blood：新药物可无害治愈血栓
RUC-1 可以使药物分子作用于血块而没其他副作用
（图片来源：洛克菲勒大学）
血液中的血小板可以在受伤时帮助血液凝固而止血，可当正常血管中的血小板凝固就会结成血块，堵塞血管对心脏造成伤害。洛克菲勒大学的科学家近日发明了一种新的药物可以迅速溶解血管中的血块，及时阻止其对血管的伤害。
科学家说这种新药避免了传统药物对机体造成的损伤和危害，可以口服达到溶解血块的目的。这项研究发表在最新一期的《血液》上面。（生物谷编译）
生物谷推荐原始出处：
DOI 10.1182/blood-2007-08-105544
Application of high-throughput screening to identify a novel 
IIb-specific small- molecule inhibitor of IIbβ3-mediated platelet interaction with fibrinogen
ková1
1 Laboratory of Blood and Vascular Biology, The Rockefeller University, New York, NY; 2 Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY; and 3 High Throughput Screening Resource Center, The Rockefeller University, New York, NY
Small-molecule 
IIbβ3 antagonists competitively block ligand binding by spanning between the D224 in IIb and the MIDAS metal ion in β3. They variably induce conformational changes in the receptor, which may have undesirable consequences. To identify IIbβ3 antagonists with novel structures, we tested 33 264 small molecules for their ability to inhibit the adhesion of washed platelets to immobilized fibrinogen at 16 µM. A total of 102 compounds demonstrated 50% or more inhibition, and one of these (compound 1, 265 g/mol) inhibited ADP-induced platelet aggregation (IC50: 13± 5 µM), the binding of soluble fibrinogen to platelets induced by mAb AP5, and the binding of soluble fibrinogen and a cyclic RGD peptide to purified IIbβ3. Compound 1 did not affect the function of GPIb, 2β1, or the other β3 family receptor Vβ3. Molecular docking simulations suggest that compound 1 interacts with IIb but not β3. Compound 1 induced partial exposure of an IIb ligand-induced binding site (LIBS), but did not induce exposure of 2 β3 LIBS. Transient exposure of purified IIbβ3 to eptifibatide, but not compound 1, enhanced fibrinogen binding ("priming"). Compound 1 provides a prototype for small molecule selective inhibition of IIbβ3, without receptor priming, via targeting IIb.
- 众说风云 (已有0条评论)
