p38 Mitogen-activated Protein (MAP) Kinase Focused Library

Inflammatory and neuropathic pain are usually caused by tissue inflammation and nerve injury, respectively, in which multiple inflammatory cytokines and other active molecules activate different signaling pathways involved in the development and/or maintenance of pain. P38 mitogen-activated protein kinase (p38 MAPK), the most important member of the MAPK family controlling the inflammatory response, is isolated and purified by being stimulated with endotoxin in mammalian cells using a tyrosine. P38 MAPK is activated in neurons and glial cells and contributes significantly to both inflammation and neuropathic pain. It can also be activated by physiological stress, lipopolysaccharide, osmotic stress and UV irradiation. The p38 pathway may act both upstream and downstream of caspases during apoptosis, so the p38 signaling pathway is involved in both cell proliferation, differentiation, and apoptosis. P38 MAP kinase inhibitors are effective in several disease models including inflammatory arthritis and other joint diseases, and treatment with p38 MAP kinase inhibitors attenuates p38 activation and disease severity. Therefore, scientists have extensively tested structurally diverse p38 MAP kinase inhibitors in preclinical studies to provide new targets for pain treatment.

BOC Sciences is committed to establishing a p38 MAP kinase focused library to offer structurally diverse MAP kinase inhibitors.

Figure 1. A diagram of the p38 pathway. (Han, J.; et al. 2020)

Library Design

BOC Sciences’ p38 MAP focused library is built for identifying type I inhibitors that bind to the ATP-binding site of proteins within DFG-in conformation of the activation loop.

1. Firstly, our scientists have comprehensively studied the X-ray crystal structures of the target enzymes in complex with the inhibitors to investigate the kinase selectivity of these inhibitors
2. A pre-selected docking of entire BOC Sciences compound collection is performed by employing the Rule of Five and Veber rules
3. Then, we use the p38 MAPK structure recorded in the PDB entry for docking studies in which docking program is designed to perform molecular docking and results analysis
4. BOC Sciences supports GROMACS software to conduct the molecular dynamics (MD) simulations and protein structure preparation
• The ligand molecules are processed with GAMESS and GROMACS
• The main features and constraints of the docking procedure are determined from the following key residues of the protein binding pocket:
  1）Donor/acceptor sites: Met109, Glu110, Asp168, Glu71, Lys53
  2）Responsible for hydrophobic interactions: Thr106, Phe169, Leu74, Leu75, Val30, Leu171, Leu108
5. Finally, the entire BOC Sciences compound collection is processed using multiple in-house filters to detect and remove PANS compounds

Figure 2. Substrates of p38 group members -kinases. (Han, J.; et al. 2020)

p38 Mitogen-activated Protein (MAP) Kinase Focused Library Characteristics

• Favorable physicochemical parameters and solubility requirements
• No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
• Bioactivity and safety confirmed by preclinical studies and clinical trials
• Structural diversity, medicinal activity, and cellular penetration
• Structural document, IC₅₀, and other chemical and biological data are provided
• All compounds are continually updated
• Compound cherry-picking service is provided

What We Deliver

• Delivered within 2 weeks in any customer-preferred format
• Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
• All compounds have a minimum purity of 90% assessed by ¹H NMR and HPLC
• Analytical data is provided

BOC Sciences provides professional, rapid and high-quality services of p38 Mitogen-activated Protein (MAP) Kinase Focused Library design at competitive prices for global customers. Personalized and customized services of p38 Mitogen-activated Protein (MAP) Kinase Focused Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!