IPI-549

Non Chimik:

(S)-2-amino-N-(1-(8-((1-methyl-1H-pyrazol-4-yl)ethynyl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl )etil) pirazolo [1,5-a] pirimidin-3-karboksamid

Kòd 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

Kòd 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 kle:

XUMALORDVCFWKV-IBGZPJMESA-N

Mot:

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

Solibilite:Soluble nan DMSO

Depo:0 - 4 ° C pou kout tèm (jou a semèn), oswa -20 ° C pou tèm long (mwa).

Deskripsyon:

IPI-549 inibit PI3Kγ ak IC50 nan 16 nM, ak> 100-pliye selektivite sou lòt lipid ak pwoteyin kinaz (PI3Kα IC50 = 3.2 μM, PI3Kβ IC50 = 3.5 μM, PI3Kδ IC50> 8.4 μM). Yo evalye IPI549 pou aktivite atravè tout izofòm klas I PI3K. Afinite obligatwa IPI549 pou PI3K-γ detèmine lè w mezire konstan pousantaj endividyèl yo ak pou PI3K-α, β ak δ lè l sèvi avèk titration fliyoresan ekilib. IPI549 jwenn yon lyan konsiderableman sere nan PI3Kγ ak yon Kd nan 290 pM ak> 58 fwa pi fèb afinite pou lòt klas I PI3K izoform (PI3Kα Kd = 17 nM, PI3Kβ Kd = 82 nM, PI3Kδ Kd = 23 M). Nan PI3K-α, -β, -γ, ak -δ depandan selilè fosfo-AKT tès, IPI549 demontre ekselan pisans PI3K-γ (IC50 = 1.2 nM) ak selektivite kont lòt klas I PI3K izoform (> 146-pliye). IC50s selilè pou Klas I PI3Kα (250 nM), PI3Kβ (240 nM), PI3Kγ (1.2 nM), PI3Kδ (180 nM) yo detèmine nan SKOV-3, 786-O, RAW 264.7, ak selil RAJI, respektivman, pa siveyans. anpèchman pAKT S473 pa ELISA. Anplis de sa, dòz IPI549 depandan inibit PI3Kγ depandan migrasyon makwofaj mwèl zo (BMDM). IPI549 yo jwenn tou selektif kont yon panèl 80 GPCRs, chanèl ion, ak transpòtè nan 10 μM [1].

Sib: PI3Kγ, PI3Kβ