A New Topical Antiandrogen Benefits Acne Treatment

一种新的外用抗雄激素有益于痤疮治疗

• 批准号: 6831937
• 负责人: CHARLES C-Y SHIH
• 金额: $ 10万
• 依托单位: ANDROSCIENCE CORPORATION
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-19 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6831937
• 关键词: SDS polyacrylamide gel electrophoresis; acne; androgen inhibitor; biological models; dosage; drug discovery /isolation; hamsters; hormone sensitivity /resistance; keratosis; laboratory rat; mass spectrometry; pharmacokinetics; sebaceous glands; skin disorder chemotherapy; topical drug application; western blottings

DESCRIPTION (provided by applicant): Acne is the most common skin disorder encountered by physicians. It affects 80% of all persons between the ages of 11 and 30 years. Although the overall health is not impaired, acne can produce cutaneous and emotional scars that last a lifetime. Currently available therapies are mainly used to treat symptoms and are associated with severe drawbacks, such as skin irritation, requiring prolonged treatment, teratogenesis, and acquisition of antibiotic resistance. More effective or safer treatments are needed to achieve a better compliance in the patient. Androgens play a critical role in the development of acne, i.e., the cause of disease. In theory, use of androgen blockers (e.g. anti-androgens) would prevent or intervene in acne pathogenesis. Nevertheless, systemic anti-androgens cannot be used in men due to its potential side effect in male fertility. Even in women, systemic anti-androgens need to be prescribed in conjunction with oral contraceptives. Currently, there is no topical anti-androgen available, and search for an effective topical antiandrogen has been going on for the last two decades. Recently, we discovered a new class of anti-androgen, ASCJ4, which induces AR degradation and displaying a superior anti-androgen activity in vitro. Furthermore, we discovered that ASCJ4 after topically applied to fuzzy rats (a rodent model for human acne) attenuates seborrhea. In here, we propose to further study ASCJ4's potentiality as a topical drug candidate for acne. We will: 1. Perform acute dermal toxicity test to examine biosafety of ASCJ4 compound; 2. Study more fuzzy rats to confirm the sebaceous gland repressive efficacy of ASCJ4; and 3. Use another widely accepted rodent model for human acne, the hamster flank organs, to ensure the sebosuppressive effect of ASCJ4. The derived information from this study will help define the ASCJ4's safety and efficacy and allow an evaluation as to whether ASCJ4 is developable as a topical anti-androgen drug for acne.

描述（由申请人提供）： 痤疮是医生遇到的最常见的皮肤病。它影响了11至30岁之间所有人中的80％。尽管整体健康没有受损，但痤疮可以产生一生的皮肤和情感疤痕。目前可用的疗法主要用于治疗症状，并与严重的缺点（例如皮肤刺激）相关，需要长时间的治疗，致畸作用和抗生素耐药性。需要更有效或更安全的治疗方法来实现患者的更好依从性。雄激素在痤疮的发展中起着至关重要的作用，即疾病的原因。从理论上讲，使用雄激素阻滞剂（例如抗雄激素）将预防或干预痤疮发病机理。然而，由于男性在男性生育方面的潜在副作用，因此无法在男性中使用全身性抗雄激素。即使在女性中，系统性抗雄激素也需要与口服避孕药一起开处方。当前，尚无局部抗雄激素可用，在过去的二十年中，人们一直在寻找有效的局部抗雄激素。最近，我们发现了一类新的抗雄激素ASCJ4，该抗雄激素在体外诱导AR降解并显示出优质的抗雄激素活性。此外，我们发现ASCJ4在局部应用于模糊大鼠（人痤疮的啮齿动物模型）后减弱了脂肪。在这里，我们建议进一步研究ASCJ4作为痤疮局部药物的潜力。我们将： 1。进行急性皮肤毒性测试检查ASCJ4化合物的生物安全； 2。研究更多模糊的大鼠，以确认ASCJ4的皮脂腺抑制功效；和 3。使用另一个广泛接受的啮齿动物模型，用于人痤疮，仓鼠侧心器官，以确保ASCJ4的抑制效果。 从这项研究中得出的信息将有助于定义ASCJ4的安全性和功效，并允许对ASCJ4是否可以作为局部抗雄激素药物进行评估。