| Size | Price | Stock | Qty |
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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%
Ulixertinib (formerly also known as BVD-523 and VRT752271) is an ERK1/ERK2 inhibitor with a novel, potent, orally bioactive, highly selective, ATP-competitive, and reversible mechanism of action and an IC50 of <0.3 nM for ERK2. Human myeloma cells are unable to secrete VEGF, and myeloma-induced angiogenesis is also prevented by downregulating ERK protein kinase activity. By inhibiting both ERK 1 and 2 after oral administration, BVD-523 stops the activation of ERK-mediated signal transduction pathways.
| Targets |
ERK1; ERK2 (IC50 <0.3 nM)
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| ln Vitro |
Ulixertinib decreases phosphorylated ERK2 (pERK) and phosphorylation of the downstream kinase RSK (pRSK) in the A375 melanoma cell line, which has the b-RAFV600E mutation, with IC50 values of 4.1/0.14 μM, respectively. With an IC50 of 180 nM, ulixertinib also prevents A375 cell proliferation.
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| ln Vivo |
In the pharmacokinetic study, it was discovered that the assay's sensitivity and specificity were adequate for accurately describing the plasma pharmacokinetics of ulixertinib (VRT752271) in Balb/C mice.
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| Enzyme Assay |
MEK U911-activated ERK2 protein is expressed and purified in-house. Enzyme and substrate solutions are prepared in assay buffer, which is composed of 50 mM Tris (pH 7.5), 10 mM MgCl2, 0.1 mM EGTA, 10 mM DTT, and 0.01% (v/v) CHAPS. A polypropylene, 384-well plate with test and reference control substances is filled with 10 µL of 1.2 nM ERK2 protein that has been prepared in assay buffer. In order to determine the compound IC50s, the compound plates had previously been dosed with a 12-point range from 100 µM down to 0.1 nM, with a total DMSO concentration in the assay of 1%. Following a 20-minute pre-incubation period at room temperature, 10 µL of substrate solution—consisting of 16 µM erktide (IPTTPITTTYFFFK) and 120 µM ATP (measured Km) in assay buffer—is added. The addition of 80 µl of 1% (v/v) formic acid quenches the reaction after it has been allowed to proceed for 20 minutes at room temperature. The RapidFire Mass Spectrometry platform is then used to run the assay plates in order to measure the substrate (unphosphorylated Erktide) and product (phosphorylated Erktide) levels.
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| Cell Assay |
A375 cells are cultured in cell media composed of DMEM, 10% (v/v) Foetal Calf Serum and 1% (v/v) L-Glutamine. Cells are harvested, dispensed into black 384-well Costar plates with 200 cells per well and a total volume of 40 L cell media, and then incubated overnight at 37°C, 90% relative humidity, and 5% CO2 in a rotating incubator. Using a Labcyte Echo 555 acoustic dispenser, test substances and reference controls are directly dosed into the inner 308 wells of the cell plates. With a total DMSO concentration in the assay of 0.3%, the cells are dosed over a 12 point range from 30 M down to 0.03 nM in order to determine the compound IC50s. Following that, the cell plates are incubated for 72 hours at 37°C. In order to fix and stain the cells, 20 µL of 12% formaldehyde was added to PBS/A (4% final concentration) along with a 1:2000 dilution of Hoechst 33342. The cells were then incubated for 30 minutes at room temperature before being washed with PBS/A. A Cellomics ArrayScanTM VTI imaging platform is used to count the cells on the stained cell plates. Additionally, a Day 0 cell plate is fixed, stained, and read to produce a baseline cell count for assessing both the anti-proliferative and cytotoxic effects of the compound.
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| Animal Protocol |
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| References |
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| Molecular Formula |
C21H23CL3N4O2
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|---|---|
| Molecular Weight |
469.791
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| Elemental Analysis |
C, 53.69; H, 4.93; Cl, 22.64; N, 11.93; O, 6.81
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| CAS # |
1956366-10-1
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| Related CAS # |
Ulixertinib;869886-67-9
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| Appearance |
White to off-white solid powder
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| SMILES |
CC(C)NC1=NC=C(C(=C1)C2=CNC(=C2)C(=O)N[C@H](CO)C3=CC(=CC=C3)Cl)Cl.Cl
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| InChi Key |
DKGYQCPFBWFTHM-FSRHSHDFSA-N
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| InChi Code |
InChI=1S/C21H22Cl2N4O2.ClH/c1-12(2)26-20-8-16(17(23)10-25-20)14-7-18(24-9-14)21(29)27-19(11-28)13-4-3-5-15(22)6-13;/h3-10,12,19,24,28H,11H2,1-2H3,(H,25,26)(H,27,29);1H/t19-;/m1./s1
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| Chemical Name |
N-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-4-[5-chloro-2-(propan-2-ylamino)pyridin-4-yl]-1H-pyrrole-2-carboxamide;hydrochloride
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| Synonyms |
BVD-523; VRT752271BVD-523; BVD 523; BVD523; VRT752271; VRT752271; VRT 752271; Ulixertinib
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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) |
DMSO: 86~100 mg/mL (198.5~212.9 mM)
Ethanol: ~86 mg/mL (~198.5 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.43 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 20.8 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: ≥ 2.08 mg/mL (4.43 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 20.8 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: ≥ 2.08 mg/mL (4.43 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 5%DMSO+40%PEG300+5%Tween80+50%ddH2O: 4.3mg/ml |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1286 mL | 10.6431 mL | 21.2861 mL | |
| 5 mM | 0.4257 mL | 2.1286 mL | 4.2572 mL | |
| 10 mM | 0.2129 mL | 1.0643 mL | 2.1286 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02608229 | Terminated | Drug: BVD-523 Drug: Gemcitabine |
Pancreatic Cancer Pancreas Cancer |
Washington University School of Medicine |
June 6, 2016 | Phase 1 |
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