| 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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| Other Sizes |
| Targets |
ERK5 (IC50 = 88 nM)
JWG-071 targets Extracellular Signal-Regulated Kinase 5 (ERK5/MAPK7). It also demonstrates potent activity against LRRK2. As an ATP-competitive inhibitor, it binds to the ATP-binding pocket of ERK5, inhibiting its kinase activity. The compound was designed to reduce off-target BRD4/BET inhibitory activity, a problem that plagued earlier ERK5 inhibitors. It inhibits ERK5 and LRRK2 with IC₅₀ values of 88 nM and 109 nM, respectively. |
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| ln Vitro |
JWG-071 has an IC50 of 88 and 109 nM, respectively, which inhibits ERK5 and LRRK2[1].
In vitro, JWG-071 demonstrates potent inhibition of ERK5 with an IC₅₀ of 88 nM. It shows high selectivity for ERK5 over other kinases and is designed to avoid the confounding off-target effects on the BRD4 bromodomain, a major limitation of earlier ERK5 probes. The compound's selectivity makes it a valuable tool for studying ERK5-specific biology without the interference of BET-related pathways. It also inhibits LRRK2 with an IC₅₀ of 109 nM. |
| ln Vivo |
In vivo studies have demonstrated that JWG-071 possesses good pharmacokinetic properties and is orally bioavailable. In mouse xenograft models, oral administration of the compound effectively prolonged the lifespan in MOLM13 and HL60 models. Its high oral bioavailability (84% in mice) and favorable properties make it a definitive standard for ERK5 target validation in vivo. The compound is designed for research use to study the role of ERK5 in various disease models.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for JWG-071 typically involve kinase inhibition studies using recombinant ERK5. The compound is incubated with ERK5, ATP, and a specific substrate in kinase assay buffer. Phosphorylation of the substrate is measured using either radioactive ³³P-ATP incorporation followed by filter binding and scintillation counting, or through luminescence-based assays such as ADP-Glo. IC₅₀ values are calculated from dose-response curves. Selectivity profiling is performed using a panel of kinases at a fixed compound concentration. ATP-competition assays can confirm the mechanism of action.
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| Cell Assay |
For in vitro cell-based assays, cancer cell lines are cultured and treated with JWG-071 at concentrations ranging from 0.1-10 µM for 24-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assays. ERK5 inhibition is confirmed by measuring the phosphorylation of downstream ERK5 substrates via Western blot. Cell cycle analysis is performed by propidium iodide staining and flow cytometry. Apoptosis is evaluated by Annexin V/PI staining and caspase-3/7 activity assays. The compound's selectivity over BRD4 can be confirmed by assessing c-Myc expression, which is not suppressed by JWG-071.
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| Animal Protocol |
In vivo animal studies with JWG-071 typically use mouse xenograft models. Immunodeficient mice are subcutaneously implanted with human cancer cells (e.g., MOLM13, HL60). When tumors reach a certain size, mice are treated with JWG-071 orally at doses determined from pharmacokinetic studies. Tumor volume and body weight are monitored regularly. At study endpoint, tumors are excised, weighed, and processed for histopathological and molecular analyses (e.g., immunohistochemistry for Ki-67, cleaved caspase-3). Blood samples are collected for pharmacokinetic analysis to assess compound exposure and bioavailability.
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| ADME/Pharmacokinetics |
JWG-071 is an orally bioavailable compound with high bioavailability (84% in mice). It has a molecular weight of 612.76 g/mol and is soluble in DMSO. The compound is formulated in appropriate vehicles for in vivo administration. Pharmacokinetic parameters including Cmax, Tmax, AUC, and half-life can be determined in preclinical species. The compound is typically stored as a powder at -20°C for up to 3 years and in solvent at -80°C for up to 6 months. Its favorable pharmacokinetic profile supports its use as a chemical probe for in vivo target validation.
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| Toxicity/Toxicokinetics |
In preclinical studies, JWG-071 has shown a favorable safety profile. At therapeutic doses, the compound is well-tolerated in animal models with no significant body weight loss or organ toxicity reported. The compound's high selectivity for ERK5 over other kinases, including BRD4, reduces the risk of off-target toxicities that were associated with earlier ERK5 inhibitors. Standard preclinical toxicology studies would be required for therapeutic development. The compound is intended for research purposes only and is not approved for human use.
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| References | |
| Additional Infomation |
JWG-071 is a first-in-class, kinase-selective chemical probe for ERK5. It was developed to overcome the polypharmacology of earlier ERK5 inhibitors, which also targeted the BRD4 bromodomain. The compound is a valuable tool for studying ERK5 biology in cancer and other diseases. It has a CAS number of 2250323-50-1. JWG-071 is not an FDA-approved drug and is intended for research use only. It represents the definitive standard for ERK5 target validation in preclinical studies.
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| Molecular Formula |
C34H44N8O3
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|---|---|
| Molecular Weight |
612.764966964722
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| Exact Mass |
612.35
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| Elemental Analysis |
C, 66.64; H, 7.24; N, 18.29; O, 7.83
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| CAS # |
2250323-50-1
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| Related CAS # |
2250323-50-1
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| PubChem CID |
131842089
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
45
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| Complexity |
1000
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCC(C)N1C2=CC=CC=C2C(=O)N(C3=CN=C(N=C31)NC4=C(C=C(C=C4)C(=O)N5CCC(CC5)N6CCN(CC6)C)OC)C
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| InChi Key |
ACWOMSOYIIVIRV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C34H44N8O3/c1-6-23(2)42-28-10-8-7-9-26(28)33(44)39(4)29-22-35-34(37-31(29)42)36-27-12-11-24(21-30(27)45-5)32(43)41-15-13-25(14-16-41)40-19-17-38(3)18-20-40/h7-12,21-23,25H,6,13-20H2,1-5H3,(H,35,36,37)
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| Chemical Name |
11-butan-2-yl-2-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]anilino]-5-methylpyrimido[4,5-b][1,4]benzodiazepin-6-one
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| Synonyms |
JWG-071; JWG071; JWG 071
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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: ~100 mg/mL (~163.2 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.08 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 (4.08 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: ≥ 2.5 mg/mL (4.08 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6319 mL | 8.1597 mL | 16.3193 mL | |
| 5 mM | 0.3264 mL | 1.6319 mL | 3.2639 mL | |
| 10 mM | 0.1632 mL | 0.8160 mL | 1.6319 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.
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