IP-549

Aha kemịkalụ:

(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

Koodu Ọchịchọ:

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

Igodo InChi:

XUMALORDVCFWKV-IBGZPJMESA-N

Okwu:

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

Solubility:Soluble na DMSO

Nchekwa:0 - 4 Celsius C maka obere oge (ụbọchị ruo izu), ma ọ bụ -20 Celsius maka ogologo oge (ọnwa).

Nkọwa:

IPI-549 na-egbochi PI3Kγ na IC50 nke 16 nM, yana> 100-fold selectivity na ndị ọzọ lipid na protein kinases (PI3Kα IC50 = 3.2 μM, PI3Kβ IC50 = 3.5 μM, PI3Kδ IC50>8.4 μM). A na-enyocha IPI549 maka mmemme n'ofe klaasị I PI3K isoform niile. A na-ekpebi njikọ chiri anya nke IPI549 maka PI3K-γ site n'ịtụ ọnụ ahịa nke onye ọ bụla yana maka PI3K-α, β na δ site na iji titration fluorescent nha nhata. Achọpụtara IPI549 ka ọ bụrụ ihe ejikọtara nke ọma na PI3Kγ nwere Kd nke 290 pM yana> mmekọrịta na-esighi ike nke okpukpu 58 maka isoforms Klas I PI3K ndị ọzọ (PI3Kα Kd=17 nM, PI3Kβ Kd=82 nM, PI3Kδ Kd=23 M). Na nyocha PI3K-α, -β, -γ, na -δ cellular phospho-AKT nyocha, IPI549 na-egosipụta ike PI3K-γ dị mma (IC50 = 1.2 nM) na nhọrọ megide ndị ọzọ Klas I PI3K isoforms (> 146-fold). Cellular IC50s maka Klas I PI3KA (250 nM), PI3Kβ (240 nM), PI3Kγ (1.2 nM), PI3Kδ (180 nM) na-ekpebi na SKOV-3, 786-O, RAW 264.7, na sel RAJI, n'otu n'otu, site na nlekota oru. Mgbochi nke pAKT S473 site na ELISA. Ọzọkwa, dose IPI549 dabere na-egbochi mbugharị macrophage (BMDM) dabere na ụmị ọkpụkpụ PI3Kγ. A na-ahụkwa IPI549 ka ọ na-ahọrọ megide otu panel nke GPCR 80, ọwa ion, na ndị na-ebugharị na 10 μM[1].

Ebumnuche: PI3Kγ, PI3Kβ