VX-745

Cas No.:	209410-46-8
Chemical Name:	5-(2,6-dichlorophenyl)-2-(2,4-difluorophenylthio)-6H-pyrimido[1,6-b]pyridazin-6-one
Synonyms:	VX 745,VX745
SMILES:	O=C1N=CN(C(C=C2)=C1C3=C(Cl)C=CC=C3Cl)N=C2SC4=CC=C(F)C=C4F
Formula:	C19H9Cl2F2N3Os
M.Wt:	436.26
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Neflamapimod (VX-745) is a potent and selective inhibitor of p38α, and possesses anti-inflammatory activity.
In Vivo:	Neflamapimod (VX-745; 2.5, 5, and 10 mg/kg) improves the inflammatory scores in mice by 27%, 31%, and 44%, respectively[1]. 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[2].
In Vitro:	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 (Ki=220 nM)[1]. Neflamapimod (VX-745) solutions in DMSO/DMEM inhibits the IL-6 production with IC50 of 15±9 nM[2]. 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[3]. 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].