IPI-549

Igama Lekhemikhali:

(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

Ikhodi ye-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

Ikhodi ye-InChi:

I-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

I-InChi Key:

XUMALORDVCFWKV-IBGZPJMESA-N

Igama elingukhiye:

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

Ukunyibilika:I-Soluble ku-DMSO

Isitoreji:0 - 4°C isikhathi esifushane (izinsuku ukuya emavikini), noma -20°C isikhathi eside (izinyanga).

Incazelo:

I-IPI-549 ivimbela i-PI3Kγ nge-IC50 ye-16 nM, nge> ukukhetha okuphindwe ka-100 ngaphezu kwamanye ama-lipid namaprotheni kinases (PI3Kα IC50=3.2 μM, PI3Kβ IC50=3.5 μM, PI3Kδ IC50>8.4 μM). I-IPI549 ihlolelwa umsebenzi kuwo wonke ama-isoform e-Class I PI3K. Isibopho esibophezelayo se-IPI549 se-PI3K-γ sinqunywa ngokulinganisa amanani angaguquki angawodwana kanye ne-PI3K-α, β kanye no-δ kusetshenziswa i-equilibrium fluorescent titration. I-IPI549 itholakala iyisibopho esiqine ngendlela emangalisayo ku-PI3Kγ ene-Kd engu-290 pM kanye > nokusondelana okubuthakathaka okuphindwe ka-58 kwamanye ama-isoform e-Class I PI3K (PI3Kα Kd=17 nM, PI3Kβ Kd=82 nM, PI3Kδ Kd=23 M). Ku-PI3K-α, -β, -γ, kanye -δ ekuhlolweni kwe-phospho-AKT yamaselula okuncike, i-IPI549 ibonisa amandla amahle kakhulu e-PI3K-γ (IC50=1.2 nM) nokukhetha ngokumelene namanye ama-isoform e-Class I PI3K (>146-fold). I-Cellular IC50s ye-Class I PI3Kα (250 nM), PI3Kβ (240 nM), PI3Kγ (1.2 nM), PI3Kδ (180 nM) inqunywa ku-SKOV-3, 786-O, RAW 264.7, kanye namaseli e-RAJI, ngokulandelana, ngokulandelana, ukuvinjelwa kwe-pAKT S473 nge ELISA. Ngaphezu kwalokho, umthamo we-IPI549 uvimbela ngokuncika kwe-PI3Kγ ukufuduka kwethambo lomnkantsha-derived macrophage (BMDM). I-IPI549 iphinde itholakale ikhetha ngokumelene nephaneli yama-GPCR angu-80, iziteshi ze-ion, nabathuthi ku-10 μM[1].

Ithagethi: PI3Kγ,PI3Kβ