PIB-549

Lub npe tshuaj:

(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

SMILES Code:

O=C(C1=C2N=CC=CN2N=C1N)N[C@H](C3=CC4=C(C(N3C5=CC=CC=C5)=O)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 Key:

XUMALORDVCFWKV-IBGZPJMESA-N

Lo lus tseem ceeb:

PIB 549, 549, 549, 1693758-51-8

Solubility:Soluble hauv DMSO

Cia:0 - 4 ° C rau lub sijhawm luv (hnub mus rau lub lis piam), lossis -20 ° C rau lub sijhawm ntev (hli).

Nqe lus piav qhia:

IPI-549 inhibits PI3Kγ nrog IC50 ntawm 16 nM, nrog> 100-fold selectivity dua lwm cov lipid thiab protein kinases (PI3Kα IC50 = 3.2 μM, PI3Kβ IC50 = 3.5 μM, PI3Kδ IC50> 8.4 μM). IPI549 raug soj ntsuam rau kev ua si thoob plaws txhua chav kawm I PI3K isoforms. Kev sib txuas ntawm IPI549 rau PI3K-γ yog txiav txim siab los ntawm kev ntsuas tus nqi ntawm tus kheej thiab rau PI3K-α, β thiab δ siv qhov sib npaug fluorescent titration. IPI549 tau pom tias yog ib qho zoo kawg nkaus khi rau PI3Kγ nrog Kd ntawm 290 pM thiab> 58-fold tsis muaj zog affinity rau lwm yam Class I PI3K isoforms (PI3Kα Kd = 17 nM, PI3Kβ Kd = 82 nM, PI3Kδ Kd = 23 M). Hauv PI3K-α, -β, -γ, thiab -δ nyob ntawm cov xov tooj ntawm tes phospho-AKT kev soj ntsuam, IPI549 qhia tau zoo heev PI3K-γ potency (IC50 = 1.2 nM) thiab xaiv tawm tsam lwm chav kawm I PI3K isoforms (> 146-fold). Cellular IC50s rau Class I PI3Kα (250 nM), PI3Kβ (240 nM), PI3Kγ (1.2 nM), PI3Kδ (180 nM) yog txiav txim siab hauv SKOV-3, 786-O, RAW 264.7, thiab RAJI hlwb, raws li kev soj ntsuam. inhibition ntawm pAKT S473 los ntawm ELISA. Tsis tas li ntawd, IPI549 koob tshuaj nyob ntawm inhibits PI3Kγ nyob ntawm cov pob txha pob txha-derived macrophage (BMDM) tsiv teb tsaws. IPI549 kuj pom tias muaj kev xaiv tiv thaiv lub vaj huam sib luag ntawm 80 GPCRs, ion channels, thiab thauj khoom ntawm 10 μM[1].

Hom phiaj: PI3Kγ, PI3Kβ