CI-1044

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

CI-1044 是一种有效的、选择性的、口服生物可利用的 PDE4 抑制剂，IC50 为 0.27 uM。

CI-1044 is a potent, selective and orally bioavailable PDE4 inhibitor with IC50 of 0.27 uM, displays high selectivity for PDE4 versus PDE1/3/5, and no PDE4 subtype (4A-D) selectivities; exhibits efficient in vitro inhibition of TNFα release from hPBMC and hWB with IC50 of 0.34 and 0.84 uM, respectively; exhibits potent in vivo activity in antigen-induced eosinophil recruitment in rats (ED50=3.2 mg/kg, p.o.).Asthma Phase 1 Clinical.

CI-1044 is an orally active PDE4 inhibitor with IC50s of 0.29, 0.08, 0.56, 0.09 μM for PDE4A5, PDE4B2, PDE4C2 and PDE4D3, respectively. CI-1044 selectively inhibits PDE4 crude extract from U937 cells with an IC50 value of 0.27±0.02 μM being threefold more potent than rolipram (IC50=0.91±0.14) and tenfold less potent than cilomilast (IC50=0.026±0.007) in the same assay. In the presence of PDE4 inhibitors, the production of TNF-α is dose dependently decreased with mean IC50 values from three separate experiments of 0.31±0.05, 0.26±0.05 and 0.11±0.01 μM, for CI-1044, cilomilast and rolipram, respectively.

TNF-α production is dose-dependently inhibited by CI-1044, rolipram and cilomilast with ID50s of 0.4, 1.4 and 1.6 mg/kg respectively following single oral administration. Following repeated administration with CI-1044, the ID50 value represents 0.5 mg/kg p.o.. CI-1044 plasma levels increase proportionally with doses ranging between 0.1 and 40 mg/kg p.o. (R2=0.878). CI-1044 dose dependently inhibits the accumulation of eosinophils in Bronchoalveolar lavages (BAL) fluids with an ID50 value of 3.25 mg/kg. A single dose treatment with CI-1044 (10 mg/kg, p.o.) 24, 8, 3 or 1 h before the antigen challenge induces 6, 56, 48 and 79% inhibition in the number of eosinophils in BAL.

CI1044

Angiogenesis

PDE

PDE

Inflammation/Immunology

Asthma

197894-84-1

397.438

C23H19N5O2

>98% (HPLC)

DMSO : 125 mg/mL 314.52 mM

Nc1cc2CCN3C(=O)[C@H](NC(=O)c4cccnc4)N=C(c5ccccc5)c(c1)c23

(R)-N-(9-amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-3-yl)nicotinamide

(-20℃)

With Ice Pack

≥ 2 years