ADH-503

CD11b/CD18 is a dimeric integrin highly expressed on the surface of myeloid cells and plays an important role in transendothelial migration and tissue recruitment during inflammatory immune responses. ADH-503 is a small-molecule allosteric agonist of CD11b/CD18 that partially actives CD11b conformation through binding. It increased CD11b/CD18-dependent cell adhesion to fibrinogen with an EC50 value of 4 mM. Treatment of leukocytes with 15 μM ADH-503 led to a significant decrease in lateral migration and migration velocity compared to DMSO-treated controls. The intravital microscopic analysis of mouse cremaster muscle showed that ADH-503 at 100 μM decreased the rolling velocity of leukocytes in TNF-α-treated venules. In a mouse model of acute, thioglycolate-induced peritonitis, administration of ADH-503 (200 μL of a 50 μM solution in saline) 30 min before thioglycolate injection reduced the amount of neutrophil accumulation by 40% compared to vehicle-pretreated mice. Also, neutrophil accumulation in ADH-503-treated mice was reduced at 4 h after thioglycolate injection and stayed reduced at 12 h¹.

溶解方案(细胞实验)

Methanol 中的溶解度 : 100 mg/mL (190.60 mM; 超声助溶)|DMSO 中的溶解度 : 21.43 mg/mL (40.85 mM; 超声助溶; 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)|Ethanol 中的溶解度 : 3.33 mg/mL (6.35 mM; 超声助溶 (<60°C))

溶解方案(动物实验)

"方案 一": "请依序添加每种溶剂：10% DMSO 90% (20% SBE-β-CD in Saline)Solubility: ≥ 2.14 mg/mL (4.08 mM); 澄清溶液 此方案可获得 ≥ 2.14 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 21.4 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液 中，混合均匀。2 g SBE-β-CD（磺丁基醚 β-环糊精）粉末定容于 10 mL 的生理盐水中，完全溶解至澄清透明。"

"方案 二": "请依序添加每种溶剂：10% DMSO 90% Corn OilSolubility: ≥ 2.14 mg/mL (4.08 mM); 澄清溶液 此方案可获得 ≥ 2.14 mg/mL（饱和度未知）的澄清溶液，此方案实验周期在半个月以上的动物实验酌情使用。以 1 mL 工作液为例，取 100 μL 21.4 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。"

"方案 三": "请依序添加每种溶剂：10% DMSO 40% PEG300 5% Tween-80 45% SalineSolubility: 2.08 mg/mL (3.96 mM); 悬浊液; 超声助溶 此方案可获得 2.08 mg/mL的均匀悬浊液，悬浊液可用于口服和腹腔注射。以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；再向上述体系中加入 50 μL Tween-80，混合均匀；然后再继续加入 450 μL 生理盐水 定容至 1 mL。生理盐水的配制：将 0.9 g 氯化钠，溶解于 ddH₂O 并定容至 100 mL，可以得到澄清透明的生理盐水溶液。"