| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
ERK2 (IC50 = 3.1 nM); ERK1 (IC50 = 6.1 nM); p-RSK (IC50 = 12 nM)
ERK1/2 (extracellular signal-regulated kinase 1 and 2). |
|---|---|
| ln Vitro |
Ravoxertinib also inhibits p90RSK with IC50 of 12 nM[1].
Ravoxertinib has a biochemical potency of 1.1 nM and 0.3 nM, respectively, and is highly selective for ERK1 and ERK2[2]. Ravoxertinib (GDC0994; 50 nM, 0.5 µM, and 5 µM; 48 hours) reduces the viability of lung adenocarcinoma cell lines (A549, HCC827, and HCC4006)[4]. Ravoxertinib is an orally bioavailable and selective inhibitor of ERK kinase activity. It has IC50 values of 6.1 nM and 3.1 nM for ERK1 and ERK2, respectively. The compound's in vitro activity is characterized by its ability to inhibit ERK1/2 kinase activity, thereby blocking downstream signaling pathways involved in cell proliferation and survival. |
| ln Vivo |
To achieve the desired target coverage for at least 8 hours in CD-1 mice, a 10 mg/kg oral dose of Ravoxertinib is sufficient[1]. In numerous in vivo cancer models, such as KRAS- and BRAF-mutant human xenograft tumors in mice, daily oral dosing of ravoxertinib produces significant single-agent activity[2].
Ravoxertinib is being developed as an anticancer drug. Specific in vivo activity data is not detailed in the available literature. Based on its mechanism of action as an ERK1/2 inhibitor, it is expected to demonstrate antitumor activity in preclinical models of cancers with aberrant MAPK pathway activation, such as BRAF- or RAS-mutant tumors. |
| Enzyme 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. With an IC50 of 12 nM, ravoxertinib (GDC-0994) also inhibits p90RSK. Ravoxertinib (GDC-0994) has a biochemical potency of 1.1 nM and 0.3 nM for ERK1 and ERK2, respectively.
In vitro kinase inhibition assays using purified ERK1 or ERK2 enzymes and a peptide substrate to determine IC50 values for inhibition of kinase activity. The assay measures the incorporation of radioactive phosphate into the substrate. Selectivity profiling is conducted against a panel of kinases to determine specificity. |
| Cell Assay |
GDC-0994 potently inhibits phospho-p90RSK in tumor cells.
Cell-based assays are conducted to evaluate ERK1/2 inhibition in cancer cells. Cells are treated with Ravoxertinib, and the phosphorylation of ERK1/2 and downstream signaling molecules (such as RSK) is assessed by Western blot. Cell proliferation and survival assays are performed to evaluate the functional effects of ERK1/2 inhibition. |
| Animal Protocol |
Mice: Ravoxertinib PK/PD data in the HCT116 mouse xenograft model. In nude mice, HCT116 tumors grow to a tumor volume of 400–600 mm3. When compared to the vehicle control alone (40% PEG400/60% (10% HPβCD)), mice are given a single oral dose of 22 at 15, 30, or 100 mg/kg. Tumor and plasma samples are then collected at 2, 8, 16, and 24 hours after the dose. By using a quantitative Western blot, tumor levels of phosphorylated p90RSK (pRSK) and relative total p90RSK (tRSK) are determined. At 2 hours after the dose, these levels are normalized to the vehicle control (set to 100%). By using LC-MS, concentrations in plasma and tumors are measured.
In vivo efficacy is evaluated in animal models of cancer, such as mouse xenograft models using human tumor cell lines with MAPK pathway activation. Ravoxertinib is administered orally, and endpoints include tumor growth inhibition, pharmacodynamic markers (phospho-ERK levels), and survival. The compound's ability to inhibit tumor growth is assessed. |
| References |
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| Molecular Formula |
C21H19CL2FN6O2
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|---|---|---|
| Molecular Weight |
477.3190
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| Exact Mass |
476.093
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| CAS # |
2070009-58-2
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| Related CAS # |
Ravoxertinib;1453848-26-4
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| PubChem CID |
92044395
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| Appearance |
Light yellow to yellow solid powder
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| tPSA |
96.2
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
32
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| Complexity |
709
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1C([H])=C([H])C(=C([H])C=1F)[C@@]([H])(C([H])([H])O[H])N1C([H])=C([H])C(C2C([H])=C([H])N=C(N([H])C3=C([H])C([H])=NN3C([H])([H])[H])N=2)=C([H])C1=O.Cl[H]
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| InChi Key |
RMNVBUVHPAETTJ-GMUIIQOCSA-N
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| InChi Code |
InChI=1S/C21H18ClFN6O2.ClH/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);1H/t18-;/m1./s1
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| Chemical Name |
1-[(1S)-1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl]-4-[2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]pyridin-2-one;hydrochloride
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.24 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 30mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0950 mL | 10.4752 mL | 20.9503 mL | |
| 5 mM | 0.4190 mL | 2.0950 mL | 4.1901 mL | |
| 10 mM | 0.2095 mL | 1.0475 mL | 2.0950 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 UV traces from incubation of6with hepatocytes att= 3 h (M3 = compound7): h = human, m = mouse, r = rat, d = dog, c = cynomolgus monkey.
Compound exposure vs time in a multidose mouse PK study with compound22, formulated in 40% PEG400/60% (10% HPβCD) water.J Med Chem.2016 Jun 23;59(12):5650-60. |
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 Crystal structures of22bound to ERK2 (brown) and CDK2 (purple): (A) compound22bound to ERK2; (B) superposition of ERK2 and CDK2 cocrystal structures with compound22. Red dotted lines indicate hydrogen bonds. Red spheres indicate water molecules.
HCT116 study PK/PD analysis with compound22: PK/PD data for22in the HCT116 mouse xenograft model.J Med Chem.2016 Jun 23;59(12):5650-60. |
 Activity of22against 279 kinases at 1 μM. Illustration reproduced courtesy of Cell Signaling Technology.
HCT116 mouse xenograft data with compound22.J Med Chem.2016 Jun 23;59(12):5650-60. |
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