CGP 77675

CGP 77675 is a kind of potent inhibitor of the tyrosine kinase Src which inhibits autophosphorylation of purified Src with an IC₅₀ value of 40nM ^[1]. CGP 77675 potently inhibits tyrosine phosphorylation of the Src substrates Fak and paxillin ^[1]. CGP 77675 has the potential to treat primary prostate cancers and diseases associated with elevated bone loss ^{[1, 2]}.

CGP 77675 (0.1~10μM; 5d) inhibited the parathyroid hormone (PTH)-stimulated release of ⁴⁵Ca in a concentration-dependent manner in the fetal rat long bone organ culture system ^[1]. CGP 77675 (2μM; 30min) reduced adhesion of PC3 cells; CGP 77675 (0.1~10μM; 30min) decreased [³H]-thymidine incorporation in serum-starved PC3 cells ^[2].

CGP 77675 (1, 5 and 25mg/kg; 4d; bid; s.c.) inhibited IL-1β-induced hypercalcemia, lowered the serum calcium concentration in the male mice; CGP 77675 (5 and 20mg/kg; 6 weeks; bid; p.o.) reduced bone loss induced by ovariectomy in the female Sprague-Dawley rats ^[1].

References:
[1] Missbach M, Jeschke M, Feyen J, et al. A novel inhibitor of the tyrosine kinase Src suppresses phosphorylation of its major cellular substrates and reduces bone resorption in vitro and in rodent models in vivo [J]. Bone, 1999, 24(5): 437-449.
[2] Recchia I, Rucci N, Festuccia C, et al. Pyrrolopyrimidine c-Src inhibitors reduce growth, adhesion, motility and invasion of prostate cancer cells in vitro [J]. European journal of cancer, 2003, 39(13): 1927-1935.

CGP 77675是一种高效的酪氨酸激酶Src抑制剂，其抑制纯化Src的自磷酸化反应的IC₅₀为 40nM^[1]。CGP 77675能有效抑制Src底物Fak和paxillin的酪氨酸磷酸化^[1]。CGP 77675具有治疗原发性前列腺癌以及与骨丢失相关的疾病的潜力^{[1, 2]}。

CGP 77675（0.1~10μM；5d）在胎鼠长骨组织培养体系中，以浓度依赖的方式抑制了甲状旁腺激素（PTH）刺激的⁴⁵Ca的释放^[1]。CGP 77675（2μM；30min）降低了PC3细胞的黏附能力；CGP 77675（0.1~10μM；30min）减少了饥饿血清培养的PC3细胞中[³H]-胸腺嘧啶核苷的掺入^[2]。

CGP 77675（1，5和25mg/kg；4d；bid；s.c.）抑制了IL-1β引起的高钙血症，降低了雄性小鼠的血钙浓度；CGP 77675（5和20mg/kg；6 weeks；bid；p.o.）减少雌性Sprague-Dawley大鼠因卵巢切除而产生的骨丢失^[1]。