IPI-549

Igama leMchiza:

(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

Ikhowudi yoncumo:

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

Ikhowudi ye-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

Isitshixo se-InChi:

XUMALORDVCFWKV-IBGZPJMESA-N

Igama elingundoqo:

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

Ukunyibilika:Inyibilika kwi-DMSO

Ugcino:0 - 4°C ixesha elifutshane (iintsuku ukuya kwiiveki), okanye -20°C ixesha elide (iinyanga).

Inkcazo:

I-IPI-549 inqanda i-PI3Kγ kunye ne-IC50 ye-16 nM, kunye > i-100-fold selectivity phezu kwezinye i-lipid kunye neprotein kinases (PI3Kα IC50 = 3.2 μM, PI3Kβ IC50 = 3.5 μM, PI3Kδ IC50>8.4 μM). IPI549 ivavanyelwa umsebenzi kuyo yonke iClass I PI3K isoforms. Unxulumano olubophelelayo lwe-IPI549 lwe-PI3K-γ lumiselwa ngokulinganisa iireyithi zomntu ngamnye kunye ne-PI3K-α, β kunye ne-δ kusetyenziswa i-equilibrium fluorescent titration. IPI549 ifunyenwe isibophelelo esibambene ngokuphawulekayo kwi-PI3Kγ ene-Kd ye-290 pM kunye > ne-58-fold weaker affinity kwezinye ii-isoform zeClass I PI3K (PI3Kα Kd=17 nM, PI3Kβ Kd=82 nM, PI3Kδ Kd=23 M). Kwi-PI3K-α, -β, -γ, kunye -δ exhomekeke kwii-assays ze-phospho-AKT zeselula, i-IPI549 ibonisa i-PI3K-γ potency egqwesileyo (IC50 = 1.2 nM) kunye nokukhetha ngokuchasene nezinye ii-isoform zeClass I PI3K (> 146-fold). I-Cellular IC50s yeKlasi I PI3Kα (250 nM), PI3Kβ (240 nM), PI3Kγ (1.2 nM), PI3Kδ (180 nM) imiselwe kwi-SKOV-3, 786-O, RAW 264.7, kunye neeseli ze-RAJI ngokulandelelana, ngokulandelanayo, ngokulandelelana. uthintelo lwe-pAKT S473 nge ELISA. Ngaphaya koko, i-IPI549 ithamo ngokuxhomekeka inqanda i-PI3Kγ exhomekeke kwithambo le-macrophage ephuma kwi-macrophage (BMDM). I-IPI549 iphinda ifumaneke ukuba ikhethe ngokuchasene nephaneli ye-80 GPCRs, iziteshi ze-ion, kunye nabathuthi kwi-10 μM [1].

Ithagethi: PI3Kγ,PI3Kβ