Neflamapimod
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 203163

CAS#: 209410-46-8

Description: Neflamapimod, also known as VX-745, VRT-031745 and VD-31745, is highly potent and selective p38α inhibitor (IC50 = 10 nM). VX-745 blocks TNFα production in LPS-stimulated HWB in vitro (IC50 = 177 nM). VX-745 displays excellent enzyme activity and selectivity, has a favorable pharmacokinetic profile, and demonstrates good in vivo activity in models of inflammation.


Price and Availability

Size
Price

10mg
USD 90
100mg
USD 450
1g
USD 2450
Size
Price

25mg
USD 150
200mg
USD 750
2g
USD 3950
Size
Price

50mg
USD 250
500mg
USD 1450
5g
USD 5850

Neflamapimod, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 203163
Name: Neflamapimod
CAS#: 209410-46-8
Chemical Formula: C19H9Cl2F2N3OS
Exact Mass: 434.98114
Molecular Weight: 436.26
Elemental Analysis: C, 52.31; H, 2.08; Cl, 16.25; F, 8.71; N, 9.63; O, 3.67; S, 7.35


Synonym: VX-745; VX 745; VX745; VRT-031745, VD-31745; Neflamapimod.

IUPAC/Chemical Name: 5-(2,6-Dichlorophenyl)-2-(2,4-difluorophenylsulfanyl)-6H-pyrimido[3,4-b]pyridazin-6-one

InChi Key: VEPKQEUBKLEPRA-UHFFFAOYSA-N

InChi Code: InChI=1S/C19H9Cl2F2N3OS/c20-11-2-1-3-12(21)17(11)18-14-5-7-16(25-26(14)9-24-19(18)27)28-15-6-4-10(22)8-13(15)23/h1-9H

SMILES Code: O=C1C(C2=C(Cl)C=CC=C2Cl)=C3C=CC(SC4=CC=C(F)C=C4F)=NN3C=N1


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

VX-745 is an antiarthritic Drugs. Its activities and application include:  Myelodysplastic Syndrome Therapy, Oncolytic Drugs, Rheumatoid Arthritis, Treatment of, treatment of musculoskeletal & connective tissue diseases, Antiinflammatory Drugs, p38 Protein Kinase.
     
   


References

1: Davis T, Brook AJ, Rokicki MJ, Bagley MC, Kipling D. Evaluating the Role of p38 MAPK in the Accelerated Cell Senescence of Werner Syndrome Fibroblasts. Pharmaceuticals (Basel). 2016 Apr 28;9(2). pii: E23. doi: 10.3390/ph9020023. PubMed PMID: 27136566.

2: 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. doi: 10.3233/JAD-150277. PubMed PMID: 26401942.

3: Pradal J, Zuluaga MF, Maudens P, Waldburger JM, Seemayer CA, Doelker E, Gabay C, Jordan O, Allémann E. Intra-articular bioactivity of a p38 MAPK inhibitor and development of an extended-release system. Eur J Pharm Biopharm. 2015 Jun;93:110-7. doi: 10.1016/j.ejpb.2015.03.017. Epub 2015 Mar 30. PubMed PMID: 25836052.

4: McGuire VA, Gray A, Monk CE, Santos SG, Lee K, Aubareda A, Crowe J, Ronkina N, Schwermann J, Batty IH, Leslie NR, Dean JL, O'Keefe SJ, Boothby M, Gaestel M, Arthur JS. Cross talk between the Akt and p38α pathways in macrophages downstream of Toll-like receptor signaling. Mol Cell Biol. 2013 Nov;33(21):4152-65. doi: 10.1128/MCB.01691-12. Epub 2013 Aug 26. PubMed PMID: 23979601; PubMed Central PMCID: PMC3811899.

5: Tsai YR, Wang YJ, Lee MR, Hsu MF, Wang JP. p38 Mitogen-activated protein kinase and extracellular signal-regulated kinase signaling pathways are not essential regulators of formyl peptide-stimulated p47(phox) activation in neutrophils. Eur J Pharmacol. 2013 Feb 15;701(1-3):96-105. doi: 10.1016/j.ejphar.2013.01.003. Epub 2013 Jan 21. PubMed PMID: 23348708.

6: Azevedo R, van Zeeland M, Raaijmakers H, Kazemier B, de Vlieg J, Oubrie A. X-ray structure of p38α bound to TAK-715: comparison with three classic inhibitors. Acta Crystallogr D Biol Crystallogr. 2012 Aug;68(Pt 8):1041-50. doi: 10.1107/S090744491201997X. Epub 2012 Jul 17. PubMed PMID: 22868770.

7: Duffy JP, Harrington EM, Salituro FG, Cochran JE, Green J, Gao H, Bemis GW, Evindar G, Galullo VP, Ford PJ, Germann UA, Wilson KP, Bellon SF, Chen G, Taslimi P, Jones P, Huang C, Pazhanisamy S, Wang YM, Murcko MA, Su MS. The Discovery of VX-745: A Novel and Selective p38α Kinase Inhibitor. ACS Med Chem Lett. 2011 Jul 28;2(10):758-63. doi: 10.1021/ml2001455. eCollection 2011 Oct 13. PubMed PMID: 24900264; PubMed Central PMCID: PMC4018046.

8: Selness SR, Boehm TL, Walker JK, Devadas B, Durley RC, Kurumbail R, Shieh H, Xing L, Hepperle M, Rucker PV, Jerome KD, Benson AG, Marrufo LD, Madsen HM, Hitchcock J, Owen TJ, Christie L, Promo MA, Hickory BS, Alvira E, Naing W, Blevis-Bal R, Devraj RV, Messing D, Schindler JF, Hirsch J, Saabye M, Bonar S, Webb E, Anderson G, Monahan JB. Design, synthesis and activity of a potent, selective series of N-aryl pyridinone inhibitors of p38 kinase. Bioorg Med Chem Lett. 2011 Jul 1;21(13):4059-65. doi: 10.1016/j.bmcl.2011.04.120. Epub 2011 May 13. PubMed PMID: 21640588.

9: Verkaar F, van der Doelen AA, Smits JF, Blankesteijn WM, Zaman GJ. Inhibition of Wnt/β-catenin signaling by p38 MAP kinase inhibitors is explained by cross-reactivity with casein kinase Iδ/ɛ. Chem Biol. 2011 Apr 22;18(4):485-94. doi: 10.1016/j.chembiol.2011.01.015. PubMed PMID: 21513885.

10: Bagley MC, Davis T, Dix MC, Fusillo V, Pigeaux M, Rokicki MJ, Kipling D. Gram-scale synthesis of the p38α MAPK-inhibitor VX-745 for preclinical studies into Werner syndrome. Future Med Chem. 2010 Sep;2(9):1417-27. doi: 10.4155/fmc.10.217. PubMed PMID: 21426137.

11: Chopra P, Kulkarni O, Gupta S, Bajpai M, Kanoje V, Banerjee M, Bansal V, Visaga S, Chatterjee M, Chaira T, Shirumalla RK, Verma AK, Dastidar SG, Sharma G, Ray A. Pharmacological profile of AW-814141, a novel, potent, selective and orally active inhibitor of p38 MAP kinase. Int Immunopharmacol. 2010 Apr;10(4):467-73. doi: 10.1016/j.intimp.2010.01.007. Epub 2010 Jan 20. PubMed PMID: 20093202.

12: Bagley MC, Davis T, Dix MC, Fusillo V, Pigeaux M, Rokicki MJ, Kipling D. Microwave-assisted Ullmann C-S bond formation: synthesis of the P38alpha MAPK clinical candidate VX-745. J Org Chem. 2009 Nov 6;74(21):8336-42. doi: 10.1021/jo9017155. PubMed PMID: 19778055.

13: Genovese MC. Inhibition of p38: has the fat lady sung? Arthritis Rheum. 2009 Feb;60(2):317-20. doi: 10.1002/art.24264. PubMed PMID: 19180514.

14: Brown KK, Heitmeyer SA, Hookfin EB, Hsieh L, Buchalova M, Taiwo YO, Janusz MJ. P38 MAP kinase inhibitors as potential therapeutics for the treatment of joint degeneration and pain associated with osteoarthritis. J Inflamm (Lond). 2008 Dec 4;5:22. doi: 10.1186/1476-9255-5-22. PubMed PMID: 19055838; PubMed Central PMCID: PMC2612656.

15: Chen MH, Fitzgerald P, Singh SB, O'Neill EA, Schwartz CD, Thompson CM, O'Keefe SJ, Zaller DM, Doherty JB. Synthesis and biological activity of quinolinone and dihydroquinolinone p38 MAP kinase inhibitors. Bioorg Med Chem Lett. 2008 Mar 15;18(6):2222-6. doi: 10.1016/j.bmcl.2006.10.097. Epub 2006 Nov 6. PubMed PMID: 18316187.

16: Bagley MC, Davis T, Dix MC, Rokicki MJ, Kipling D. 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. PubMed PMID: 17659871.

17: Natarajan SR, Wisnoski DD, Thompson JE, O'Neill EA, O'Keefe SJ. p38 MAP kinase inhibitors. Part 3: SAR on 3,4-dihydropyrimido[4,5-d]pyrimidin-2-ones and 3,4-dihydropyrido[4,3-d]pyrimidin-2-ones. Bioorg Med Chem Lett. 2006 Aug 15;16(16):4400-4. Epub 2006 Jun 5. PubMed PMID: 16750629.

18: Wagner G, Laufer S. Small molecular anti-cytokine agents. Med Res Rev. 2006 Jan;26(1):1-62. Review. PubMed PMID: 16283677.

19: Natarajan SR, Doherty JB. P38 MAP kinase inhibitors: evolution of imidazole-based and pyrido-pyrimidin-2-one lead classes. Curr Top Med Chem. 2005;5(10):987-1003. Review. PubMed PMID: 16178742.

20: Foster ML, Halley F, Souness JE. Potential of p38 inhibitors in the treatment of rheumatoid arthritis. Drug News Perspect. 2000 Oct;13(8):488-97. PubMed PMID: 12937622.