| CAS |
No.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 |
| 溶解性 |
Soluble in DMSO ≥5mg/mL(Need ultrasonic) |
| 纯度 |
≥98% |
| 外观(性状) |
White to yellow Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD28143918 |
| SMILES |
O=C1C=C(C2=NC(NC3=CC=NN3C)=NC=C2)C=CN1[C@@H](C4=CC=C(Cl)C(F)=C4)CO |
| 靶点 |
ERK |
| 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. |
| 数据来源文献 |
[1]. Blake JF， et al. Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994)， an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Developme
[2]. Kirk Robarge， et al. Abstract DDT02-03: Discovery of GDC-0994， a potent and selective ERK1/2 inhibitor in early clinical development. Proceedings: AACR Annual Meeting 2014; April 5-9， 2014.
[3]. MICHAEL LAI. Opportunity for Pharmaceutical Intervention in Lung Cancer: Selective Inhibition of JAK1/2 to Eliminate EMT-Derived Mesenchymal Cells. |
| 规格 |
2mg 5mg 10mg 25mg 50mg |
| 单位 |
瓶 |
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