| Bioactivity | Cobimetinib-d4 hydrochloride is deuterated labeled Cobimetinib (HY-13064). Cobimetinib (GDC-0973, RG7420) is a potent, selective and oral MEK1 inhibitor with an IC50 of 4.2 nM for MEK1. |
| Invitro | 氢、碳和其他元素的稳定重同位素已被纳入药物分子中，主要作为药物开发过程中定量的示踪剂。氘化引起了人们的关注，因为它可能影响药物的药代动力学和代谢谱[1]。Cobimetinib (GDC-0973) 对 888MEL 和 A2058 细胞的 EC50 值分别为 0.2 μM、10 μM。黑色素瘤细胞用 EC50 浓度的 MEK 和 PI3K 抑制剂处理 24 小时 (888MEL：0.05 μM GDC-0973、2.5 μM GDC-0941；A2058：2.5 μM GDC-0973、2.5 μM GDC-0941)[2]。线粒体 OXPHOS 限制了黑色素瘤中 cobimetinib (100 nM) 诱导的细胞死亡，并在 A375 细胞中激活了组成型 MAPK[5]。 MCE has not independently confirmed the accuracy of these methods. They are for reference only. 0 --> Cobimetinib-d4 hydrochloride 相关抗体: |
| In Vivo | 在 NCI-H2122 KRASG12C 突变非小细胞肺癌 (NSCLC) 异种移植模型中，高达 5 mg/kg Cobimetinib (GDC-0973) 处理导致中度 TGI，而 10 mg/kg 接近肿瘤停滞[2]。GDC-0973 和 GDC-0941 每天 (QD) 或每三天 (Q3D) 作为单一药物或组合对 A2058 荷瘤小鼠给药。GDC-0973 和 GDC-0941 与肿瘤生长抑制相关的群体速率常数分别为 0.00102 和 0000651 μM-1/h[3]。单剂量 GDC-0973 (1、3 或 10 mg/kg，口服) 后，根据异种移植小鼠中的肿瘤浓度，估计 %pERK 降低的体内 IC50 值为 0.78 (WM-266-4) 和 0.52 μM (A375)[4]。 MCE has not independently confirmed the accuracy of these methods. They are for reference only. |
| Formula | C21H18D4ClF3IN3O2 |
| Molar Mass | 571.80 |
| Transport | Room temperature in continental US; may vary elsewhere. |
| Storage | Please store the product under the recommended conditions in the Certificate of Analysis. |
| Reference | [1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216. [2]. Hoeflich KP, et al. Intermittent administration of MEK inhibitor GDC-0973 plus PI3K inhibitor GDC-0941 triggers robust apoptosis and tumor growth inhibition. Cancer Res. 2012 Jan 1;72(1):210-9. [3]. Corazao-Rozas P, et al. Mitochondrial oxidative phosphorylation controls cancer cell's life and death decisions upon exposure to MAPK inhibitors. Oncotarget. 2016 Feb 29. doi: 10.18632/oncotarget.7790. [4]. Choo EF, et al. PK-PD modeling of combination efficacy effect from administration of the MEK inhibitor GDC-0973 and PI3K inhibitor GDC-0941 in A2058 xenografts. Cancer Chemother Pharmacol. 2013 Jan;71(1):133-43. [5]. Wong H, et al. Bridging the gap between preclinical and clinical studies using pharmacokinetic-pharmacodynamic modeling: an analysis of GDC-0973, a MEK inhibitor. Clin Cancer Res. 2012 Jun 1;18(11):3090-9. |
Cobimetinib-d4 hydrochloride
CAS: F: C21H18D4ClF3IN3O2 W: 571.80
Cobimetinib-d4 hydrochloride is deuterated labeled Cobimetinib (HY-13064). Cobimetinib (GDC-0973, RG7420) is a potent, s
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