1197160-28-3
1197160-28-3 structure
- Name: PKI-179
- Chemical Name: 1-[4-[4-morpholin-4-yl-6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1,3,5-triazin-2-yl]phenyl]-3-pyridin-4-ylurea
- CAS Number: 1197160-28-3
- Molecular Formula: C25H28N8O3
- Molecular Weight: 488.54200
- Catalog: Signaling Pathways PI3K/Akt/mTOR mTOR
- Create Date: 2016-06-08 14:24:01
- Modify Date: 2024-01-08 21:38:53
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PKI-179 is a potent and orally active dual PI3K/mTOR inhibitor, with IC50s of 8 nM, 24 nM, 74 nM, 77 nM, and 0.42 nM for PI3K-α, PI3K-β, PI3K-γ, PI3K-δ and mTOR, respectively. PKI-179 also exhibits activity over E545K and H1047R, with IC50s of 14 nM and 11 nM, respectively. PKI-179 shows anti-tumor activity in vivo[1][2].
| Name | 1-[4-[4-morpholin-4-yl-6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1,3,5-triazin-2-yl]phenyl]-3-pyridin-4-ylurea |
|---|---|
| Synonyms | pki-179 |
| Description | PKI-179 is a potent and orally active dual PI3K/mTOR inhibitor, with IC50s of 8 nM, 24 nM, 74 nM, 77 nM, and 0.42 nM for PI3K-α, PI3K-β, PI3K-γ, PI3K-δ and mTOR, respectively. PKI-179 also exhibits activity over E545K and H1047R, with IC50s of 14 nM and 11 nM, respectively. PKI-179 shows anti-tumor activity in vivo[1][2]. |
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| Related Catalog | |
| Target |
PI3Kα:8 nM (IC50) PI3Kβ:24 nM (IC50) PI3Kγ:74 nM (IC50) PI3Kδ:77 nM (IC50) mTOR:0.42 nM (IC50) E545K:14 nM (IC50) H1047R:11 nM (IC50) |
| In Vitro | PKI-179 inhibits the cell proliferation, with IC50s of 22 nM and 29 nM for MDA361 and PC3 cells, respectively[1]. PKI-179 shows inhibitory activity against a panel of 361 other kinases, hERG and cytochrome P450 (CYP) isoforms at concentrations up to >30 μM, but does have activity for CYP2C8 (IC50=3 μM)[1]. |
| In Vivo | PKI-179 (5-50 mg/kg; p.o. once daily for 40 days) inhibits the tumor growth and is well tolerated in nude mice bearing MDA-361 human breast cancer tumors[1]. PKI-179 (50 mg/kg; p.o.) results in good inhibition of PI3K signaling in nude mice bearing MDA361 tumor xenografts[1]. PKI-179 exhibits good oral bioavailability (98% in nude mouse, 46% in rat, 38% in monkey, and 61% in dog) and a high half-life (>60 min) [1]. Animal Model: Nude mice bearing MDA-361 human breast cancer tumors[1] Dosage: 5, 10, 25, 50 mg/kg Administration: I.p. every 3 days for 4 weeks Result: Exhibited pronounced tumor growth arrest when dosed above 10 mg/kg. No significant weight loss of tested animals was observed for all different dosages. |
| References |
| Molecular Formula | C25H28N8O3 |
|---|---|
| Molecular Weight | 488.54200 |
| Exact Mass | 488.22800 |
| PSA | 120.86000 |
| LogP | 2.40670 |