Ravoxertinib (GDC-0994)ERK 抑制剂

产品简介

Ravoxertinib (GDC-0994) 是可口服的ERK 激酶抑制剂，抑制ERK1和ERK2的IC50分别为 6.1 和 3.1 nM。

产品特性

CAS：1453848-26-4

英文名称：Ravoxertinib

别名：GDC-0994;ERK抑制剂;GDC0994;

分子式：C₂₁H₁₈ClFN₆O₂

分子量：439.85

Smiles：Cn1nccc1Nc1nccc(n1)-c1ccn([C@H](CO)c2ccc(Cl)c(F)c2)c(=O)c1

密度：1.45 g/cm3 (Predicted)

溶解性：Soluble in DMSO ≥5mg/mL(Need ultrasonic)

纯度：≥98%

外观(性状)：White to yellow Solid

靶点活性：ERK2:0.3 nM, p-RSK:12 nM, ERK1:1.1 nM

通路：MAPK

背景说明：Ravoxertinib是一种新型的,有效的ERK1/2抑制剂。

生物活性：Ravoxertinib (GDC-0994) is an orally active ERK kinase inhibitor with an IC50 of 6.1 nM and 3.1 nM for ERK1 and ERK2， respectively.[1-3]

In Vitro：Ravoxertinib (GDC-0994) also inhibits p90RSK with an IC50 of 12 nM[1]. Ravoxertinib (GDC-0994) is highly selective for ERK1 and ERK2， with biochemical potency of 1.1 nM and 0.3 nM， respectively[2].Ravoxertinib (GDC0994; 50 nM， 0.5 μM， and 5 μM; 48 hours) decreases the viability of lung adenocarcinoma cell lines (A549， HCC827， HCC4006)[3].

In Vivo：In CD-1 mice， a 10 mg/kg oral dose of Ravoxertinib (GDC-0994) is sufficient to achieve the desired target coverage for at least 8 h[1]. Daily， oral dosing of Ravoxertinib results in significant single-agent activity in multiple in vivo cancer models， including KRAS-mutant and BRAF-mutant human xenograft tumors in mice[2].

动物实验：Mice[1] PK/PD data for Ravoxertinib (GDC-0994) in the HCT116 mouse xenograft model. HCT116 tumors are established in nude mice to a tumor volume of 400-600 mm3. Mice are treated with a single oral dose of 22 at 15， 30， or 100 mg/kg versus vehicle control alone (40% PEG400/60% (10% HPβCD)) follow by tumor and plasma collection at 2， 8， 16， and 24 h postdose. Tumor levels of phosphorylated p90RSK (pRSK) relative total p90RSK (tRSK) are measured by quantitative Western blot and are normalized to vehicle control at 2 h postdose (set to 100%). Plasma and tumor concentrations are measured by LC?MS.

储存&溶解度