SC-1-151 (Duquesne University)(SC-1-151 (Duquesne University)) - 药物靶点：MAP2K5 x MEK1 x MEK2_在研适应症：肿瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

SC-1-151、SC-1-151 (Duquesne University/Tulane University)

靶点

MAP2K5 x MEK1 x MEK2

作用机制

MAP2K5抑制剂(mitogen-activated protein kinase kinase 5 inhibitors)、MEK1抑制剂(双特异性丝裂原活化蛋白激酶激酶1抑制剂)、MEK2抑制剂(双特异性丝裂原活化蛋白激酶激酶2抑制剂)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

Duquesne University of The Holy Spirit

在研机构

Tulane University Hospital & Clinic

Duquesne University of The Holy Spirit

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 SC-1-151 (Duquesne University) 相关的临床结果

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100 项与 SC-1-151 (Duquesne University) 相关的转化医学

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100 项与 SC-1-151 (Duquesne University) 相关的专利（医药）

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1

项与 SC-1-151 (Duquesne University) 相关的文献（医药）

2022-09-01·Journal of Pineal Research

The role of MEK1/2 and MEK5 in melatonin‐mediated actions on osteoblastogenesis, osteoclastogenesis, bone microarchitecture, biomechanics, and bone formation

Article

作者: Witt‐Enderby, Paula A. ; Carpentieri, Agata R. ; Burow, Matthew E. ; Sola, Veronica M. ; Hoang, Van T. ; Munmun, Fahima ; Mohiuddin, Omair A. ; Bunnell, Bruce A.

AbstractMelatonin, the primary hormone involved in circadian entrainment, plays a significant role in bone physiology. This study aimed to assess the role of MEK1/2 and MEK5 in melatonin‐mediated actions in mouse and human mesenchymal stem cells (MSCs) and on bone using small‐molecule inhibitors and CRISPR/Cas9 knockout approaches. Consistent with in vitro studies performed in mMSCs and hMSCs, nightly (25 mg/kg, i.p., 45 days) injections with PD184352 (MEK1/2 inhibitor) or Bix02189 (MEK5 inhibitor) or SC‐1‐151 (MEK1/2/5 inhibitor) demonstrated that MEK1/2 and MEK5 were the primary drivers underlying melatonin's actions on bone density, microarchitecture (i.e., trabecular number, separation, and connectivity density), and bone mechanical properties (i.e., ultimate stress) through increases in osteogenic (RUNX2, BMP‐2, FRA‐1, OPG) expression and decreases in PPARγ. Furthermore, CRISPR/Cas9 knockout of MEK1 or MEK5 in mMSCs seeded on PLGA scaffolds and placed into critical‐size calvarial defects in Balb(c) mice (male and female) revealed that treatment with melatonin (15 mg/L; p.o., nightly, 90 days) mediates sex‐specific actions of MEK1 and MEK5 in new bone formation. This study is the first to demonstrate a role for MEK1/2 and MEK5 in modulating melatonin‐mediated actions on bone formation in vivo and in a sex‐specific manner.

100 项与 SC-1-151 (Duquesne University) 相关的药物交易

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