Antibodies
GDC-0068
- 貨號 Cat. No.
- S2808
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
GDC-0068
Catalog No.S2808
GDC-0068 is a highly selective pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 5 nM/18 nM/8 nM, 620-fold selectivity over PKA. Phase 2.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | GDC-0068 is a highly selective pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 5 nM/18 nM/8 nM, 620-fold selectivity over PKA. Phase 2. | |||||
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| Targets | Akt1 | Akt2 | Akt3 | |||
| IC50 | 5 nM | 18 nM | 8 nM [1] | |||
| 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] | |||||
| Features | ||||||
Protocol(Only for 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 |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01090960 | Active, not recruiting | Solid Cancers | Genentech | 2010-03 | Phase 1 |
| NCT01362374 | Recruiting | Solid Cancers | Genentech | 2011-07 | Phase 1 |
| NCT01485861 | Active, not recruiting | Prostate Cancer | Genentech | 2011-12 | Phase 2 |
| NCT01562275 | Recruiting | Neoplasms | Genentech | 2012-04 | Phase 1 |
Chemical Information
| Molecular Weight (MW) | 458 |
|---|---|
| Formula | C24H32ClN5O2 |
| CAS No. | 1001264-89-6 |
| Storage | 3 years -20℃Powder |
|---|---|
| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 92 mg/mL (200 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | 92 mg/mL (200 mM) | ||
| * <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. | |||
| 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 |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
|---|---|---|---|---|
| Mass(mg) | 0.458 | 4.58 | 9.16 | 13.74 |
