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• 產(chǎn)品描述： Neflamapimod (VX-745)是一種有效的，選擇性p38α抑制劑，IC50為10 nM，比作用于p38β選擇性高22倍，對(duì)p38γ沒(méi)有抑制作用

• 靶點(diǎn)： p38α:10 nM; p38β:220 nM;p38MAPK;Autophagy

• 體外研究：
  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.

• 體內(nèi)研究：
  VX-745有效治療鼠的佐劑性關(guān)節(jié)炎，ED50為5 mg/kg。VX-745作用于佐劑性關(guān)節(jié)炎鼠，抑制骨重吸收達(dá)93%，抑制炎癥發(fā)生達(dá)56%。VX-745作用于軟骨誘導(dǎo)性關(guān)節(jié)炎，呈現(xiàn)劑量反應(yīng)降低。 2.5, 5,和10 mg/kgVX-745作用于II型膠原誘導(dǎo)的關(guān)節(jié)炎鼠模型, 與對(duì)照組相比，在炎癥作用方面分別提高27%, 31%, 和44%。此外，VX-745保護(hù)32-39%的骨骼和軟骨

• 細(xì)胞實(shí)驗(yàn)： Cell lines: 人類骨髓基質(zhì)細(xì)胞 (BMSCs)和多發(fā)性骨髓瘤(MM)細(xì)胞 Concentrations: 60 nM-20 μM, 溶于DMSO. Incubation Time: 48小時(shí) Method: BMSCs(每孔5×104 個(gè)細(xì)胞)或MM細(xì)胞(每孔3×104個(gè)細(xì)胞)在96孔板上37 oC下溫育48小時(shí)。測(cè)定 [3H]-胸甘([3H]TdR)攝入率而測(cè)定DNA合成。細(xì)胞和[3H]TdR (每孔0.5 μCi) 在48小時(shí)培養(yǎng)期的最后8小時(shí)間進(jìn)行脈沖處理。測(cè)定MTT染料吸光值而測(cè)定VX-745抑制MM細(xì)胞和BMSCs生長(zhǎng)的效果

• 動(dòng)物實(shí)驗(yàn)： Animal Models: II型膠原誘導(dǎo)的關(guān)節(jié)炎(CIA)鼠模型 (DBA/1J) Dosages: 2.5, 5, 和 10 mg/kg Administration: 口服飼喂，每天兩次

• 參考文獻(xiàn)：
  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, 2000, June 16. 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.

• 溶解性： Soluble  in  DMSO

• 保存條件： 避光;-20°C

• 配置溶液濃度參考：
  

  	1mg	5mg	10mg
  1 mM	2.292 ml	11.461 ml	22.922 ml
  5 mM	0.458 ml	2.292 ml	4.584 ml
  10 mM	0.229 ml	1.146 ml	2.292 ml
  50 mM	0.046 ml	0.229 ml	0.458 ml

• 注意：部分產(chǎn)品我司僅能提供部分信息，我司不保證所提供信息的權(quán)威性，僅供客戶參考交流研究之用。

輸入產(chǎn)品批號(hào)：

本計(jì)算器可幫助您計(jì)算出特定溶液中溶質(zhì)的質(zhì)量、溶液濃度和體積之間的關(guān)系，公式為：

質(zhì)量 (mg) = 濃度 (mM) x 體積 (mL) x 分子摩爾量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *