生物活性

• 靶点

  Smo IC50:2.5nM

  Smo (mouse) IC50:1.3nM

• 描述Smoothened (Smo) is a transmembrane protein that serves as a key activator of the hedgehod (Hh) signaling pathway. LDE225 is a potent and selective Smo antagonist with IC50 values of 1.3 and 2.5nM for mouse and human, respectively^[6]. It is tightly bound to human, mouse, and rat plasma proteins (99%), but moderately bound to monkey (85%) and dog (77%) plasma proteins. The combination of LDE225 (20μM) and nilotinib (2μM) more efficiently inhibited the outgrowth of BaF3 cells expressing wt-BCRABL and BCR-ABL mutants as compared to cells treated with either agent alone^[4]. In the mouse subcutaneous Ptch^+/-p53^-/- medulloblastoma allograft model, daily oral administration of LDE225 diphosphate salt (5, 10, or 20mg/kg/day) for 13 days significantly inhibited tumor growth with T/C values of 33%, 51%, and 83%, respectively, as compared to vehicle-treated controls. A single oral dose of LDE225 diphosphate salt (5, 10, or 20mg/kg/day) inhibited Gli1mRNA expression in the mouse medulloblastoma model at a dose- and time-dependent manner^[5].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  769-P	~5 μM	Growth inhibitory assay	-	IC50=2-3 μM	25093491
  786-O	~5 μM	Growth inhibitory assay	-	IC50=2-3 μM	25093491
  786-O SuR	~5 μM	Growth inhibitory assay	-	IC50=2-3 μM	25093491

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• 动物研究
  剂量	Mice: 20 mg/kg[3] (p.o.), 80 mg/kg[4] (p.o.)
  给药途径	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
  NCT02371967	-	-	Active, not recruiting	August 29, 2020	Sweden ... more >> SU/Sahlgrenska, Hudkliniken Göteborg, Sweden, 41345 Skånes Universitetssjukhus; Hudkliniken Lund, Sweden, 222 41 Radiumhemmet Solna, Sweden, 171 64 Norrlands universitetssjukhus; Onkologkliniken Umeå, Sweden Collapse <<
  NCT02129101	Chronic Myelomonocytic Leukemi... more >>a de Novo Myelodysplastic Syndrome Essential Thrombocythemia Myelodysplastic Syndrome Myelodysplastic/Myeloproliferative Neoplasm Polycythemia Vera Previously Treated Myelodysplastic Syndrome Primary Myelofibrosis Recurrent Adult Acute Myeloid Leukemia Recurrent Childhood Acute Myeloid Leukemia Untreated Adult Acute Myeloid Leukemia Collapse <<	Phase 1	Active, not recruiting	October 2018	United States, Minnesota ... more >> Mayo Clinic Rochester, Minnesota, United States, 55905 Collapse <<
  NCT03434262	Anaplastic Astrocytoma ... more >> Anaplastic Ependymoma Anaplastic Ganglioglioma Anaplastic Meningioma Anaplastic Oligodendroglioma Pleomorphic Xanthoastrocytoma, Anaplastic Atypical Teratoid/Rhabdoid Tumor Brain Cancer Brain Tumor Central Nervous System Neoplasms Choroid Plexus Carcinoma CNS Embryonal Tumor With Rhabdoid Features Ganglioneuroblastoma of Central Nervous System CNS Tumor Embryonal Tumor of CNS Ependymoma Glioblastoma Glioma Glioma, Malignant Medulloblastoma Medulloblastoma; Unspecified Site Medulloepithelioma Neuroepithelial Tumor Neoplasms Neoplasms, Neuroepithelial Papillary Tumor of the Pineal Region (High-grade Only) Pediatric Brain Tumor Pineal Parenchymal Tumor of Intermediate Differentiation (High-grade Only) Pineoblastoma Primitive Neuroectodermal Tumor Recurrent Medulloblastoma Refractory Brain Tumor Neuroblastoma. CNS Glioblastoma, IDH-mutant Glioblastoma, IDH-wildtype Medulloblastoma, Group 3 Medulloblastoma, Group 4 Glioma, High Grade Neuroepithelial Tumor, High Grade Medulloblastoma, SHH-activated and TP53 Mutant Medulloblastoma, SHH-activated and TP53 Wildtype Medulloblastoma, Chromosome 9q Loss Medulloblastoma, Non-WNT Non-SHH, NOS Medulloblastoma, Non-WNT/Non-SHH Medulloblastoma, PTCH1 Mutation Medulloblastoma, WNT-activated Ependymoma, Recurrent Glioma, Recurrent High Grade Glioma, Recurrent Malignant Embryonal Tumor, NOS Glioma, Diffuse Midline, H3K27M-mutant Embryonal Tumor With Multilayered Rosettes (ETMR) Ependymoma, NOS, WHO Grade III Ependymoma, NOS, WHO Grade II Medulloblastoma, G3/G4 Ependymoma, RELA Fusion Positive Collapse <<	Phase 1	Recruiting	March 2025	United States, Tennessee ... more >> St. Jude Children's Research Hospital Recruiting Memphis, Tennessee, United States, 38105 Contact: Tabatha E. Doyle, RN    901-595-2544    tabatha.doyle@stjude.org    Principal Investigator: Giles W. Robinson, MD Collapse <<

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