生物活性

Adezmapimod (SB 203580) is a selective and ATP-competitive p38 MAPK inhibitor with IC₅₀s of 50 nM and 500 nM for SAPK2a/p38 and SAPK2b/p38β2, respectively. Adezmapimod inhibits LCK, GSK3β and PKBα with IC₅₀s of 100-500-fold higher than that for SAPK2a/p38. Adezmapimod does not disrupt JNK activity and is an autophagy and mitophagy activator

IC₅₀ & Target：

^{p38：50 nM (IC₅₀)}

p38β2：500 nM (IC₅₀)

體外研究(In Vitro)：

Adezmapimod (SB 203580) (preincubated with 0-30 μM for 1 h and cultured for 24 h in the presence of 20 ng/mL IL-2) prevents the IL-2-induced proliferation of primary human T cells, murine CT6 T cells, or BAF F7 B cells with an IC₅₀ of 3-5 μM[1].
SB203580 blocks PKB phosphorylation (IC₅₀ 3-5 μM). SB203580 inhibitsthe phosphorylation of Ser473 in a dose-dependent manner in both CT6 and activated human T cells and IL-2-responsive BA/F3 F7 B cells

Cell Line:CT6, BA/F3 cell line F7, and PBMC/T cells

Concentration:0-30 μM

Incubation Time:Preincubated with 0-30 μM SB203580 for 1 h and cultured for 24 h in the presence of 20 ng/mL IL-2

Result:Prevented the IL-2-induced proliferation of primary human T cells, murine CT6 T cells, or BAF F7 B cells with an IC₅₀ of 3-5 μM.

體內(nèi)研究(In Vivo)

Adezmapimod (SB 203580) (5 mg/kg/day; intra peritoneal injected daily for 16 consecutive days, in female atymic Nu/Nu mice) treatment, p38WT tumors show a significantly smaller tumor burden when compared with p38TM tumors that were treated in parallel

Animal Model:Six-week-old female atymic Nu/Nu mice CAL27 p38WT and p38TM tumors

Dosage:5 mg/kg/day

Administration:Intra peritoneal injected daily for 16 consecutive days

Result:After 2 weeks treatment, CAL27 p38WT tumors were significantly smaller; CAL27 p38TM tumors were not affected by the p38 inhibitor (n=10).

分子量：377.43

Formula：C₂₁H₁₆FN₃OS

CAS 號(hào)：152121-47-6

運(yùn)輸條件：Room temperature in continental US; may vary elsewhere.

儲(chǔ)存方式：

溶解性數(shù)據(jù)

請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥方式選擇適當(dāng)?shù)娜芙夥桨?。以下溶解方案都?qǐng)先按照 In Vitro 方式配制澄清的儲(chǔ)備液，再依次添加助溶劑：

——為保證實(shí)驗(yàn)結(jié)果的可靠性，澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的工作液，建議您現(xiàn)用現(xiàn)配，當(dāng)天使用； 以下溶劑前顯示的百
分比是指該溶劑在您配制終溶液中的體積占比；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的方式助溶

• 1.

  
  

  請(qǐng)依序添加每種溶劑： 5% DMSO    40% PEG300    5% Tween-80    50% saline

  Solubility: ≥ 2.5 mg/mL (6.62 mM); Clear solution

  
  

• 2.

  
  

  請(qǐng)依序添加每種溶劑： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 1.56 mg/mL (4.13 mM); Clear solution

• 3.

  
  

  請(qǐng)依序添加每種溶劑： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 1.56 mg/mL (4.13 mM); Clear solution

• 4.

  
  

  請(qǐng)依序添加每種溶劑： 10% DMSO    90% corn oil

  Solubility: ≥ 1.56 mg/mL (4.13 mM); Clear solution

參考文獻(xiàn)

[1]. Davies SP, et al. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.

[2]. Lali FV, et al. The pyridinyl imidazole inhibitor SB203580 blocks phosphoinositide-dependent protein kinase activity, protein kinase B phosphorylation, and retinoblastoma hyperphosphorylation in interleukin-2-stimulated T cells independently of p38 mitogen-activated protein kinase. J Biol Chem. 2000 Mar 10;275(10):7395-402.

[3]. Leelahavanichkul K, et al. A role for p38 MAPK in head and neck cancer cell growth and tumor-induced angiogenesis and lymphangiogenesis. Mol Oncol. 2014 Feb;8(1):105-18.