A New Topical Antiandrogen Benefits Acne Treatment

描述（由申请人提供）： 痤疮是医生遇到的最常见的皮肤病。它影响到80%的11至30岁的人。虽然整体健康不受损害，痤疮可以产生皮肤和情感的疤痕，持续一生。目前可用的疗法主要用于治疗症状，并伴有严重的缺点，如皮肤刺激，需要长期治疗，致畸和获得抗生素耐药性。需要更有效或更安全的治疗来实现患者更好的依从性。雄激素在痤疮的发展中起关键作用，即，疾病的起因理论上，使用雄激素阻断剂（例如抗雄激素）可预防或干预痤疮发病机制。然而，由于其对男性生育力的潜在副作用，全身性抗雄激素不能用于男性。即使在女性中，全身性抗雄激素也需要与口服避孕药一起使用。目前，没有可用的局部抗雄激素，并且在过去二十年中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，ASCJ 4，其诱导AR降解并在体外显示出上级抗雄激素活性。此外，我们发现ASCJ 4在局部应用于绒毛大鼠（人类痤疮的啮齿动物模型）后减弱皮脂腺。在这里，我们建议进一步研究ASCJ 4作为痤疮局部候选药物的潜力。我们将： 1.进行急性经皮毒性试验，考察ASCJ 4化合物的生物安全性; 2.研究更多的绒毛大鼠以证实ASCJ 4的皮脂腺抑制功效;以及 3.使用另一种广泛接受的人类痤疮啮齿动物模型，仓鼠胁腹器官，以确保ASCJ 4的皮脂抑制作用。 从这项研究中获得的信息将有助于确定ASCJ 4的安全性和有效性，并允许评估ASCJ 4是否可开发为痤疮的局部抗雄激素药物。

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.