IPI-549

Izina ryimiti:

(S) -2-amino-N- (1- (8 - ( ) ethyl) pyrazolo [1,5-a] pyrimidine-3-carboxamide

Kode ya 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.

InChi Code:

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 Urufunguzo:

XUMALORDVCFWKV-IBGZPJMESA-N

Ijambo ryibanze:

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

Gukemura:Gukemura muri DMSO

Ububiko:0 - 4 ° C mugihe gito (iminsi kugeza ibyumweru), cyangwa -20 ° C mugihe kirekire (amezi).

Ibisobanuro:

IPI-549 ibuza PI3Kγ hamwe na IC50 ya 16 nM, hamwe> guhitamo inshuro 100 kurenza izindi lipide na protein kinase (PI3Kα IC50 = 3.2 μM, PI3Kβ IC50 = 3.5 μM, PI3Kδ IC50> 8.4 μM). IPI549 isuzumwa kubikorwa murwego rwose I PI3K isoforms. Guhuza IPI549 kuri PI3K-γ bigenwa no gupima igipimo cyumuntu kugiti cye no kuri PI3K-α, β na δ ukoresheje titre de equilibrium fluorescent. IPI549 isanga ari ihuriro ridasanzwe kuri PI3Kγ hamwe na Kd ya 290 pM na> inshuro 58 zidakomeye kubandi bo mu cyiciro cya I PI3K isoforms (PI3Kα Kd = 17 nM, PI3Kβ Kd = 82 nM, PI3Kδ Kd = 23 M). Muri PI3K-α, -β, -γ, na -δ biterwa na selile fosifore-AKT ivuga, IPI549 yerekana imbaraga za PI3K-γ imbaraga (IC50 = 1.2 nM) hamwe no guhitamo kurwanya isoforms yo mu cyiciro cya I PI3K (> inshuro 146). Cellular IC50s yo mu cyiciro cya I PI3Kα (250 nM), PI3Kβ (240 nM), PI3Kγ (1.2 nM), PI3Kδ (180 nM) byagenwe muri selile SKOV-3, 786-O, RAW 264.7, na RAJI, ukurikije gukurikirana kubuza pAKT S473 na ELISA. Byongeye kandi, igipimo cya IPI549 kibuza PI3Kγ guterwa n'amagufwa ya macrophage (BMDM) kwimuka. IPI549 isanga kandi ihitamo kurwanya itsinda rya GPCR 80, imiyoboro ya ion, hamwe nabatwara kuri 10 μM [1].

Intego: PI3Kγ, PI3Kβ