"目录号: HY-14761
MAPK/ERK Pathway-
AS 602801 是一种ATP竞争性的JNK抑制剂，作用于JNK1，JNK2和JNK3，IC50分别为 80 nM，90 nM 和 230 nM。
JNK
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生物活性
Description
AS 602801 is an ATP-competitiveJNKinhibitor withIC50of 80 nM, 90 nM, and 230 nM forJNK1,JNK2, andJNK3, respectively.
IC50& Target
IC50: 80 nM (JNK1), 90 nM (JNK2), 230 nM (JNK3)[1]
In Vitro
AS 602801 (AS602801) treatment induces cell death and accordingly decreased the number of viable cells in all three cell lines in a dose-dependent manner, suggesting that AS 602801 may have selective cytotoxic activity against neoplastic cells. AS 602801 exhibits cytotoxicity against both serum-cultured non-stem cancer cells and cancer stem cells derived from human pancreatic cancer, non-small cell lung cancer, ovarian cancer and glioblastoma at concentrations that did not decrease the viability of normal human fibroblasts. AS 602801 also inhibits the self-renewal and tumor-initiating capacity of cancer stem cells surviving AS 602801 treatment[2].
In Vivo
Treatment of nude mice bearing xenografts biopsied from women with endometriosis (BWE) with 30 mg/kg AS 602801 (AS602801) causes 29% regression of lesion. Medroxyprogesterone acetate (MPA) or progesterone (PR) alone did not cause regression of BWE lesions, but combining 10 mg/kg AS 602801 with MPA caused 38% lesion regression. In human endometrial organ cultures (from healthy women), treatment with AS 602801 or MPA reduced matrix metalloproteinase-3 (MMP-3) release into culture medium. In organ cultures established with BWE, PR or MPA failed to inhibit MMP-3 secretion, whereas AS 602801 alone or MPA + AS 602801 suppresses MMP-3 production. In an autologous rat endometriosis model, AS 602801 causes 48% regression of lesions compared to GnRH antagonist Antide (84%). AS 602801 reduces inflammatory cytokines in endometriotic lesions, while levels of cytokines in ipsilateral horns are unaffected. Furthermore, AS 602801 enhances natural killer cell activity, without apparent negative effects on uterus[3].
References
[1].Messoussi A, et al. Recent progress in the design, study, and development of c-Jun N-terminal kinase inhibitors as anticanceragents. Chem Biol. 2014 Nov 20;21(11):1433-43.
[2].Okada M, et al. The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo. Oncotarget. 2016 May 10;7(19):27021-32.
[3].Palmer SS, et al. Bentamapimod (JNK Inhibitor AS602801) Induces Regression of Endometriotic Lesions in Animal Models. Reprod Sci. 2016 Jan;23(1):11-23.