Saukewa: IP-549

Sunan Sinadari:

(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

Lambar SMILES:

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

Lambar InChi:

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

Mabuɗin kalma:

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

Solubility:Mai narkewa a cikin DMSO

Ajiya:0 - 4°C na gajeren lokaci (kwanaki zuwa makonni), ko -20°C na dogon lokaci (watanni).

Bayani:

IPI-549 yana hana PI3Kγ tare da IC50 na 16 nM, tare da> 100-fold selectivity akan sauran lipid da protein kinases (PI3Kα IC50 = 3.2 μM, PI3Kβ IC50 = 3.5 μM, PI3Kδ IC50> 8.4 μM). An kimanta IPI549 don ayyuka a cikin duk isoforms na Class I PI3K. Ƙunƙarar ɗaurin IPI549 don PI3K-γ an ƙaddara ta hanyar auna ƙimar ƙimar kowane mutum kuma don PI3K-α, β da δ ta amfani da ma'auni mai kyalli. An samo IPI549 a matsayin mai ɗaure mai ban mamaki ga PI3Kγ tare da Kd na 290 pM da> 58-ninki mai rauni mai rauni don sauran isoforms na Class I PI3K (PI3Kα Kd = 17 nM, PI3Kβ Kd = 82 nM, PI3Kδ Kd=23 M). A cikin PI3K-α, -β, -γ, da -δ masu dogara da salon salula phospho-AKT gwaje-gwaje, IPI549 yana nuna kyakkyawan ƙarfin PI3K-γ (IC50 = 1.2 nM) da zaɓi a kan sauran Class I PI3K isoforms (> 146-ninka). IC50s na salula don Class I PI3KA (250 nM), PI3Kβ (240 nM), PI3Kγ (1.2 nM), PI3Kγ (180 nM) an ƙaddara su a cikin SKOV-3, 786-O, RAW 264.7, da RAJI Kwayoyin, bi da bi, ta hanyar saka idanu. hana pAKT S473 ta ELISA. Bugu da ƙari, kashi IPI549 dogara yana hana PI3Kγ dogara ga kasusuwan kasusuwan macrophage (BMDM) ƙaura. Hakanan ana samun IPI549 a matsayin zaɓi akan rukunin GPCRs 80, tashoshi ion, da masu jigilar kaya a 10 μM[1].

manufa: PI3Kγ, PI3Kβ