1227911-45-6
1227911-45-6 structure
- Name: GSK2334470
- Chemical Name: (3S,6R)-1-[6-(3-amino-1H-indazol-6-yl)-2-(methylamino)pyrimidin-4-yl]-N-cyclohexyl-6-methylpiperidine-3-carboxamide
- CAS Number: 1227911-45-6
- Molecular Formula: C25H34N8O
- Molecular Weight: 462.591
- Catalog: Biochemical Inhibitor PI3K/Akt/mTOR inhibitor (PI3K/Akt/mTOR) PDK-1 inhibitor
- Create Date: 2017-03-08 23:44:37
- Modify Date: 2025-08-21 11:43:37
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GSK2334470 is a highly specific and potent inhibitor of PDK1 with an IC50 of 10 nM.
| Name | (3S,6R)-1-[6-(3-amino-1H-indazol-6-yl)-2-(methylamino)pyrimidin-4-yl]-N-cyclohexyl-6-methylpiperidine-3-carboxamide |
|---|---|
| Synonyms |
(3S,6R)-1-[6-(3-Amino-1H-indazol-6-yl)-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide
CS-0917 3-Piperidinecarboxamide, 1-[6-(3-amino-1H-indazol-6-yl)-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-, (3S,6R)- QC-8425 GSK2334470 |
| Description | GSK2334470 is a highly specific and potent inhibitor of PDK1 with an IC50 of 10 nM. |
|---|---|
| Related Catalog | |
| Target |
IC50: 10 nM(PDK1)[1] |
| In Vitro | Small molecule GSK2334470 inhibits PDK1 with an IC50 of ~10 nM, but does not suppress the activity of 93 other protein kinases including 13 AGC-kinases most related to PDK1 at 500-fold higher concentrations. Addition of GSK2334470 ablates T-loop residue phosphorylation and activation of SGK isoforms and S6K1 induced by serum or IGF-1 (insulin-like growth factor 1). GSK2334470 and AZD8055 effectively inhibite phosphorylation of PDK1 and mTOR, respectively, and induce higher G0–G1 ratio in LAN-1-MK than that in LAN-1 as well. PDK1 and mTOR inhibitors effecte on phosphorylation of GSK3β in some of resistant sublines[2]. |
| In Vivo | The efficacy of the PDK1 inhibitor (PDKi) GSK2334470 is tested in newborn BrafV600E::Pten−/−mice subjected to systemic administration of 4-HT. Twice weekly administration of PDK1 results in marked inhibition of pigmented lesions and concomitant melanomagenesis, as well as significant inhibition of lung metastases, seen by H&E staining-based quantification (~80%), and lymph node metastases as by S100 immunostaining, similar to the phenotype seen upon genetic ablation of Pdk1[3]. |
| Cell Assay | GSK2334470 is dissolved in DMSO and diluted with appropriate medium before use. To study the inhibitory effect of GSK2334470 on mTOR-S6K pathway, non-resistant cells and the resistant sublines are treated with GSK2334470 at 5 μM for 1.5 and 12 h in 10 % FBS medium with/without MK-2206 (5 μM)[2]. |
| Animal Admin | Mice is dissolved in DMSO and then diluted with PBS or saline. BrafV600E::Pten−/− are generated as previously described. Cohorts of six animals per group are used in each experimental group. GSK2334470 is administered through IP injection (100 mg/kg) 3 times per week starting the same day of topical administration of 4-hydroxytamoxifen and ending at the time of mouse collection, based on earlier studies[3]. |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Molecular Formula | C25H34N8O |
| Molecular Weight | 462.591 |
| Exact Mass | 462.285553 |
| PSA | 132.30000 |
| LogP | 2.31 |
| Appearance | white to light brown |
| Index of Refraction | 1.667 |
| Storage condition | 2-8°C |
| Water Solubility | DMSO: ≥10mg/mL |
| RIDADR | NONH for all modes of transport |
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1227911-45-6 |
| Literature: WO2010/59658 A1, ; Page/Page column 196 ; WO 2010/059658 A1 |
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1227911-45-6 |
| Literature: Journal of Medicinal Chemistry, , vol. 54, # 6 p. 1871 - 1895 |
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1227911-45-6 |
| Literature: Journal of Medicinal Chemistry, , vol. 54, # 6 p. 1871 - 1895 |
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1227911-45-6 |
| Literature: Journal of Medicinal Chemistry, , vol. 54, # 6 p. 1871 - 1895 |
| Precursor 4 | |
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| DownStream 0 | |