生物活性

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  p38 MAPKα IC50:7nM

  p38 MAPKβ IC50:3nM

• 描述p38α mitogen-activated protein kinase (MAPK) is activated in cancer cells in response to environmental factors, oncogenic stress, radiation, and chemotherapy. p38α MAPK phosphorylates a number of substrates, including MAPKAP-K2 (MK2), and regulates the production of cytokines in the tumor microenvironment, such as TNF-α, interleukin-1β (IL-1β), IL-6, and CXCL8 (IL-8)^[3]. LY2228820 is a novel and effective p38α MAPK inhibitor with an IC₅₀ value of 7 nM in cell free assay. To assess p38α activity in cells more directly, RAW 264.7 cells were treated with LY2228820. It inhibited p38α and the level of pMK2 (phospho-MAPKAP-K2) with IC₅₀s of 7 nM and 34.3 nM, respectively. LY2228820 was orally dosed in Balb/c mice followed by iv LPS administration after 2 h. And the threshold minimum 50% effective dose (TMED₅₀) was less than 1 mg/kg. In the rat CIA (collagen induced arthritis) model, LY2228820 effectively acting on foot swelling, bone erosion, and cartilage destruction, with the TMED₅₀ of 1.5 mg/kg^[4].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  A-2780	1 μM	Function assay	-	reduces tumor-driven cord formation	23335506
  A549	~20 μM	Function assay	-	inhibits LPS-induced CXCL8 production with IC50 of 144.9 nM	24356814
  CD14+	~800 nM	Function assay	-	inhibits osteoclastogenesis from CD14 positive cells	18397345

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• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02860780	Advanced Cancer ... more >> Metastatic Cancer Colorectal Cancer Non-small Cell Lung Cancer Collapse <<	Phase 1	Completed	-	United States, North Carolina ... more >> Carolinas Medical Center Charlotte, North Carolina, United States, 28204 United States, Tennessee Sarah Cannon Research Institute SCRI Nashville, Tennessee, United States, 37203 Germany For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Köln, Germany, 50937 Collapse <<
  NCT01393990	Advanced Cancer	Phase 1	Completed	-	United States, Minnesota ... more >> For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Rochester, Minnesota, United States United States, Texas For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. San Antonio, Texas, United States Collapse <<
  NCT02364206	Adult Glioblastoma	Phase 1 Phase 2	Active, not recruiting	June 2019	France ... more >> CHU Amiens Sud-Salouel Amiens, France Institut Bergonié Bordeaux, France Centre François Baclesse Caen, France Centre Jean Perrin Clermont-Ferrand, France Centre Georges François Leclerc Dijon, France Centre Paul Strauss Strasbourg, France Collapse <<

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