| CAS NO: | 1453848-26-4 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 5mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 250mg | 电议 |
| 500mg | 电议 |
| Molecular Weight (MW) | 439.85 |
|---|---|
| Formula | C21H18ClFN6O2 |
| CAS No. | 1453848-26-4 |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Solubility (In vitro) | DMSO: 87 mg/mL (197.8 mM) |
| Water: <1 mg/mL | |
| Ethanol: 87 mg/mL (197.8 mM) | |
| Solubility (In vivo) | 2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 30 mg/mL |
| Synonyms | RG7842; GDC-0994; RG 7842; GDC 0994; GDC0994;RG-7842; Chemical Name: (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 InChi Key: RZUOCXOYPYGSKL-GOSISDBHSA-N InChi Code: InChI=1S/C21H18ClFN6O2/c1-28-19(5-8-25-28)27-21-24-7-4-17(26-21)13-6-9-29(20(31)11-13)18(12-30)14-2-3-15(22)16(23)10-14/h2-11,18,30H,12H2,1H3,(H,24,26,27)/t18-/m1/s1 SMILES Code: O=C1C=C(C2=NC(NC3=CC=NN3C)=NC=C2)C=CN1[C@@H](C4=CC=C(Cl)C(F)=C4)CO |
| In Vitro | In vitro activity: GDC-0994, also known as ravoxertinib and RG7842, is a potent, orally available ERK1/2 inhibitor with IC50 of 1.1 nM and 0.3 nM, respectively. It has demonstrated anticancer activity. Upon oral administration, GDC-0994 inhibits both ERK phosphorylation and activation of ERK-mediated signal transduction pathways. This prevents ERK-dependent tumor cell proliferation and survival. Kinase Assay: Ravoxertinib (GDC-0994) is an orally bioavailable ERK kinase inhibitor with an IC50 of 6.1 nM and 3.1 nM for ERK1 and ERK2, respectively. Ravoxertinib (GDC-0994) also inhibits p90RSK with an IC50 of 12 nM. Ravoxertinib (GDC-0994) is highly selective for ERK1 and ERK2, with biochemical potency of 1.1 nM and 0.3 nM, respectively. Cell Assay: GDC-0994 potently inhibits phospho-p90RSK in tumor cells. |
|---|---|
| In Vivo | GDC-0994 (p.o.) results in significant single-agent activity in multiple in vivo cancer models, including KRAS-mutant and BRAF-mutant human xenograft tumors in mice. In vivo, GDC-0994 (p.o.) inhibits both ERK phosphorylation and activation of ERK-mediated signal transduction pathways, and subsequently prevents ERK-dependent tumor cell proliferation and survival. |
| Animal model | 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. |
| Formulation & Dosage | Dissolved in 40% PEG400/60% (10% HPβCD); 15, 30, or 100 mg/kg; oral |
| References | J Med Chem. 2016 Jun 23;59(12):5650-60. |
UV traces from incubation of 6 with hepatocytes at t = 3 h (M3 = compound 7): h = human, m = mouse, r = rat, d = dog, c = cynomolgus monkey.
Compound exposure vs time in a multidose mouse PK study with compound 22, formulated in 40% PEG400/60% (10% HPβCD) water. J Med Chem. 2016 Jun 23;59(12):5650-60. |
Crystal structures of 22 bound to ERK2 (brown) and CDK2 (purple): (A) compound 22 bound to ERK2; (B) superposition of ERK2 and CDK2 cocrystal structures with compound 22. Red dotted lines indicate hydrogen bonds. Red spheres indicate water molecules.
HCT116 study PK/PD analysis with compound 22: PK/PD data for 22 in the HCT116 mouse xenograft model. J Med Chem. 2016 Jun 23;59(12):5650-60. |
Activity of 22 against 279 kinases at 1 μM. Illustration reproduced courtesy of Cell Signaling Technology.
HCT116 mouse xenograft data with compound 22. J Med Chem. 2016 Jun 23;59(12):5650-60. |
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