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Purity: ≥98%
Ipatasertib (formerly also called GDC-0068; RG-7440) is a novel, potent, orally bioavailable, ATP-competitive and highly selective pan-Akt inhibitor that targets Akt1/2/3 and may have anticancer activity. With IC50 values of 5 nM, 18 nM, or 8 nM in cell-free assays, it inhibits Akt1/2/3 with 620-fold selectivity for Akt1/2/3 over PKA. The drug GDC-0068 is used to treat human cancers. The PI3K-AKT pathway controls tumorigenesis, cell proliferation, and cell survival. GDC-0068 binds to and inhibits the activation of AKT, causing cell cycle arrest, reducing the growth of cancerous cells, and inducing tumor cell death. Because the PI3K-AKT pathway is frequently activated in tumors, GDC-0068 is highly sensitive to PTEN or PI3K mutations that result in AKT activation.
| Targets |
Akt1 (IC50 = 5 nM); Akt3 (IC50 = 8 nM); Akt2 (IC50 = 18 nM); PKA (IC50 = 3100 nM)
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|---|---|
| ln Vitro |
GDC-0068 only inhibits 3 kinases by >70% at 1 μM concentration when tested against a large panel of 230 kinases (PRKG1α, PRKG1β, and p70S6K, with IC50 values of 98 nM, 69 nM, and 860 nM, respectively). GDC-0068 has an IC50 of 3.1 μM and exhibits >100-fold selectivity for Akt over PKA. With IC50 values of 157 nM, 197 nM, and 208 nM, respectively, GDC-0068 treatment inhibits the phosphorylation of the Akt substrate, PRAS40, in LNCaP, PC3, and BT474M1 cells. Additionally, the Akt-signaling-driven cancer cell lines that have defects in the tumor suppressor PTEN, oncogenic mutations in PIK3CA, and HER2 amplification are all selectively inhibited by GDC-0068, with the strongest effects seen in the HER2+ and Luminal subtypes. [1-4]
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| ln Vivo |
GDC-0068 oral administration causes the down-regulation of p-PRAS40 in PC3 prostate tumor xenograft models. GDC-0068 treatment in BT474-Tr xenografts lowers pS6 and peIF4G levels, relocalizes FOXO3a to the nucleus, and causes feedback upregulation of HER3 and pERK. In numerous xenograft tumor models, including the PTEN-deficient prostate cancer models LNCaP and PC3, the PIK3CA H1047R mutant breast cancer model KPL-4, and the MCF7-neo/HER2 tumor model, administration of GDC-0068 demonstrates potent antitumor efficacy.[1-4]
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| Animal Protocol |
Female nude mice bearing LNCaP, PC3, KPL-4, or MCF7 tumor xenografts
~100 mg/kg/day Orally |
| References |
| Molecular Formula |
C24H32CLN5O2
|
|---|---|
| Molecular Weight |
457.9962
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| Exact Mass |
457.22445
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| Elemental Analysis |
C, 62.94; H, 7.04; Cl, 7.74; N, 15.29; O, 6.99
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| CAS # |
1001264-89-6
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| Related CAS # |
Ipatasertib dihydrochloride;1396257-94-5
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| Appearance |
Solid powder
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| SMILES |
C[C@@H]1C[C@H](C2=C1C(=NC=N2)N3CCN(CC3)C(=O)[C@H](CNC(C)C)C4=CC=C(C=C4)Cl)O
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| InChi Key |
GRZXWCHAXNAUHY-NSISKUIASA-N
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| InChi Code |
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
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| Chemical Name |
(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
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| Synonyms |
GDC0068; GDC 0068; GDC-0068; RG-7440; RG 7440; RG7440; Ipatasertib
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~92 mg/mL (~200.9 mM)
Water: <1 mg/mL Ethanol: ~92 mg/mL (~200.9 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 5% DMSO+40% PEG 300+5%Tween80+ 50%ddH2O: 92mg/ml Solubility in Formulation 5: 10 mg/mL (21.83 mM) in 0.5% MC 0.5% Tween-80 (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1834 mL | 10.9170 mL | 21.8341 mL | |
| 5 mM | 0.4367 mL | 2.1834 mL | 4.3668 mL | |
| 10 mM | 0.2183 mL | 1.0917 mL | 2.1834 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04464174 | Active Recruiting |
Drug: Ipatasertib | Triple Negative Breast Cancer | MedSIR | October 8, 2020 | Phase 2 |
| NCT03072238 | Active Recruiting |
Drug: Ipatasertib Drug: Placebo |
Metastatic Prostate Cancer | Hoffmann-La Roche | June 30, 2017 | Phase 3 |
| NCT03395899 | Active Recruiting |
Drug: Ipatasertib Drug: Bevacizumab P |
Breast Cancer Estrogen Receptor-positive Breast Cancer |
Queen Mary University of London | December 21, 2017 | Phase 2 |
| NCT03853707 | Active Recruiting |
Drug: Ipatasertib Drug: Paclitaxel |
Anatomic Stage IV Breast Cancer AJCC v8 Metastatic Triple-Negative Breast Carcinoma |
City of Hope Medical Center | March 4, 2019 | Phase 1 Phase 3 |
| NCT04060862 | Active Recruiting |
Drug: Ipatasertib Drug: Placebo |
Breast Cancer | Hoffmann-La Roche | November 15, 2019 | Phase 3 |
Dose-dependent effect of GDC-0068 on Akt pathway biomarkers. Clin Canc Res 2013, 19:1760–1772. |
Single agent efficacy of GDC-0068 in human tumor xenograft models. |
Pharmacokinetic (PK) and pharmacodynamic (PD) relationship of GDC-0068 in xenograft models. |
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