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Purity: ≥98%
Ravoxertinib (formerly known as GDC0994; RG7842) is a novel, potent, orally bioavailable inhibitor of extracellular signal-regulated kinase (ERK1/2) with potential antineoplastic activity. It blocks ERK1/2 with IC50 values of 1.1 nM and 0.3 nM, respectively. In the clinical trial NCT01875705, ravoxertinib is being examined in patients with locally advanced or metastatic solid tumors. It exhibits both in vivo and in vitro high anti-proliferative activity.
Targets |
ERK1 (IC50 = 6.1 nM); ERK2 (IC50 = 3.1 nM); p-RSK (IC50 = 12 nM)
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ln Vitro |
Ravoxertinib (GDC-0994) also inhibits p90RSK with an IC50 of 12 nM[1].
Ravoxertinib (GDC-0994) 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)[3]. |
ln Vivo |
In CD-1 mice, a 10 mg/kg oral dose of Ravoxertinib (GDC-0994) adequate to provide the desired target coverage in CD-1 mice for at least 8 hours[1]. When given orally every day, Ravoxertinib exhibits significant single-agent activity in a number of in vivo cancer models, including KRAS- and BRAF-mutant human xenograft tumors in mice[2].
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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. Additionally, p90RSK is inhibited by ravoxertinib (GDC-0994), with an IC50 of 12 nM. With a biochemical potency of 1.1 nM and 0.3 nM, respectively, ravoxertinib (GDC-0994) is highly selective for ERK1 and ERK2.
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Cell Assay |
GDC-0994 potently inhibits phospho-p90RSK in tumor cells.
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Animal Protocol |
Mice: PK/PD data for the mouse xenograft HCT116 model of ravoxertinib (GDC-0994). In nude mice, 400–600 mm3 of tumor volume is reached by HCT116 tumors. Tumor and plasma samples are collected 2, 8, 16, and 24 hours after the initial oral dose of 22 at 15, 30, or 100 mg/kg for mice versus the vehicle control alone (40% PEG400/60% (10% HPβCD)). Quantitative Western blotting is used to assess the relative levels of total p90RSK (tRSK) and phosphorylated p90RSK (pRSK) in tumors. At 2 hours after the dose, these levels are normalized to the vehicle control (set to 100%). LC-MS is used to determine the concentrations in plasma and tumors.
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References |
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Molecular Formula |
C21H18CLFN6O2
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Molecular Weight |
439.85
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Exact Mass |
440.12
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Elemental Analysis |
C, 57.21; H, 4.12; Cl, 8.04; F, 4.31; N, 19.06; O, 7.26
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CAS # |
1453848-26-4
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Related CAS # |
Ravoxertinib hydrochloride;2070009-58-2
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Appearance |
Solid powder
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SMILES |
CN1C(=CC=N1)NC2=NC=CC(=N2)C3=CC(=O)N(C=C3)[C@H](CO)C4=CC(=C(C=C4)Cl)F
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InChi Key |
RZUOCXOYPYGSKL-GOSISDBHSA-N
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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
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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 |
RG7842; GDC-0994; RG 7842; GDC 0994; GDC0994; RG-7842
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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 |
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 (5.67 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.67 mg/mL (3.79 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 16.7 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. View More
Solubility in Formulation 3: ≥ 1.67 mg/mL (3.79 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. Solubility in Formulation 4: ≥ 1.67 mg/mL (3.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 5: 2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 30mg/mL Solubility in Formulation 6: 5 mg/mL (11.34 mM) in 30% PEG300 70% (10% HP-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.2735 mL | 11.3675 mL | 22.7350 mL | |
5 mM | 0.4547 mL | 2.2735 mL | 4.5470 mL | |
10 mM | 0.2274 mL | 1.1368 mL | 2.2735 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. td> |
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. td> |
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. td> |