IP-549

Magaca Kiimikada:

(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

Koodhka dhoola cadeynta:

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

Koodhka 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

Furaha InChi:

XUMALORDVCFWKV-IBGZPJMESA-N

Ereyga muhiimka ah:

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

Xalka:Ku milmay DMSO

Kaydinta:0 - 4°C muddo gaaban (maalmo ilaa toddobaadyo), ama -20°C muddo dheer (bilo).

Sharaxaad:

IPI-549 waxay xannibaysaa PI3Kγ IC50 ee 16 nM, oo leh> 100-laab xulashada lipid iyo protein kinases kale (PI3Kα IC50=3.2 μM, PI3Kβ IC50=3.5 μM, PI3Kδ IC50>8.4 μM). IPI549 waxaa lagu qiimeeyaa nashaadaadka dhamaan qaybaha I ee PI3K. Xidhiidhka xidhitaanka ee IPI549 ee PI3K-γ waxaa lagu go'aamiyaa iyadoo la cabbirayo heerarka joogtada ah ee shakhsi ahaaneed iyo PI3K-α, β iyo δ iyadoo la adeegsanayo titration fluorescent dheellitiran. IPI549 waxaa lagu ogaadey inay si cajiib ah ugu dhejisan tahay PI3Kγ oo leh Kd 290 pM ah iyo> 58-laab daciifnimo ee isku xirnaanta kale ee Class I PI3K (PI3Kα Kd=17 nM, PI3Kβ Kd=82 nM, PI3Kδ Kd=23 M). PI3K-α, -β, -γ, iyo -δ-ku-tiirsanaanta phospho-AKT ee gacanta, IPI549 waxay muujinaysaa awoodda PI3K-γ heer sare ah (IC50 = 1.2 nM) iyo xulashada ka soo horjeeda kuwa kale ee I PI3K isoforms (> 146-laab). Cellular IC50s ee fasalka I PI3KA (250 nM), PI3Kβ (240 nM), PI3Kγ (1.2 nM), PI3Kγ (180 nM) waxaa lagu go'aamiyaa SKOV-3, 786-O, RAW 264.7, iyo unugyada RAJI, siday u kala horreeyaan, Joojinta pAKT S473 ee ELISA. Intaa waxaa dheer, qiyaasta IPI549 waxay si ku-tiirsan u joojisaa socdaalka dhuuxa lafta ku tiirsan ee PI3Kγ (BMDM). IPI549 waxa kale oo la ogaadey in uu ka door biday koox ka kooban 80 GPCRs, kanaalka ion, iyo gaadiidleyda 10 μM[1].

Hadafka: PI3Kγ, PI3Kβ