Edicotinib

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

Edicotinib (JNJ 40346527, PRV 6527) 是一种有效的、选择性的、口服生物可利用的 CSF-1R 抑制剂，IC50 为 3.2 nM；显示出对 KIT 和 FLT3 的弱亲和力（IC50 分别为 20 nM 和 190 nM）。

Edicotinib (JNJ 40346527, PRV 6527) is a potent, selective, orally bioavailable CSF-1R inhibitor with IC50 of 3.2 nM; shows weak affinity for KIT and FLT3 (IC50= 20 nM and 190 nM, respectively); reduces the levels of EMT-associated genes, stem cell markers and chemoresistance genes, produces strong chemo-sensitizing effects in vitro and in vivo.Rheumatoid Arthritis Phase 2 Clinical(In Vitro):Edicotinib (0.1 nM-1μM; 24 hours) Leads to a dose-dependent decrease of CSF1R activation and a concurrent reduction of ERK1 and ERK2 phosphorylation. The dose response curve shows the effect of JNJ-527 on CSF1R and ERK1/2, and the IC50 values are 18.6 nM and 22.5 nM for CSF1R and ERK1/2, respectively.(In Vivo):Edicotinib (oral gavage; 3, 10, 30 and 100 mg/kg; 5 days) significantly inhibits microglial proliferation in ME7 mice. It diminishes the number of microglia (total CD45+CD11b+ cells) only at the highest dose tested of 100 mg/kg, and JNJ-527 depletes up to 50% of patrolling blood monocytes at every dose tested (CD45+CD11bhighLy6Cintermediate/lowcells) with only a tendency for a reduction in the proportion of inflammatory monocytes (Ly6C high cells) at 100 mg/kg.Edicotinib exhibits a good pharmacokinetic/pharmacodynamics (PK/PD) profile, the microglial proliferation data shows an EC50 of 196/ml and 69 ng/g calculated from plasmatic and brain compound concentration, respectively.Edicotinib (oral gavage; 30 mg/kg; 33 days) significantly reduces the density of microglia in CA1 of the hippocampus of ME7-prion mice (PU.1+ cells) by up to 30%. And the expression of IL-1β is also reduced,but not other inflammatory cytokines.

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Animal Model:C57BL/6 J (Harlan) mice?Dosage:3, 10, 30 and 100 mg/kg; 5 days Administration:Oral gavage Result:Did not affect microglial numbers when administered under 100 mg/kg.Animal Model:C57BL/6 J (Harlan) mice?Dosage:30 mg/kg; 33 days Administration:Oral gavage Result:Limited microglial expansion and attenuated behavioural deficits in ME7-prion mice.

JNJ 40346527 | PRV 6527

Tyrosine Kinase

CSF1R

CSF1R

Inflammation/Immunology

Rheumatoid Arthritis

1142363-52-7

461.61

C27H35N5O2

>98% (HPLC)

DMSO : 16.67 mg/mL 36.11 mM; H2O : < 0.1 mg/mL

O=C(C1=NC(C#N)=CN1)NC2=CC=C(C3CC(C)(C)OC(C)(C)C3)N=C2C4=CCC(C)(C)CC4

4-cyano-N-[2-(4,4-dimethylcyclohex-1-en-1-yl)-6-(2,2,6,6-tetramethyloxan-4-yl)pyridin-3-yl]-1H-imidazole-2-carboxamide

(-20℃)

With Ice Pack

≥ 2 years