Neflamapimod (VX-745) is a potent, blood-brain barrier penetrant, highly selective inhibitor of p38α inhibitor with an IC₅₀ for p38α of 10 nM and for p38β of 220 nM. Neflamapimod (VX-745) possesses anti-inflammatory activity.

Neflamapimod (VX-745) exhibits PBMC IL-1β and TNFα IC₅₀ values of 45 and 51 nM, respectively. Neflamapimod is also effective in whole blood, blocking IL-1β and TNFα release with IC₅₀ values of 150 and 180 nM, respectively.
Neflamapimod shows a promising selectivity profile, with 20-fold selectivity for p38α over p38β (K_i=220 nM).
Neflamapimod (VX-745) solutions in DMSO/DMEM inhibits the IL-6 production with IC₅₀ of 15±9 nM.
Neflamapimod (VX-745; 5.0 nM) displays potent activity and 1000-fold selectivity over closely related kinases, including ERK1, JNK1-3 and MK2. Neflamapimod (10 nM-50 μM) increasingly inhibits the anisomycin-induced activity of p38α.
Neflamapimod (VX-745; 0.06 μM-20 μM) inhibits IL-6 and VEGF secretion in BMSCs. Neflamapimod can inhibit cytokine (TNF-α, IL-6, VEGF)-induced paracrine MM cell growth, survival, and drug resistance in the BM microenvironment. Neflamapimod induces modest growth inhibition of MM.1S, RPMI8226, and U266 cell lines in a dose-dependent fashion, with inhibitory concentration of 50% (IC₅₀) of 10 μM^[4].

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Neflamapimod (VX-745; 2.5, 5, and 10 mg/kg) improves the inflammatory scores in mice by 27%, 31%, and 44%, respectively. Neflamapimod (VX-745; 1.06 mg/kg) significantly decreases the inflammation score from 2.07±0.29 for the control group to 1.42±0.06.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Neflamapimod (VX-745; 2.5, 5, and 10 mg/kg) improves the inflammatory scores in mice by 27%, 31%, and 44%, respectively. Neflamapimod (VX-745; 1.06 mg/kg) significantly decreases the inflammation score from 2.07±0.29 for the control group to 1.42±0.06.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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  . Cicenas J, et al. JNK, p38, ERK, and SGK1 Inhibitors in Cancer. Cancers (Basel). 2017 Dec 21;10(1).  [Content Brief]

  . Pradal J, et al. Intra-articular bioactivity of a p38 MAPK inhibitor and development of an extended-release system. Eur J Pharm Biopharm. 2015 Jun;93:110-7.  [Content Brief]

  [4]. Alam JJ. Selective Brain-Targeted Antagonism of p38 MAPKα Reduces Hippocampal IL-1β Levels and Improves Morris Water Maze Performance in Aged Rats. J Alzheimers Dis. 2015;48(1):219-27.  [Content Brief]

  [5]. Bagley MC, et al. Rapid synthesis of VX-745: p38 MAP kinase inhibition in Werner syndrome cells. Bioorg Med Chem Lett. 2007 Sep 15;17(18):5107-10. Epub 2007 Jul 13.  [Content Brief]

  [6]. Hideshima T, et al. Targeting p38 MAPK inhibits multiple myeloma cell growth in the bone marrow milieu. Blood, 2003, 101(2), 703-705.  [Content Brief]