IPI-549

Dzina la Chemical:

(S) -2-amino-N-(1-(8-((1-methyl-1H-pyrazol-4-yl)ethynyl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl )ethyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

SMILES Kodi:

O=C(C1=C2N=CC=CN2N=C1N)N[C@H](C3=CC4=C(C(N3C5=CC=CC=C5)=O)C(C#CC6=CN(C) N=C6)=CC=C4)C

InChi kodi:

InChI=1S/C30H24N8O2/c1-19(34-29(39)26-27(31)35-37-15-7-14-32-28(26)37)24-16-22-9-6- 8-21(13-12-20-17 -33-36(2)18-20)25(22)30(40)38(24)23-10-4-3-5-11-23/h3-11,14-19H,1-2H3,( H2,31,35)(H,34,39)/t19-/m0/s1

InChi Key:

XUMALORDVCFWKV-IBGZPJMESA-N

Mawu ofunika:

IPI-549, IPI 549, IPI549, 1693758-51-8

Kusungunuka:Zosungunuka mu DMSO

Posungira:0 - 4 ° C kwa nthawi yochepa (masiku mpaka masabata), kapena -20 ° C kwa nthawi yaitali (miyezi).

Kufotokozera:

IPI-549 imalepheretsa PI3Kγ ndi IC50 ya 16 nM, ndi> 100-fold selectivity pa lipid kinase ndi mapuloteni ena (PI3Kα IC50 = 3.2 μM, PI3Kβ IC50 = 3.5 μM, PI3Kδ IC50> 8.4 μM). IPI549 imawunikidwa pa zochitika pamagulu onse a Class I PI3K isoforms. Kugwirizana kwa IPI549 kwa PI3K-γ kumatsimikiziridwa poyesa milingo yamunthu payekha komanso PI3K-α, β ndi δ pogwiritsa ntchito equilibrium fluorescent titration. IPI549 imapezeka kuti ndiyomangirira mochititsa chidwi ku PI3Kγ yokhala ndi Kd ya 290 pM ndi > 58-fold yofooka kuyanjana kwa ma isoform ena a Class I PI3K (PI3Kα Kd=17 nM, PI3Kβ Kd=82 nM, PI3Kδ Kd=23 M). Mu PI3K-α, -β, -γ, ndi -δ zoyeserera za phospho-AKT zodalira ma cell, IPI549 ikuwonetsa potency yabwino kwambiri ya PI3K-γ (IC50=1.2 nM) ndikusankha motsutsana ndi ma isoform ena a Class I PI3K (> 146-fold). Ma Cellular IC50s a Class I PI3Kα (250 nM), PI3Kβ (240 nM), PI3Kγ (1.2 nM), PI3Kδ (180 nM) amatsimikiziridwa mu SKOV-3, 786-O, RAW 264.7, ndi RAJI motsatira ma cell, motsatana. kuletsa kwa pAKT S473 ndi ELISA. Kuphatikiza apo, mlingo wa IPI549 modalira umalepheretsa PI3Kγ kusamuka kwa fupa la macrophage (BMDM). IPI549 imapezekanso kuti ndi yosankha motsutsana ndi gulu la 80 GPCRs, ma ion channels, ndi transporters pa 10 μM[1].

Zolinga: PI3Kγ,PI3Kβ