IPI-549

Inoa Kimia:

(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(C#CC6=CN(C) N=C6)=CC=C4)C

Code 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

Ki InChi:

XUMALORDVCFWKV-IBGZPJMESA-N

Hua'ōlelo:

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

Hiki ke hoʻoheheʻe:Hiki ke hoʻoheheʻe ʻia ma DMSO

Waihona:0 - 4°C no ka wā pōkole (nā lā i nā pule), a i ʻole -20°C no ka wā lōʻihi (mau mahina).

wehewehe:

IPI-549 inhibits PI3Kγ me IC50 o 16 nM, me> 100-fold selectivity ma luna o nā lipid a me ka protein kinases (PI3Kα IC50 = 3.2 μM, PI3Kβ IC50 = 3.5 μM, PI3Kδ IC50> 8.4 μM). Loiloi ʻia ka IPI549 no ka hana ma waena o nā isoforms Class I PI3K. Hoʻoholo ʻia ka pilina paʻa o IPI549 no PI3K-γ ma ke ana ʻana i nā helu pākahi a no PI3K-α, β a me δ me ka hoʻohana ʻana i ka equilibrium fluorescent titration. ʻIke ʻia ʻo IPI549 he mea hoʻopaʻa paʻa paʻa loa iā PI3Kγ me kahi Kd o 290 pM a ʻoi aku ka nāwaliwali o 58-fold no nā isoforms Class I PI3K (PI3Kα Kd=17 nM, PI3Kβ Kd=82 nM, PI3Kδ Kd=23 M). Ma PI3K-α, -β, -γ, a me -δ hilinaʻi cellular phospho-AKT assays, IPI549 hōʻike i ka mana maikaʻi PI3K-γ (IC50 = 1.2 nM) a me ke koho ʻana i nā isoforms Class I PI3K (> 146-fold). Hoʻoholo ʻia nā IC50 kelepona no ka Papa I PI3Kα (250 nM), PI3Kβ (240 nM), PI3Kγ (1.2 nM), PI3Kδ (180 nM) ma SKOV-3, 786-O, RAW 264.7, a me nā pūnaewele RAJI. ka pale ʻana i ka pAKT S473 e ELISA. Eia kekahi, ʻo ka nui o ka IPI549 e kāohi i ka neʻe ʻana o ka macrophage i loaʻa i ka iwi momona (BMDM) hilinaʻi PI3Kγ. ʻIke ʻia ʻo IPI549 e koho e kūʻē i kahi panel o 80 GPCRs, nā kaila ion, a me nā mea lawe ma 10 μM[1].

Pahuhopu: PI3Kγ,PI3Kβ