MCE 的所有产品仅用作科学研究或药证申报，我们不为任何个人用途提供产品和服务。

Nirogacestat dihydrobromide

CAS No. : 1962925-29-6

MCE 站：Nirogacestat dihydrobromide

产品活性：Nirogacestat dihydrobromide (PF-3084014 dihydrobromide) 是一种有效的，具有口服活性的，可逆的非竞争性的选择性的 γ-secretase 抑制剂，IC₅₀ 为 6.2 nM。Nirogacestat dihydrobromide 抑制 Notch 信号通路，同时*小化胃肠道毒性。可用于研究 Notch 受体依赖性肿瘤。

研究领域：Neuronal Signaling  |  Stem Cell/Wnt  |  Apoptosis

作用靶点：γ-secretase  |  Apoptosis

In Vitro: The IC₅₀ of Nirogacestat (PF-03084014) for γ-secretase enzyme inhibition in cell-free assay for Aβ production using detergent solubilized membranes derived from HeLa cells is determined to be 6.2 nM. When tested for inhibition of Notch receptor cleavage in cellular assays using HPB-ALL cells that harbor mutations in both the heterodimerization and PEST domains in Notch1, the cell IC₅₀ is determined to be 13.3 nM. Nirogacestat causes a significant increase in caspase-3 activities in HPB-ALL and TALL-1 cells as well as an induction of cleaved PARP and cleaved caspase-3 after a 7-day treatment.

In Vivo: Nirogacestat (PF-03084014) shows robust antitumor activity in this model on 14-day twice daily dosing. Tumor growth inhibition is dose dependent, with maximal tumor growth inhibition of ~92% obtained at high dose levels (150 mg/kg). In tumor growth inhibition studies where mice receive repetitive twice daily dosing for more than a week, Nirogacestat is well tolerated at dose levels below 100 mg/kg as no significant weight loss, morbidity, or mortality is observed. When the dose is increased to 150 mg/kg, however, mice have diarrhea and show weight loss (10-15%) approximately 10 days after compound administration. The body weight of treated animals usually returns to normal if dosing holidays are given, suggesting that the toxicity of Nirogacestat is reversible.

相关产品：MG-132  |  LY294002  |  Doxorubicin hydrochloride  |  Bafilomycin A1  |  Paclitaxel  |  Y-27632 dihydrochloride  |  Acetylcysteine  |  Angiotensin II human  |  SP600125  |  5-Fluorouracil  |  Staurosporine  |  Bortezomib  |  Tamoxifen  |  2-Deoxy-D-glucose  |  Gemcitabine  |  Verteporfin  |  Decitabine  |  Actinomycin D  |  Temozolomide  |  BAY 11-7082  |  Etoposide  |  Mitomycin C  |  CCCP  |  DAPT  |  Rote  |  Etomoxir  |  Stattic  |  Docetaxel  |  Fulvestrant

品牌介绍:
•   MCE (MedChemExpress) 拥有数百种全球独家化合物，我们致力于为全球科研客户提供*新*全的高品质小分子活性化合物；
•   10,000 多种高选择性抑制剂、激动剂涉及各热门信号通路及疾病领域；
•   设有专业的实验中心和严格的质控、验证体系；
•   提供 LC/MS、NMR、HPLC、手性分析、元素分析等各项质检报告，确保产品的高纯度、高品质；
•   产品的生物活性多经各国客户实验验证；
•   Nature, Cell, Science 等多种期刊及制药收录了MCE客户的科研成果；
•   专业团队跟踪*新的制药及生命科学研究进展，为您提供全球*新的活性化合物；
•   与世界各大制药公司及知名科研机构建立了长期的合作。