A-205804

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Chemical Structure| 251992-66-2 同义名 : -
CAS号 : 251992-66-2
货号 : A526825
分子式 : C15H12N2OS2
纯度 : 98%
分子量 : 300.4
MDL号 : MFCD09038566
存储条件：

Pure form Sealed in dry, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
靶点

  • Integrin

    E-selectin, IC50:20 nM

    ICAM-1, IC50:25 nM
描述 Cell adhesion molecules (CAMs) are a group of cell surface proteins involved in mediating adhesion of cells to each other and extracellular matrix proteins, including E-selection, ICAM-1, and VCAM-1. The interaction of CAMs on vascular endothelial cells with their counter-receptors on circulation leukocytes, such as Lewis-X antigens, β1 and β2 integrins, leads to the transmigration of leukocytes to the site of injury. A-2058804 is a potent selective inhibitor of E-selectin and ICAM-1 with IC50 values of 20nM and 25nM, respectively[3]. Treatment of a monolayer of HUVECs with 0.1 μM A-205804 exhibited markedly decreased adhesion of flowing human leukocytic cells (HL60) by 60% as monitored by video microscopy. However, A-205804 did not inhibit human T-cell proliferation in tetanus toxoid or Staphylococcus enterotoxin stimulated proliferation assays at concentrations ranging from 5 to 20μM. In vitro, A-205804 inhibited the proliferation of HUVECs with IC50 value of 152nM[3]. In vivo, oral administration of A-205804 produced A-245346 and A-236934 in the plasma of rat[3]. Treatment C56BL/6 mice with A-205804 at 25~100mg/kg three times a week for two weeks indeed efficiently decrease the expression of E-selection on the endothelial vascular niche cells [4].
作用机制 A-205804 noncovalently bound to a macromolecule or complex in the cell nucleus with a molecular weight greater than 650kDa[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.33mL

0.67mL

0.33mL

16.64mL

3.33mL

1.66mL

33.29mL

6.66mL

3.33mL
参考文献

[1]Zhu GD, Arendsen DL, et al. Selective inhibition of ICAM-1 and E-selectin expression in human endothelial cells. 2. Aryl modifications of 4-(aryloxy)thieno[2,3-c] pyridines with fine-tuning at C-2 carbamides. J Med Chem. 2001 Oct 11;44(21):3469-87.

[2]Stewart AO, Bhatia PA, et al. Discovery of inhibitors of cell adhesion molecule expression in human endothelial cells. 1. Selective inhibition of ICAM-1 and E-selectin expression. J Med Chem. 2001 Mar 15;44(6):988-1002.

[3]Stewart A O, Bhatia P A, Mccarty C M, et al. Discovery of inhibitors of cell adhesion molecule expression in human endothelial cells. 1. Selective inhibition of ICAM-1 and E-selectin expression. Journal of Medicinal Chemistry. 2001;44(6):988-1002

[4] Morita K, Tokushige C, Maeda S, Kiyose H, Noura M, Iwai A, Yamada M, Kashiwazaki G, Taniguchi J, Bando T, Hirata M, Kataoka TR, Nakahata T, Adachi S, Sugiyama H, Kamikubo Y. RUNX transcription factors potentially control E-selectin expression in the bone marrow vascular niche in mice. Blood Adv. 2018 Mar 13;2(5):509-515

[5] Zhu GD, Schaefer V, Boyd SA, Okasinski GF. Synthesis and mode of action of (125)I- and (3)H-labeled thieno[2,3-c]pyridine antagonists of cell adhesion molecule expression. J Org Chem. 2002 Feb 8;67(3):943-8