18 nM/8 nM in cell-free assays, 620-fold selectivity over PKA. Phase 2.
Targets
Akt1 [1]
(Cell-free assay)		 Akt3 [1]
(Cell-free assay)		 Akt2 [1]
(Cell-free assay)
5 nM 8 nM 18 nM
In vitro

Testing against a broad panel of 230 kinases, GDC-0068 only inhibits 3 kinases by >70% at 1 μM concentration (PRKG1α, PRKG1β, and p70S6K, with IC50 of 98 nM, 69 nM, and 860 nM, respectively). GDC-0068 displays >100-fold selectivity for Akt over PKA with IC50 of 3.1 μM. In LNCaP, PC3 and BT474M1 cells, GDC-0068 treatment inhibits the phosphorylation of the Akt substrate, PRAS40 with IC50 of 157 nM, 197 nM, and 208 nM, respectively. Furthermore, GDC-0068 selectively inhibits cell cycle progression and viability of cancer cell lines driven by Akt signaling, including those with defects in the tumor suppressor PTEN, oncogenic mutations in PIK3CA, and amplification of HER2, with strongest effects in HER2+ and Luminal subtypes. [1-4]
In vivo

Oral administration of GDC-0068 in PC3 prostate tumor xenografts model induces down-regulation of p-PRAS40. In BT474-Tr xenografts, GDC-0068 treatment reduces pS6 and peIF4G levels, re-localizes FOXO3a to nucleus, and induces feedback upregulation of HER3 and pERK. Administration of GDC-0068 exhibits potent antitumor efficacy in multiple xenograft tumor models, including the PTEN-deficient prostate cancer models LNCaP and PC3, the PIK3CA H1047R mutant breast cancer model KPL-4, and MCF7-neo/HER2 tumor model. [1-4]

Protocol (from reference)

Animal Study:

[1]
  • Animal Models

    Female nude mice bearing LNCaP, PC3, KPL-4, or MCF7 tumor xenografts

  • Dosages

    ~100 mg/kg/day

  • Administration

    Orally

Customer Product Validation

Data from [Data independently produced by , , Cell, 2015, 160(1-2): 161-76 ]

Data from [Data independently produced by , , Clin Cancer Res, 2018, 78(7):1657-1671]

Data from [Data independently produced by , , Neoplasia, 2017, 19(4):310-320]

Selleck's Ipatasertib (GDC-0068) has been cited by 127 publications

AKT and EZH2 inhibitors kill TNBCs by hijacking mechanisms of involution [ Nature, 2024, 10.1038/s41586-024-08031-6] PubMed: 39385030
Arachidonic acid released by PIK3CA mutant tumor cells triggers malignant transformation of colonic epithelium by inducing chromatin remodeling [ Cell Rep Med, 2024, S2666-3791(24)00179-4] PubMed: 38614093
Combined inhibition of CDK4/6 and AKT is highly effective against the luminal androgen receptor (LAR) subtype of triple negative breast cancer [ Cancer Lett, 2024, 604:217219] PubMed: 39244005
Assessments of prostate cancer cell functions highlight differences between a pan-PI3K/mTOR inhibitor, gedatolisib, and single-node inhibitors of the PI3K/AKT/mTOR pathway [ Mol Oncol, 2024, 10.1002/1878-0261.13703] PubMed: 39092562
The highly selective and oral phosphoinositide 3-kinase delta (PI3K-δ) inhibitor roginolisib induces apoptosis in mesothelioma cells and increases immune effector cell composition [ Transl Oncol, 2024, 43:101857] PubMed: 38412661
IFN-γ decreases PD-1 in T lymphocytes from convalescent COVID-19 patients via the AKT/GSK3β signaling pathway [ Sci Rep, 2024, 14(1):5038] PubMed: 38424104
Down-regulation of AKT proteins slows the growth of mutant-KRAS pancreatic tumors [ bioRxiv, 2024, 2024.05.03.592345] PubMed: 38746217
Cholesterol biosynthesis inhibition synergizes with AKT inhibitors in triple-negative breast cancer [ bioRxiv, 2024, 10.1101/2024.01.16.575899] PubMed: none
Proteomic Assessment of SKBR3/HER2+ Breast Cancer Cellular Response to Lapatinib and Investigational Ipatasertib Kinase Inhibitors [ bioRxiv, 2024, 2024.04.02.587656] PubMed: 38617302
Down-regulation of AKT proteins slows the growth of mutant-KRAS pancreatic tumors [ bioRxiv, 2024, 2024.05.03.592345] PubMed: 38746217

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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