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Neflamapimod (VX-745)

Name: Neflamapimod (VX-745)
Brand: Selleck Chemicals
SKU: S1458
Rating: 5 (12 reviews)

Catalog No.S1458

For research use only.

Neflamapimod (VX-745) is a potent and selective inhibitor of p38α with IC50 of 10 nM, 22-fold greater selectivity versus p38β and no inhibition to p38γ.

Neflamapimod (VX-745) Chemical Structure

CAS No. 209410-46-8

Selleck's Neflamapimod (VX-745) has been cited by 12 Publications

1 Customer Review

Purity & Quality Control

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p38 MAPK Signaling Pathway Map

Biological Activity

Description

Neflamapimod (VX-745) is a potent and selective inhibitor of p38α with IC50 of 10 nM, 22-fold greater selectivity versus p38β and no inhibition to p38γ.

Features

A potent and selective inhibitor to p38α and p38β MAPK.

Targets

p38α ^[1]	p38β ^[1]
10 nM	220 nM

In vitro

VX-745 selectively inhibits p38α and p38β MAPK with IC50 of 10 nM and 220 nM, respectively, but not p38γ MAPK and a large panel of other kinases, with IC50 larger than 20 µM. In a human peripheral blood mononuclear cell (PBMC) assay, VX-745 provides IC50 of 56 and 52 nM for IL-1β and TNFα, respectively. VX-745 blocks IL-6 and IL-8 production induced by IL-1 and TNFα, and COX-2 synthesis mediated by LPS and IL-1β. ^[1-3] VX-745 (60 nM-20 µM) inhibits IL-6 and VEGF secretion in bone marrow stromal cells (BMSCs), without affecting their viability. VX-745 also inhibits TNF-α-induced IL-6 secretion in BMSCs. VX-745 inhibits both multiple myeloma (MM) cell proliferation and IL-6 secretion in BMSCs triggered by adherence of MM cells to BMSCs, suggesting that VX-745 can inhibit paracrine multiple myeloma (MM) cell growth in the BM milieu and overcome cell adhesion-related drug resistance. ^[4]

In vivo

VX-745 is effective against adjuvant-induced arthritis (AA) in the rat with ED50 of 5 mg/kg. Histological scores for VX-745 in AA rats are 93% inhibition of bone resorption and 56% inhibition of inflammation. In the classical cartilage-induced arthritis model, VX-745 exhibits a dose-responsive decrease in severity score. ^[1-3] In a type II collagen-induced arthritis (CIA) mice model, VX-745 (2.5, 5, and 10 mg/kg) has 27%, 31%, and 44% improvement in the inflammatory scores, respectively, when compared to vehicle-treated mice. In addition, histological scores show a 32-39% protection of bone and cartilage erosion by VX-745. ^[5]

Protocol (from reference)

Kinase Assay:^[5]	Spectrophotometric coupled-enzyme assay: The IC50 for the inhibition of p38α and p38β homologs are obtained by a spectrophotometric coupled-enzyme assay. A fixed concentration of enzyme (15 nM of p38α or p38β) is incubated with VX-745 in DMSO for 10 min. at 30 °C in 0.1 M HEPES buffer, pH 7.5, containing 10% glycerol, 10 mM MgCl₂, 2.5 mM phosphoenolpyruvate, 200 µM NADH, 150 µg/mL pyruvate kinase, 50 µg/mL lactate dehydrogenase, and 200 µM EGF receptor peptide (KRELVEPLTPSGEAPNQALLR). The reaction is initiated with 100 µM and 70 µM ATP for p38α and p38β assays, respectively. The decrease of absorbance at 340 nm is monitored to follow the rate of the reaction. IC50 is evaluated from the rate data as a function of the inhibitor concentration.
Cell Research:^[4]	Cell lines: Human bone marrow stromal cells (BMSCs) and multiple myeloma (MM) cells Concentrations: 60 nM - 20 μM, dissolved in DMSO. Incubation Time: 48 hours Method: BMSCs (5 × 10⁴ cells/well) or MM cells (3 × 10⁴ cells/well) are incubated in 96-well culture plates in the presence or absence of VX-745 for 48 hours at 37 °C. DNA synthesis is measured by [³H]-thymidine ([³H]TdR) uptake. Cells are pulsed with [³H]TdR (0.5 μCi/well [.0185 MBq]) during the last 8 hours of 48-hour cultures. Growth inhibition of both MM cells and BMSCs by VX-745 is also assessed by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) dye absorbance.
Animal Research:^[5]	Animal Models: Type II collagen-induced arthritis (CIA) mice model (DBA/1J) Dosages: 2.5, 5, and 10 mg/kg Administration: Oral gavage twice daily

References

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Solubility (25°C)

In vitro


In vivo	Add solvents to the product individually and in order (Data is from Selleck tests instead of citations): 30% PEG400+0.5% Tween80+5% propylene glycol For best results, use promptly after mixing. Click to purchase: PEG400 Tween 80	30 mg/mL

Chemical Information

Molecular Weight	436.26
Formula	C₁₉H₉Cl₂F₂N₃OS
CAS No.	209410-46-8
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	C1=CC(=C(C(=C1)Cl)C2=C3C=CC(=NN3C=NC2=O)SC4=C(C=C(C=C4)F)F)Cl

Download Neflamapimod (VX-745) SDF

In vivo Formulation Calculator (Clear solution)

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Molarity Calculator

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Clinical Trial Information

NCT Number	Recruitment	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT02423200	Completed	Drug: VX-745	Alzheimer''s Disease	EIP Pharma Inc	April 2015	Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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