VX-745


Catalog No. Size PriceQuantity
M7964-2 2mg solid $90
M7964-10 10mg solid $270

Description

VX-745, 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.

Product information

CAS Number: 209410-46-8

Molecular Weight: 436.26

Formula: C19H9Cl2F2N3OS

Synonym:

VRT-031745

VD-31745

Neflamapimod

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

Smiles: O=C1N=CN2N=C(C=CC2=C1C1C(Cl)=CC=CC=1Cl)SC1=CC=C(F)C=C1F

InChiKey: VEPKQEUBKLEPRA-UHFFFAOYSA-N

InChi: 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

Technical Data

Appearance: Solid Power

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

Solubility: DMSO: 15 mg/mL(34.38 mM). Water: Insoluble.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

VX-745 selectively inhibits p38α and p38β MAPK with IC50 of 10 nM and 220 nM, respectively, but not p38γ MAPK and a large panel of other kinases, with IC50 larger than 20 µM. In a human peripheral blood mononuclear cell (PBMC) assay, VX-745 provides IC50 of 56 and 52 nM for IL-1β and TNFα, respectively. VX-745 blocks IL-6 and IL-8 production induced by IL-1 and TNFα, and COX-2 synthesis mediated by LPS and IL-1β. [1-3] VX-745 (60 nM-20 µM) inhibits IL-6 and VEGF secretion in bone marrow stromal cells (BMSCs), without affecting their viability. VX-745 also inhibits TNF-α-induced IL-6 secretion in BMSCs. VX-745 inhibits both multiple myeloma (MM) cell proliferation and IL-6 secretion in BMSCs triggered by adherence of MM cells to BMSCs, suggesting that VX-745 can inhibit paracrine multiple myeloma (MM) cell growth in the BM milieu and overcome cell adhesion-related drug resistance. [4]

In Vivo:

VX-745 is effective against adjuvant-induced arthritis (AA) in the rat with ED50 of 5 mg/kg. Histological scores for VX-745 in AA rats are 93% inhibition of bone resorption and 56% inhibition of inflammation. In the classical cartilage-induced arthritis model, VX-745 exhibits a dose-responsive decrease in severity score. [1-3] In a type II collagen-induced arthritis (CIA) mice model, VX-745 (2.5, 5, and 10 mg/kg) has 27%, 31%, and 44% improvement in the inflammatory scores, respectively, when compared to vehicle-treated mice. In addition, histological scores show a 32-39% protection of bone and cartilage erosion by VX-745. [5]

References:

  1. Decicco C, et al. American Chemical Society, 2000, IDDB3.
  2. Haddad JJ, Curr Opin Investig Drugs, 2001, 2(8), 1070-1076.
  3. Salituro FG, et al. 27th National Medicinal Chemistry Symposium
  4. Hideshima T, et al. Blood, 2003, 101(2), 703-705.
  5. Duffy JP, et al. ACS Med Chem Lett, 2011, 2(10), 758-763.

Products are for research use only. Not for human use.

Payment & Security

American Express Diners Club Discover JCB Mastercard PayPal Venmo Visa

Your payment information is processed securely. We do not store credit card details nor have access to your credit card information.

Estimate shipping

You may also like

Recently viewed