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

用选择性 CDK 抑制剂 R-roscovit 治疗垂体库欣病

基本信息

批准号：
8773516
负责人：
SHLOMO MELMED
金额：
$ 23.44万
依托单位：
CEDARS-SINAI MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8773516
关键词：
Adrenal Gland Hyperfunction Adrenal Glands Adrenalectomy Adverse effects Age Apoptosis Applications Grants CDC2 Protein Kinase CDK2 gene CYC 202 Cardiovascular Diseases Cause of Death Cell Cycle Cell Cycle Arrest Cell Proliferation Central obesity Clinical Trials Comorbidity Corticotropin Cultured Tumor Cells Cyclin E Data Diabetes Mellitus Disease Disease model Dose E2F1 gene Evaluation FDA approved Future Genes Glucocorticoids Hormones Human Hydrocortisone Hyperglycemia Hypertension Infection Insulin Intervention Laboratories Laboratory Research Lead Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of nasopharynx Medical Medical center Mental disorders Metabolic Modality Modeling Mus Neurosecretory Systems Non-Small-Cell Lung Carcinoma Operative Surgical Procedures Oral Osteoporosis Patients Pharmacologic Substance Pharmacotherapy Phase Phase II Clinical Trials Phase III Clinical Trials Pituitary Corticotropin Secreting Adenoma Pituitary Gland Pituitary-dependent Cushing&apos s disease Preparation Pro-Opiomelanocortin Production Protein Dephosphorylation Radiation Recruitment Activity Risk Role Route Safety Serous Testing Therapeutic Thrombosis Translating Zebrafish base clinical practice disorder control drug development inhibitor/antagonist innovation mortality neoplastic neoplastic cell novel pre-clinical public health relevance purine analog research and development roscovitine sex small molecule somatostatin analog standard of care tumor tumor growth urinary

项目摘要

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.

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。