IPI-549

Orukọ Kemikali:

(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

KỌỌDỌ 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

Koodu 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

Bọtini InChi:

XUMALORDVCFWKV-IBGZPJMESA-N

Koko-ọrọ:

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

Solubility:Tiotuka ni DMSO

Ibi ipamọ:0 - 4°C fun igba kukuru (ọjọ si awọn ọsẹ), tabi -20°C fun igba pipẹ (osu).

Apejuwe:

IPI-549 ṣe idiwọ PI3Kγ pẹlu IC50 ti 16 nM, pẹlu> 100-fold selectivity lori miiran lipid ati protein kinases (PI3Kα IC50=3.2 μM, PI3Kβ IC50=3.5 μM, PI3Kδ IC50>8.4 μM). IPI549 jẹ iṣiro fun iṣẹ ṣiṣe kọja gbogbo awọn isoforms Kilasi I PI3K. Ibaṣepọ abuda ti IPI549 fun PI3K-γ jẹ ipinnu nipasẹ wiwọn awọn iyewọn onikaluku ati fun PI3K-α, β ati δ ni lilo iwọntunwọnsi fluorescent titration. IPI549 ni a rii pe o jẹ asopo wiwọ ti iyalẹnu si PI3Kγ pẹlu Kd ti 290 pM ati> 58-apa alailagbara fun awọn isoforms Kilasi I PI3K miiran (PI3Kα Kd=17 nM, PI3Kβ Kd=82 nM, PI3Kδ Kd=23 M). Ni PI3K-α, -β, -γ, ati -δ cellular phospho-AKT assays, IPI549 ṣe afihan agbara PI3K-γ to dara julọ (IC50 = 1.2 nM) ati yiyan si awọn isoforms Class I PI3K miiran (> 146-fold). Cellular IC50s fun Kilasi I PI3KA (250 nM), PI3Kβ (240 nM), PI3Kγ (1.2 nM), PI3Kδ (180 nM) ti pinnu ni SKOV-3, 786-O, RAW 264.7, ati awọn sẹẹli RAJI, lẹsẹsẹ, nipasẹ ibojuwo. idinamọ ti pAKT S473 nipasẹ ELISA. Pẹlupẹlu, iwọn lilo IPI549 ni igbẹkẹle ṣe idiwọ ijira macrophage (BMDM) ti o gbẹkẹle PI3Kγ. IPI549 tun rii pe o jẹ yiyan lodi si igbimọ ti 80 GPCRs, awọn ikanni ion, ati awọn gbigbe ni 10 μM[1].

Àfojúsùn: PI3Kγ, PI3Kβ