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Cat No.
CEI-0333
Description
OC000459 is an indole-acetic acid derivative that potently displaces PGD2 from human recombinant D prostanoid receptor 2 with Ki of 13 nM, rat recombinant D prostanoid receptor 2 with Ki of 3 nM, and human native D prostanoid receptor 2 with Ki of 4 nM.
Alias
OC-000459, OC 000459
Synonyms
OC-000459, OC 000459
CAS No.
851723-84-7
Targets
human recombinant DP2
Chemical Name
5-?fluoro-?2-?methyl-?3-?(2-?quinolinylmethyl)-?1H-?indole-?1-?acetic acid
M.Wt
348.4
Purity
0.99
Solubility
DMSO:PBS(1:1) 0.5 mg/mL
Storage
2 years -20centigrade Powder
In vitro
VX-950 is a potent, small molecule, peptidomimetic inhibitor of the hepatitis C virus (HCV) NS3.4A serine protease. Although competitive with the peptide substrate in the active site, VX-950 exhibits apparent noncompetitive inhibition as a result of its tight binding properties and time-dependent inhibition mechanism. Incubation of the HCV Con1 subgenomic replicon cells with VX-950 results in a concentration-dependent decline of the HCV RNA level. The dominant resistance mutation observed against VX-950 was a substitution of Ala156 in the HCV NS3 protease domain with a serine. VX-950 demonstrates excellent antiviral activity both in genotype 1b HCV replicon cells with IC50 of 354 nM and in human fetal hepatocytes infected with genotype 1a HCV-positive patient sera with IC50 of 280 nM. VX-950 forms a covalent but reversible complex with the genotype 1a HCV NS3-4A protease in a slow-on, slow-off process with a steady-state inhibition constant Ki of 7 nM. [1][2]
Clinical Trials
As a potent and selective CRTH2 antagonist, OC000459 shows promise as a novel oral treatment for asthma and related disorders. In the PP population, the forced expiratory volume mean changes are 9.2% and 1.8%, respectively (P=0.037). OC000459 also improves the night-time symptom scores. In steroid-na?ve asthmatic patients, there is a 25.4% (95% CI 5.1-45.6%) reduction in the LAR area under the curve (AUC) for change in forced expiratory volume in 1 s with OC000459 compared with placebo (p=0.018) but no effect on the EAR. In adult patients with active, corticosteroid-dependent or corticosteroid-refractory EoE with an 8-week OC000459 treatment, the esophageal eosinophil load decreases significantly, from 114.83 to 73.26 eosinophils per high-power field [(eos/hpf), P = 0.0256], whereas no reduction is observed with placebo (102.80-99.47 eos/hpf, P = 0.870).
