Neflamapimod

SKU: orb1301083

Description

Neflamapimod (VX-745) is a potent and selective p38α MAPK inhibitor with an IC50 of 10 nM, demonstrating 22-fold selectivity over p38β and no activity against p38γ. It has been utilized in preclinical research to investigate p38α's role in neuroinflammation and synaptic dysfunction, with studies conducted in both cellular and animal models of neurodegenerative diseases.

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 209410-46-8
• MW: 436.26
• Purity: 99.02%
• Formula: C₁₉H₉Cl₂F₂N₃OS
• SMILES: Fc1ccc(Sc2ccc3c(-c4c(Cl)cccc4Cl)c(=O)ncn3n2)c(F)c1
• Target: p38 MAPK,Autophagy
• Solubility: DMSO:43.6 mg/mL (99.94 mM)

Bioactivity

• Target IC50:
  p38β:220 nM|p38α:10 nM
• In Vivo:
  Neflamapimod is effective against adjuvant-induced arthritis (AA) in the rat with ED50 of 5 mg/kg. Histological scores for Neflamapimod in AA rats are 93% inhibition of bone resorption and 56% inhibition of inflammation. In the classical cartilage-induced arthritis model, Neflamapimod exhibits a dose-responsive decrease in severity score. [1-3] In a type II collagen-induced arthritis (CIA) mice model, Neflamapimod (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 Neflamapimod.
• In Vitro:
  Neflamapimod 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, Neflamapimod provides IC50 of 56 and 52 nM for IL-1β and TNFα, respectively. Neflamapimod 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] Neflamapimod (60 nM-20 μM) inhibits IL-6 and VEGF secretion in bone marrow stromal cells (BMSCs), without affecting their viability. Neflamapimod also inhibits TNF-α-induced IL-6 secretion in BMSCs. Neflamapimod inhibits both multiple myeloma (MM) cell proliferation and IL-6 secretion in BMSCs triggered by adherence of MM cells to BMSCs, suggesting that Neflamapimod can inhibit paracrine multiple myeloma (MM) cell growth in the BM milieu and overcome cell adhesion-related drug resistance.
• Cell Research:
  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.(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Autophagy, inhibit, Inhibitor, Neflamapimod, VX745, VX-745, VX 745, p38β, p38MAPK, p38α, p38 MAPK

Compound Identifiers

PubChem CID

3038525