Doramapimod

• CAT Number: I002974
• CAS Number: 285983-48-4
• Molecular Formula: C₃₁H₃₇N₅O₃
• Molecular Weight: 527.66
• Purity: ≥95%
• Target: p38
• Solubility: DMSO ≥102 mg/mL Water <1.2 mg/mL Ethanol ≥ 102mg/mL
• Storage: -20°C
• IC50: 0.1 nM (Kd)
• IUPAC Name: 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea
• InChI: InChI=1S/C31H37N5O3/c1-22-9-11-23(12-10-22)36-29(21-28(34-36)31(2,3)4)33-30(37)32-26-13-14-27(25-8-6-5-7-24(25)26)39-20-17-35-15-18-38-19-16-35/h5-14,21H,15-20H2,1-4H3,(H2,32,33,37)
• InChIKey: MVCOAUNKQVWQHZ-UHFFFAOYSA-N
• SMILES: CC1=CC=C(C=C1)N2C(=CC(=N2)C(C)(C)C)NC(=O)NC3=CC=C(C4=CC=CC=C43)OCCN5CCOCC5

Doramapimod (Cat No.:I002974) is a pan-p38 MAPK inhibitor with IC50 of 38 nM, 65 nM, 200 nM, and 520 nM for p38α/β/γ/δ in cell-free assays, respectively, and can interact with p38α binding, Kd is 0.1 nM in THP-1 cells, 330-fold more selective than JNK2, weaker inhibitory effect on c-RAF, Fyn and Lck, weaker inhibitory effect on ERK-1, SYK, IKK2 effect.

Reference

1:J Pharmacol Sci. 2015 Nov;129(3):135-42. doi: 10.1016/j.jphs.2015.06.008. Epub 2015 Jul 3. In vitro anti-osteoclastogenic activity of p38 inhibitor doramapimod via inhibiting migration of pre-osteoclasts and NFATc1 activity.Moon SH,Choi SW,Kim SH, PMID: 26232862 DOI: 10.1016/j.jphs.2015.06.008 Abstract: The mitogen activated protein kinase p38 plays a role in the receptor activator of NF-ĸB ligand (RANKL)-induced osteoclast differentiation. In this study, we investigated the effect of p38 inhibitor doramapimod on the osteoclast differentiation. Doramapimod significantly inhibited the osteoclastogenesis of bone marrow macrophages (BMMs) via attenuating the activation of p38 induced by M-CSF and RANKL. Importantly, doramapimod blocked the migration and fusion in pre-osteoclasts via the down-regulating NFATc1. The inhibitory effect of doramapimod on the migration/fusion of pre-osteoclasts via inhibiting NFATc1 activity were confirmed by measuring NFATc1 luciferase activity and evaluating the mRNA expression of NFATc1-responsive genes related to the osteoclastic migration/fusion. These results suggested anti-osteoclastogenic activity of doramapimod via inhibiting migration/fusion of pre-osteoclasts and NFATc1 activity. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.