IPI-549

Ingoa matū:

(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

Waehere 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

Waehere 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

Kī InChi:

XUMALORDVCFWKV-IBGZPJMESA-N

Kupumatua:

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

Wairewa:Wairewa i roto i te DMSO

Rokiroki:0 - 4°C mo te wa poto (ra ki nga wiki), -20°C ranei mo te wa roa (marama).

Whakaahuatanga:

Ka whakakorehia e te IPI-549 te PI3Kγ me te IC50 o 16 nM, me te> 100-fold selectivity i runga i etahi atu lipid me te protein kinases (PI3Kα IC50 = 3.2 μM, PI3Kβ IC50 = 3.5 μM, PI3Kδ IC50> 8.4 μM). Ka aromatawaihia te IPI549 mo nga mahi puta noa i nga momo ahua I PI3K katoa. Ko te hononga hono o te IPI549 mo te PI3K-γ ka whakatauhia ma te ine i nga reiti takitahi me te mo te PI3K-α, β me te δ ma te whakamahi i te equilibrium fluorescent titration. Ko te IPI549 ka kitea he here tino piri ki te PI3Kγ me te Kd o te 290 pM me te > 58-tiki he hononga ngoikore mo etahi atu momo ahua I PI3K (PI3Kα Kd = 17 nM, PI3Kβ Kd = 82 nM, PI3Kδ Kd = 23 M). I roto i te PI3K-α, -β, -γ, me te -δ dependent cellular phospho-AKT assays, IPI549 whakaatu pai PI3K-γ mananga (IC50=1.2 nM) me te whiriwhiri ki etahi atu Class I PI3K isoforms (>146-fold). Ko nga IC50 pukoro mo te Class I PI3Kα (250 nM), PI3Kβ (240 nM), PI3Kγ (1.2 nM), PI3Kδ (180 nM) kua whakatauhia i roto i te SKOV-3, 786-O, RAW 264.7, me nga pūtau RAJI, ma te aroturuki. te aukati i te pAKT S473 na ELISA. I tua atu, ko te horopeta IPI549 e aukati ana i te PI3Kγ e whakawhirinaki ana ki te hekenga macrophage (BMDM) i ahu mai i te hinu wheua wheua. Ka kitea ano te IPI549 ki te whiriwhiri ki te roopu o nga GPCR 80, nga awa katote, me nga kaikawe i te 10 μM[1].

Whāinga: PI3Kγ,PI3Kβ