生物活性

• 描述ERK1 (Extracellular Signal-Regulated Kinase 1) and ERK2 belong to the MAP kinase family. ERK1 and ERK2 are the 2 ERKs which play an important role in the MAPK/ERK cascade. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements^[2]. LY3214996 is a selective inhibitor of ERK1 and ERK2, with IC50 of 5 nM for both enzymes in biochemical assays. LY3214996 inhibits cellular phospho-RSK1 in BRAF and RAS mutant cancer cell lines. Anti-tumor activity of LY3214996 was observed in tumor cells with MAPK pathway alterations including BRAF, NRAS or KRAS mutation^[1]. Another report suggested that LY3214996 may be effective against patient derived RAS-mutant NSCLC cell lines^[3]. In tumor xenograft models, LY3214996 inhibits pharmadynamic biomarker phospho-p90RSK1 in tumors. LY3214996 shows either similar or superior anti-tumor activity as compared to other published ERK inhibitors in BRAF or RAS mutant cell lines and xenograft models. Oral administration of single-agent LY3214996 significantly inhibits tumor growth in vivo and is well tolerated in BRAF or NRAS mutant melanoma, BRAF or KRAS mutant colorectal, lung and pancreatic cancer xenografts or PDX models^[1].
• 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
  NCT02857270	Advanced Cancer ... more >> Metastatic Melanoma Metastatic Non-small Cell Lung Cancer Metastatic Pancreatic Ductal Adenocarcinoma Colorectal Cancer Collapse <<	Phase 1	Recruiting	July 13, 2020	United States, District of Col... more >>umbia Georgetown University Medical Center Not yet recruiting Washington, District of Columbia, United States, 20007 Contact    202-444-2223       Principal Investigator: Stephen V Liu          United States, Florida Florida Cancer Specialists Recruiting Sarasota, Florida, United States, 34232 Contact    9413779993       Principal Investigator: Manish Rajni Patel          United States, Massachusetts Massachusetts General Hospital Recruiting Boston, Massachusetts, United States, 02114 Contact    617-643-3614       Principal Investigator: Ryan Sullivan          United States, New Hampshire Dartmouth Hitchcock Medical Center Not yet recruiting Lebanon, New Hampshire, United States, 03756-0001 Contact    603-650-6344       Principal Investigator: Konstantin Dragnev          United States, Pennsylvania UPMC Hillman Cancer Center Recruiting Pittsburgh, Pennsylvania, United States, 15232-1305 Contact    412-864-7859       Principal Investigator: Timothy F Burns          United States, Tennessee Sarah Cannon Cancer Center Recruiting Nashville, Tennessee, United States, 37203 Contact    615-329-7274       Principal Investigator: SMO Sarah Cannon Research Inst.          Tennessee Oncology PLLC Recruiting Nashville, Tennessee, United States, 37203 Contact    6153297274       Principal Investigator: Johanna Chock Bendell          United States, Texas University of Texas MD Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Contact    713-745-6601       Principal Investigator: Shubham Pant          Australia, New South Wales St Vincent's Hospital Recruiting Sydney, New South Wales, Australia, 2010 Contact    61293555655       Principal Investigator: Anthony Joshua          Australia, Western Australia Linear Clinical Research Ltd Recruiting Nedlands, Western Australia, Australia, 6009 Contact    61861510923       Principal Investigator: Michael J Millward          France Gustave Roussy Recruiting Villejuif Cedex, France, 94805 Contact    33142114385       Principal Investigator: Antoine Hollebecque Collapse <<

• 参考文献

• [1] Abstract 4973: Discovery of LY3214996, a selective and novel ERK1/2 inhibitor with potent antitumor activities in cancer models with MAPK pathway alterations

  [2] Functions of ERK1 and ERK2.

  [3] Abstract 5467: Efficacy of the ERK inhibitor LY3214996 and the PI3K/mTOR inhibitor LY3023414 in patient-derived RAS-mutant NSCLC models