生物活性

• 描述Fibroblast growth factor receptors (FGFRs) are involved in cell proliferation, migration, differentiation, and survival. Erdafitinib is an orally bioavailable, small molecule inhibitor of FGFRs with IC50 values of 1.2, 2.5, 3.0, and 5.7 nM for FGFR1, 2, 3, and 4, respectively. It also shows potent inhibitory activity against VEGFR2 kinase with an IC50 value of 36.8 nM. Erdafitinib binds to FGFR1, 2, 3, and 4 with K_d values of 0.24, 2.2, 1.1, and 1.4 nM, respectively. It inhibited the proliferation of cells expressing FGFR1, 3, and 4 with IC50 values of 22.1, 13.2, and 25 nM, respectively. It showed inhibitory activity against BaF3 cells expressing VEGFR2 with an IC50 value of 1.16 μM. Erdafitinib at 100 nM inhibited pFGFR1, pFGFR3, and pFGFR4 in NCI-H1581, KMS-11, and MDA-MB-453 cells, respectively, and pFGFR2 L in SNU-16 cells at a concentration of 30 nM. In mice bearing xenograft tumors derived from SNU-16 gastric cancer cells harboring FGFR2 amplifications, the administration of erdafitinib (10 and 30 mg/kg) for 1 h significantly inhibited FGFR signaling and this effect maintained until 7- and 16-h post-treatment. The treatment of SNU-16 tumor-bearing mice with erdafitinib (10 and 30 mg/kg) for 21 days resulted in tumor growth inhibition of 37.8% and 59.4%, respectively, compared to the vehicle-treated animals^[3].
• 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
  NCT03155620	Advanced Malignant Solid Neopl... more >>asm Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma Childhood Langerhans Cell Histiocytosis Histiocytic Sarcoma Juvenile Xanthogranuloma Malignant Glioma Recurrent Central Nervous System Neoplasm Recurrent Childhood Ependymoma Recurrent Childhood Malignant Germ Cell Tumor Recurrent Childhood Medulloblastoma Recurrent Childhood Non-Hodgkin Lymphoma Recurrent Childhood Rhabdomyosarcoma Recurrent Childhood Soft Tissue Sarcoma Recurrent Ewing Sarcoma Recurrent Glioma Recurrent Hepatoblastoma Recurrent Langerhans Cell Histiocytosis Recurrent Malignant Solid Neoplasm Recurrent Neuroblastoma Recurrent Osteosarcoma Recurrent Peripheral Primitive Neuroectodermal Tumor Recurrent Rhabdoid Tumor Refractory Central Nervous System Neoplasm Refractory Childhood Malignant Germ Cell Tumor Refractory Ewing Sarcoma Refractory Glioma Refractory Hepatoblastoma Refractory Langerhans Cell Histiocytosis Refractory Malignant Solid Neoplasm Refractory Medulloblastoma Refractory Neuroblastoma Refractory Non-Hodgkin Lymphoma Refractory Osteosarcoma Refractory Peripheral Primitive Neuroectodermal Tumor Refractory Rhabdoid Tumor Refractory Rhabdomyosarcoma Rhabdoid Tumor Stage III Osteosarcoma AJCC v7 Stage III Soft Tissue Sarcoma AJCC v7 Stage IV Osteosarcoma AJCC v7 Stage IV Soft Tissue Sarcoma AJCC v7 Stage IVA Osteosarcoma AJCC v7 Stage IVB Osteosarcoma AJCC v7 Wilms Tumor Collapse <<	Phase 2	Recruiting	September 30, 2027	-
  NCT03732703	Relapsed Refractory Multiple M... more >>yeloma Collapse <<	Phase 1 Phase 2	Not yet recruiting	February 10, 2024	United States, Arizona ... more >> Mayo Clinic - Arizona Not yet recruiting Phoenix, Arizona, United States, 85054 United States, California City of Hope Not yet recruiting Duarte, California, United States, 91010 United States, Georgia Emory University Not yet recruiting Atlanta, Georgia, United States, 30322 United States, Massachusetts Massachusetts General Hospital Cancer Center Not yet recruiting Boston, Massachusetts, United States, 02114 Beth Israel Deaconess Not yet recruiting Boston, Massachusetts, United States, 02215 Dana Farber Cancer Institute Not yet recruiting Boston, Massachusetts, United States, 02215 United States, Michigan University of Michigan Health System Not yet recruiting Ann Arbor, Michigan, United States, 48109 Karmanos Cancer Center Not yet recruiting Detroit, Michigan, United States, 48201 United States, Minnesota Mayo Clinic - Minnesota Not yet recruiting Rochester, Minnesota, United States, 55905 United States, Missouri Washington University School of Medicine Division of Medical Oncology Not yet recruiting Saint Louis, Missouri, United States, 63110 United States, New Jersey Hackensack University Medical Center Not yet recruiting Hackensack, New Jersey, United States, 07610 United States, New York Mount Sinai School of Medicine Not yet recruiting New York, New York, United States, 10029 Memorial Sloan Kettering Cancer Center Not yet recruiting New York, New York, United States, 10065 United States, North Carolina Levine Cancer Institute Not yet recruiting Charlotte, North Carolina, United States, 28204 United States, Ohio Ohio State University College of Medicine Not yet recruiting Columbus, Ohio, United States, 43210 United States, Texas UT Southwestern Medical Center Not yet recruiting Dallas, Texas, United States, 75390 United States, Virginia Virginia Cancer Specialists Not yet recruiting Fairfax, Virginia, United States, 22031 Collapse <<
  NCT02421185	Carcinoma, Hepatocellular	Phase 1 Phase 2	Active, not recruiting	February 28, 2019	China ... more >> Changchun, China Guangzhou, China Hangzhou, China Harbin, China Nanjing, China Shanghai, China Korea, Republic of Seoul, Korea, Republic of Taiwan Kaohsiung, Taiwan Tainan, Taiwan Taipei, Taiwan Collapse <<

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• 参考文献

• [1] Perera TPS, Jovcheva E,et al. Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor. Mol Cancer Ther. 2017 Jun;16(6):1010-1020.

  [2] Verstraete M, Debucquoy A, et al. In vitro and in vivo evaluation of the radiosensitizing effect of a selective FGFR inhibitor (JNJ-42756493) for rectal cancer. BMC Cancer. 2015 Dec 16;15:946.

  [3] Perera TPS, Jovcheva E, Mevellec L, et al. Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor. Mol Cancer Ther. 2017;16(6):1010-1020. doi:10.1158/1535-7163.MCT-16-0589