生物活性

• 靶点

  EGFR IC50:0.3nM

  Ephrin Receptor B4 IC50:1.4nM

  HER2 IC50:16nM

  VEGFR IC50:1.5nM

• 描述XL647 is a selective EGFR inhibitor with IC50 values of 0.3nM, 16nM, 1.5nM, 8.7nM and 1.4nM for EGFR, ErbB2, KDR, Flt-4 and EphB4, respectively. XL647 inhibited cellular WT and mutant EGFR phosphorylation with IC50 values of 1nM, 12nM, 5nM, 10nM, 5nM and 74nM for EGFR WT (A431), EGFR WT (pCMV/Lx-1), EGFR L858R (pCMV/Lx-1), EGFR L861Q (pCMV/Lx-1), EGFR WT (pTet-On/Lx-1) and EGFR Variant III (pTet-On/Lx-1), respectively. It inhibitsed cellular proliferation and EGFR pathway activation, including p-AKT and p-ERK, in the erlotinib-resistant H1975 cell line that harbors a double mutation (L858R and T790M) in the EGFR gene. Oral administration of XL647 at doses of 10mg/kg, 30mg/kg and 100mg/kg, once daily for 28 days, dose-dependently inhibited tumor growth in athymic mice xenograft A431 tumors. Similarly, significant tumor growth inhibition by administration of XL647 at dose of 100mg/kg could be observed in severe combined immunodeficient mice subcutaneously implantated with H1975 tumor and nude mice subcutaneously implantated with MDA-MB-231 tumor in mammary fat pad. In vivo efficacy studies showed that XL647 reduced both tumor EGFR signaling and tumor vessel density^[2].
• 作用机制XL647 is a reversible and ATP competitive inhibitor.^[2]

• 动物研究
  剂量	Mice: 7.5 mg/kg , 15 mg/kg[2] (i.p.); 100 mg/kg[1] (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
  NCT01487174	Carcinoma, Non-Small-Cell Lung	Phase 3	Terminated(Kadmon has made a b... more >>usiness decision to terminate the study due to slow enrollment. Note the decision to terminate the study was not related to safety issues) Collapse <<	-	United States, Connecticut ... more >> Yale Cancer Center New Haven, Connecticut, United States, 06519 United States, New Mexico San Juan Oncology Associates Farmington, New Mexico, United States, 87401 Collapse <<
  NCT02154529	HER-2 Positive Breast Cancer ... more >> Metastatic Malignant Neoplasm to Brain Collapse <<	Phase 1 Phase 2	Terminated(Sponsor closed the ... more >>study in order to review data from other ongoing tesevatinib oncology studies, and to determine feasibility of continuing this study) Collapse <<	-	United States, California ... more >> UC San Diego Moores Cancer Center La Jolla, California, United States, 92093 United States, Indiana Indiana University Health Melvin and Bren Simon Cancer Center Indianapolis, Indiana, United States, 46202 United States, Massachusetts Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02215 United States, New Mexico San Juan Oncology Farmington, New Mexico, United States, 87401 United States, New York Laura and Isaac Perlmutter Cancer Center @ NYU Langone New York, New York, United States, 10016 United States, Tennessee Sarah Cannon Research Institute Nashville, Tennessee, United States, 37203 Collapse <<
  NCT02616393	Non-Small Cell Lung Cancer ... more >> Leptomeningeal Metastases Brain Metastases Collapse <<	Phase 2	Active, not recruiting	-	United States, California ... more >> Beverly Hills Cancer Center Beverly Hills, California, United States, 90211 John Wayne Cancer Institute Santa Monica, California, United States, 90404 United States, Colorado University of Colorado Cancer Center Aurora, Colorado, United States, 80045 United States, District of Columbia Georgetown University Medical Center Washington, District of Columbia, United States, 20007 United States, Tennessee Sarah Cannon Research Institute Nashville, Tennessee, United States, 37203 United States, Texas UT M.D. Anderson Cancer Center Houston, Texas, United States, 77030 Collapse <<

• 更多
• 参考文献

• [1] Gendreau SB, Ventura R, et al. Inhibition of the T790M gatekeeper mutant of the epidermal growth factor receptor by EXEL-7647. Clin Cancer Res. 2007 Jun 15;13(12):3713-23.

  [2] Gendreau SB, Ventura R, Keast P, Laird AD, Yakes FM, Zhang W, Bentzien F, Cancilla B, Lutman J, Chu F, Jackman L, Shi Y, Yu P, Wang J, Aftab DT, Jaeger CT, Meyer SM, De Costa A, Engell K, Chen J, Martini JF, Joly AH. Inhibition of the T790M gatekeeper mutant of the epidermal growth factor receptor by EXEL-7647. Clin Cancer Res. 2007 Jun 15;13(12):3713-23. doi: 10.1158/1078-0432.CCR-06-2590. PMID: 17575237.