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CC-930的生物活性
CC-930(Tanzisertib) is a selective and potent JNK1/JNK2/JNK3(IC50=61/7/6 nM) inhibitor and is currently under clinical development for fibrotic and infammatory indications.
IC50 Value: 61 nM (JNK1); 7 nM (JNK2); 6 nM (JNK3) [1]
Target: JNK1/2/3
in vitro: Compound 1 (CC-930) showed remarkable selectivity in a panel of 240 kinases, EGFR being the only non-MAP kinase inhibited more than 50% at 3 lM (IC50 = 0.38 lM). It inhibited no receptor at greater than 50% at 10 lM concentration in a panel of 75 receptors, ion channels and neurotransmitter transporters. Finally, when tested against 22 diverse non-kinase enzymes at 10 lM, no inhibition greater than 50% was observed [1]. Incubation with CC-930 prevented the phosphorylation of c-Jun and reduced the stimulatory levels of these cytokines on the release of collagen [2].
in vivo: Inhibition of JNK by CC-930 prevented dermal thickening, myofibroblast differentiation and the accumulation of collagen in a dose-dependent manner in mice challenged with bleomycin and in TSK1 mice. In addition to the prevention of fibrosis, treatment with pharmacologically relevant doses of CC-930 also induced regression of established experimental fibrosis [2]. CC-930 did not affect blood pressure, kidney hypertrophy, glomerular hyperfiltration, podocyte loss, glomerular fibrosis or tubulointerstitial injury in diabetic SHR (spontaneously hypertensive rats). However, CC-930 reduced macrophages and ccl2 mRNA levels in diabetic kidneys [3].
Toxicity: There were no deaths or AEs that led to withdrawal during the study. Fifteen (33%) subjects reported a total of 22 treatment-emergent adverse events (TEAEs). Subject 207 (25-mg CC-930 group) was involved in a road traffic accident 6 days after the dose and was hospitalized. This adverse event was considered as a serious adverse event but not related to the study drug. The severity of all other adverse events was rated as mild [4].
化学信息
| 分子量 | 448.44 | 储存条件 | 参考CoA中推荐的条件进行储存。 |
|---|---|---|---|
| 分子式 | C21H23F3N6O2 | ||
| CAS号 | 899805-25-5 | ||
| 溶剂/溶解度 | 10 mM in DMSO |
