| Identification | Back Directory | [Name]
PKI-179 | [CAS]
1197160-28-3 | [Synonyms]
PKI-179
PKI179,PKI 179
1-(4-(4-(3-Oxa-8-azabicyclo[3.2.1]octan-8-yl)-6-morpholino-1,3,5-triazin-2-yl)phenyl)-3-(pyrid
1-(4-(4-(3-Oxa-8-azabicyclo[3.2.1]octan-8-yl)-6-morpholino-1,3,5-triazin-2-yl)phenyl)-3-(pyridin-4-yl)urea
Urea, N-[4-[4-(4-morpholinyl)-6-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1,3,5-triazin-2-yl]phenyl]-N'-4-pyridinyl- | [Molecular Formula]
C25H28N8O3 | [MDL Number]
MFCD28400129 | [MOL File]
1197160-28-3.mol | [Molecular Weight]
488.54 |
| Chemical Properties | Back Directory | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: 50mg/mL | [form ]
Solid | [color ]
Off-white to yellow | [InChIKey]
WXUUCRLKXQMWRY-UHFFFAOYSA-N | [SMILES]
O=C(NC1=CC=NC=C1)NC2=CC=C(C=C2)C3=NC(N4[C@H]5COC[C@@H]4CC5)=NC(N6CCOCC6)=N3.[xH2O] |
| Hazard Information | Back Directory | [Uses]
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]. | [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.
|
| [IC 50]
mTOR: 0.42 nM (IC50); PI3Kα: 8 nM (IC50); PI3Kβ: 24 nM (IC50); PI3Kγ: 74 nM (IC50); PI3Kδ: 77 nM (IC50); E545K: 14 nM (IC50); H1047R: 11 nM (IC50) | [References]
[1] Venkatesan AM, et, al. PKI-179: an orally efficacious dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor. Bioorg Med Chem Lett. 2010 Oct 1;20(19):5869-73. DOI:10.1016/j.bmcl.2010.07.104
[2] Rehan M. A structural insight into the inhibitory mechanism of an orally active PI3K/mTOR dual inhibitor, PKI-179 using computational approaches. J Mol Graph Model. 2015 Nov;62:226-234. DOI:10.1016/j.jmgm.2015.10.005 |
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Merck KGaA
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21-20338288 |
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www.sigmaaldrich.cn |
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CHEMSWORTH
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+91-261-2397244 |
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www.chemsworth.com |
| Company Name: |
Matrix Scientific
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803 788-9494 All other calls |
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www.matrixscientific.com |
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