生物活性

• 描述LCL161 is an IAP family inhibitor which can bind and inhibit both XIAP and cIAP. Treatment with LCL161 could enhance the activity of different proapoptotic signaling pathways^[1]. LCL-161 at concentration of 2μM could induce cIAP degradation and activated downstream NFκB in Eμ-Myc cells^[2]. Treatment with LCL161 at concentration<10μM for 24h did not significantly affect protein level of XIAP protein level as Smac-mimetic treatment did not degrade XIAP, but can still inhibit the activity of XIAP measured by upregulation of cleaved caspases 9 and 3, in H929, MM1R and MM1S cells. LCL161 at concentration<15μM dose-dependently induced cell death of H929 and MM1S cells primarily driven by activation of the extrinsic apoptotic pathway^[3]. Combination of LCL161 (100mg/kg) with nilotinib showed synergistic effects and significantly delayed the onset of disease recurrence in a BCR-ABL-positive leukemia model^[1].
• 作用机制LCL-161 is a SMAC mimetic which can both disengage IAPs from caspases and induce proteasomal degradation of cIAP-1 and -2.^[2]
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  human AGS cells	2.5 μM	Apoptosis assay	5 days	Induction of sensitization of human AGS cells to conatumumab-induced apoptosis assessed as cell viability at 2.5 uM after 5 days by MTS assay	24093940
  human BxPC3 cells	3.3 μM	Cytotoxic assay	5 days	Potentiation of conatumumab-induced cytotoxicity against human BxPC3 cells at 3.3 uM after 5 days by MTS assay	24083782
  human Capan1 cells	2.5 μM	Cytotoxic assay	5 days	Potentiation of conatumumab-induced apoptosis in human Capan1 cells at 2.5 uM after 5 days by MTS assay	24093940

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• 动物研究
  剂量	Mice: 10 mg/kg[3] (i.p.); 75 mg/kg[4] (p.o.)
  给药途径	i.p., p.o.

• 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
  NCT02098161	Leukemia	Phase 2	Recruiting	December 2020	United States, Texas ... more >> University of Texas MD Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Collapse <<
  NCT03111992	Multiple Myeloma	Phase 1	Recruiting	May 27, 2020	United States, Arizona ... more >> Novartis Investigative Site Recruiting Phoenix, Arizona, United States, 85054 United States, Tennessee Novartis Investigative Site Recruiting Nashville, Tennessee, United States, 37203 Contact: Kimberly Cox    615-329-7413    Kimberly.Cox3@scresearch.net    Principal Investigator: Jesus G. Berdeja          Canada, Quebec Novartis Investigative Site Recruiting Montreal, Quebec, Canada, H3T 1E2 Germany Novartis Investigative Site Recruiting Heidelberg, Germany, 69120 Novartis Investigative Site Recruiting Kiel, Germany, 24105 Italy Novartis Investigative Site Recruiting Milano, MI, Italy, 20133 Spain Novartis Investigative Site Recruiting Salamanca, Castilla Y Leon, Spain, 37007 Novartis Investigative Site Recruiting Madrid, Spain, 28006 Switzerland Novartis Investigative Site Recruiting Locarno, Switzerland, 6600 Collapse <<
  NCT02890069	Colorectal Cancer, Non-small C... more >>ell Lung Carcinoma (Adenocarcinoma), Triple Negative Breast Cancer, Renal Cell Carcinoma Collapse <<	Phase 1	Recruiting	December 19, 2019	-

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