Treatment of pituitary Cushing disease with a selective CDK inhibitor, R-roscovit

描述（由申请人提供）：我们从创新的实验室研究中发现了R-roscovitine，这是一种选择性CDK抑制剂，具有抑制垂体促肾上腺皮质激素肿瘤细胞增殖和ACTH产生的双重作用。我们现在提出了一个试点，概念验证的II期临床试验，以治疗与促肾上腺皮质激素肿瘤（库欣病），谁是从雪松-西奈医学中心的垂体中心招募的患者，以确定是否R-roscovitine可以安全地正常化尿游离皮质醇水平，通过减少垂体促肾上腺皮质激素肿瘤ACTH的生产。R-roscovitine已经进行了几种恶性肿瘤的I期和II期临床试验，如果对皮质激素肿瘤有效，其口服给药途径和相对轻微的副作用使库欣病的每日长期治疗成为可能。我们的研究将探索一种新的干预措施，用于急需的直接靶向垂体促肾上腺皮质激素肿瘤的药物治疗策略，垂体促肾上腺皮质激素肿瘤是最具挑战性的人类神经内分泌疾病之一。

DESCRIPTION (provided by applicant): Our discovery from innovative laboratory research has led to the identification of R-roscovitine, a selective CDK inhibitor with dual effect suppressing both cell proliferation and ACTH production in pituitary corticotroph tumors. We now propose a pilot, proof of concept phase II clinical trial to treat with R-roscovitine of patiens with corticotroph tumors (Cushing disease), who are recruited from the Pituitary Center at Cedars-Sinai Medical Center, to determine if R-roscovitine can safely normalize urinary free cortisol levels by reducing pituitary corticotroph tumor ACTH production. R-roscovitine has been undergoing phase I and II clinical trials for several malignancies, and, if effective for corticotrph tumors, its oral dosing route and relatively mild side effects make daily long-term treatment of Cushing disease feasible. Our study will explore a novel intervention for much needed pharmaco-therapeutic strategies directly targeting pituitary corticotroph tumors, one of the most challenging human neuroendocrine diseases.