GDC-0276

• 常用名: GDC-0276
• 英文名: GDC-0276
• CAS号: 1494581-70-2
• 分子量: 462.58
• 密度: N/A
• 沸点: N/A
• 分子式: C₂₄H₃₁FN₂O₄S
• 熔点: N/A
• 闪点: N/A

GDC-0276用途

GDC-0276 是一种有效的、选择性的、可逆的口服活性 NaV1.7 抑制剂,其 IC50 值为 0.4 nM。GDC-0276 耐受性良好,显现良好的药代动力学特征。GDC-0276 有潜力用于治疗疼痛以及解决现有止痛药物缺陷,如成瘾和脱靶副作用的相关研究。

GDC-0276名称

• 英文名: GDC-0276

GDC-0276生物活性

• 描述: GDC-0276 是一种有效的、选择性的、可逆的口服活性 NaV1.7 抑制剂,其 IC50 值为 0.4 nM。GDC-0276 耐受性良好,显现良好的药代动力学特征。GDC-0276 有潜力用于治疗疼痛以及解决现有止痛药物缺陷,如成瘾和脱靶副作用的相关研究。
• 相关类别:
  信号通路 >> 跨膜转运 >> 钠通道
  研究领域 >> 神经疾病
• 靶点实验:

  IC50:0.4 nM (NaV1.7 Electrophysiology)[1]

• 体内研究: GDC-0276(口服；0.5-5 mg/kg)显示14C的富集,观察到的比活性为22.6μCi/mg。尿中未检测到GDC-0276；然而,尿中的代谢物在14C中富集,观察到的比活性为19.6μCi/mg[3]。动物模型：6只药物纯比格犬1组4只狗(n=2只/性别)和2组2只BDC狗(n=2只雄性)[3]剂量：0.5、1、2、3、4、5 mg/kg给药：口服给药结果：1组和2组的平均比活性分别为12.2μCi/mg(24%富集)(n=4只动物)和23.5μCi/mg(139%富集)(n=2只动物),分别是。
• 参考文献:

  [1]. Rothenberg ME, et al. Safety, Tolerability, and Pharmacokinetics of GDC-0276, a Novel NaV1.7 Inhibitor, in a First-in-Human, Single- and Multiple-Dose Study i

  [2]. Steven J. McKerrall, et al. Nav1.7 inhibitors for the treatment of chronic pain. Bioorganic & Medicinal Chemistry Letters (2018)

  [3]. Takahashi RH,et al.Unequal Absorption of Radiolabeled and Nonradiolabeled Drug from the Oral Dose Leads to Incorrect Estimates of Drug Absorption and Circulating Metabolites in a Mass Balance Study.Drug Metab Lett. 2019;13(1):37-44.

GDC-0276物理化学性质

• 分子式: C₂₄H₃₁FN₂O₄S
• 分子量: 462.58
• InChIKey: PTCBNPULJWGSML-UHFFFAOYSA-N
• SMILES: O=C(NS(=O)(=O)N1CCC1)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F

GDC-0276靶点实验

查看更多实验

实验名称：Inhibition of human Nav1.5/beta1/2 transfected in HEK293-A cells assessed as inhibiti... 来源：ChEMBL 靶标：Sodium channel protein type 5 subunit alpha External Id：CHEMBL5252388

实验名称：Selectivity index, ratio of IC50 for inhibition of human Nav1.5 expressed in HEK293 c... 来源：ChEMBL 靶标：N/A External Id：CHEMBL4322002

实验名称：Inhibition of human Nav1.1/beta1/2 transfected in HEK293-A cells assessed as inhibiti... 来源：ChEMBL 靶标：Sodium channel protein type 1 subunit alpha External Id：CHEMBL5252387

实验名称：Selectivity index, ratio of IC50 for inhibition of human Nav1.2 expressed in HEK293 c... 来源：ChEMBL 靶标：N/A External Id：CHEMBL4321999

实验名称：Inhibition of human Nav1.7/beta1/2 transfected in HEK293-A cells assessed as inhibiti... 来源：ChEMBL 靶标：Sodium channel protein type 9 subunit alpha External Id：CHEMBL5252384

实验名称：Selectivity index, ratio of IC50 for inhibition of human Nav1.1 expressed in HEK293 c... 来源：ChEMBL 靶标：N/A External Id：CHEMBL4321998

实验名称：Inhibition of human Nav1.6 expressed in HEK293 cells by electrophysiology assay 来源：ChEMBL 靶标：Sodium channel protein type 8 subunit alpha External Id：CHEMBL4321996

实验名称：Inhibition of human Nav1.5 expressed in HEK293 cells by electrophysiology assay 来源：ChEMBL 靶标：Sodium channel protein type 5 subunit alpha External Id：CHEMBL4321995

实验名称：Selectivity index, ratio of IC50 for inhibition of human Nav1.6 expressed in HEK293 c... 来源：ChEMBL 靶标：N/A External Id：CHEMBL4322003

实验名称：Antinociceptive activity in po dosed FVB hNav1.7 transgenic mouse model of inherited ... 来源：ChEMBL 靶标：Mus musculus External Id：CHEMBL5055732

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