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2mg |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Purity: ≥98%
SCH772984 (SCH-772984) is a novel, potent and ATP-competitive inhibitor of ERK1/2 with potential antitumor activity. In a cell-free assay, it inhibits ERK1/2 with IC50 values of 4 nM and 1 nM, respectively. An affinity-based mass spectrometry high-throughput platform with potential anticancer activity found SCH772984. Out of the 300 kinases tested, SCH772984 is highly selective against them, causing more than 50% inhibition at a concentration of 1 μmol/L for kinases like CLK2, FLT4, GSG2, MAP4K4, MAPK1, MINK1, PRKD1, and TTK.
Targets |
ERK2 (IC50 = 1 nM); ERK1 (IC50 = 4 nM)
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ln Vitro |
SCH772984 is a novel, selective and ATP competitive inhibitor of ERK1/2. The phosphorylation of p90 ribosomal S6 kinase, an ERK substrate, is inhibited by SCH772984 in a dose-dependent manner (T359/S363 phospho-RSK). Additionally, phosphorylation of ERK's own activation loop residues is inhibited by SCH772984. SCH772984 exhibits EC50 values <500 nM in approximately 88% and 49% of BRAF-mutant or RAS-mutant tumor lines, respectively. Importantly, SCH772984 successfully inhibited MAPK signaling and cell proliferation in tumor cells that were resistant to concurrent treatment with BRAF and MEK inhibitors. [1]
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ln Vivo |
SCH772984 induces tumor regressions in xenograft models at tolerated doses. In models with resistance to BRAF or MEK inhibitors, SCH772984 successfully inhibits MAPK signaling and cell proliferation. [1]
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Enzyme Assay |
SCH772984 is tested in 8 point dilution curves in duplicate against purified ERK2 or ERK1. The reaction plate is filled with the enzyme. and then a substrate peptide and ATP solution were added after the compound had been incubated. Each well of a 384-well plate receives 14 μl of diluted enzyme (0.3ng active ERK2 per reaction). The reagents are carefully mixed in the plates before they are incubated for 45 minutes at room temperature. With 60 l of IMAP Binding Solution (1:2200 dilutions of IMAP beads in 1X Binding Buffer), the reaction is stopped. To ensure complete binding of phosphopeptides to the IMAP beads, the plates are incubated for an additional 0.5 hours at room temperature. On the LJL Analyst, plates are read.
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Cell Assay |
Cells are plated at a density of 4,000 per well for 96-well cell proliferation experiments (six replicates). Cells are treated with DMSO or 9 point IC50 dilution (0.001-10 μM) at 1% DMSO final for all concentrations 24 hours after cell seeding. Viability is assessed using a ViaLight luminescence kit five days after dosing, as per the manufacturer's instructions. CellTiterGlo luminescent cell viability assay is used to measure the viability of cell lines after they have been treated with SCH772984 for 4 days.
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Animal Protocol |
Nude mice
12.5 mg/kg, 25 mg/kg, 50 mg/kg i.p. |
References |
Molecular Formula |
C33H33N9O2
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Molecular Weight |
587.67
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Exact Mass |
587.28
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Elemental Analysis |
C, 67.44; H, 5.66; N, 21.45; O, 5.44
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CAS # |
942183-80-4
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Related CAS # |
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Appearance |
Yellow Solid powder
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SMILES |
C1CN(C[C@@H]1C(=O)NC2=CC3=C(C=C2)NN=C3C4=CC=NC=C4)CC(=O)N5CCN(CC5)C6=CC=C(C=C6)C7=NC=CC=N7
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InChi Key |
HDAJDNHIBCDLQF-RUZDIDTESA-N
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InChi Code |
InChI=1S/C33H33N9O2/c43-30(42-18-16-41(17-19-42)27-5-2-24(3-6-27)32-35-11-1-12-36-32)22-40-15-10-25(21-40)33(44)37-26-4-7-29-28(20-26)31(39-38-29)23-8-13-34-14-9-23/h1-9,11-14,20,25H,10,15-19,21-22H2,(H,37,44)(H,38,39)/t25-/m1/s1
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Chemical Name |
(3R)-1-[2-oxo-2-[4-(4-pyrimidin-2-ylphenyl)piperazin-1-yl]ethyl]-N-(3-pyridin-4-yl-1H-indazol-5-yl)pyrrolidine-3-carboxamide
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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 |
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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: ≥ 2.4 mg/mL (4.08 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: ≥ 1.43 mg/mL (2.43 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 14.3 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: 1.43 mg/mL (2.43 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: ≥ 1.43 mg/mL (2.43 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 14.3 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. Solubility in Formulation 5: 5% DMSO+30% PEG 300+ddH2O: 0.6mg/mL Solubility in Formulation 6: 20 mg/mL (34.03 mM) in 20% SBE-β-CD adjusted to pH 4-4.5 with 1 N acetic (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.7016 mL | 8.5082 mL | 17.0164 mL | |
5 mM | 0.3403 mL | 1.7016 mL | 3.4033 mL | |
10 mM | 0.1702 mL | 0.8508 mL | 1.7016 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.
Biochemical and cell-based activity of SCH772984.A, chemical structure of SCH772984.B, effects of SCH772984 on kinase activity of ERK1, ERK2, and MEK1.C, SCH772984 inhibits ERK and RSK phosphorylation.D, TdF binding activity of SCH772984, VTX-11e, or GSK1120212 to recombinant ERK2 and MEK1 enzymes.Cancer Discov.2013 Jul;3(7):742-50. td> |
SCH772984 is efficacious inBRAF- orRAS-mutant tumor cells. SCH772984 is efficacious in BRAF and MEK combination resistance inBRAF-mutant A101D melanoma cells.Cancer Discov.2013 Jul;3(7):742-50. td> |
SCH772984 is efficacious in tumor cell lines refractory to either BRAF or MEK inhibitors.Cancer Discov.2013 Jul;3(7):742-50. td> |