Selective Matrix Metalloproteinase Inhibitors For Osteoarthritis

描述（由申请人提供）：Aquilus Pharmaceuticals，Inc.提出评估两种新型基质金属蛋白酶（MMP）抑制剂在内侧膝关节撕裂（MMT）和单碘乙酸盐（MIA）骨关节炎（OA）大鼠模型中的作用，并伴有疼痛读数。I期的目标是扩大变构、MMP-13和双重活性MMP-2/-9抑制剂的合成，确定它们的药代动力学（PK），并在MMT和MIA-大鼠OA模型中进行动物疗效研究。拟议工作的最终目标是评估是否可以开发一种选择性MMP抑制剂用于治疗OA。 公共卫生相关性：骨关节炎（OA）影响估计2000万人，约占初级保健医生办公室就诊的25%，占所有非甾体抗炎药（NSAID）疼痛处方的一半。在OA疼痛治疗市场中，对于不仅减轻关节疼痛而且治疗疾病本身的药物仍然存在大量未满足的需求。目前，市场上没有治疗骨关节炎疼痛的疾病修饰药物。Aquilus制药公司将在两种OA动物疼痛模型中测试一系列负责软骨降解的蛋白质的高效抑制剂。如果成功，Aquilus制药公司将能够迅速为临床带来一流的药物，不仅可以减少与OA相关的疼痛，还可能阻止或减缓疾病进展，并最终需要关节置换手术。

DESCRIPTION (provided by applicant): Aquilus Pharmaceuticals, Inc. proposes to evaluate the effects of two novel matrix metalloproteinase (MMP) inhibitors in both the medial meniscal tear (MMT) and monoiodoacetate (MIA) rat models of osteoarthritis (OA) with pain read-outs. The goals for Phase I are to scale-up the synthesis of the allosteric, MMP-13 and dual active MMP-2/-9 inhibitors, determine their pharmacokinetics (PK) and run animal efficacy studies in both the MMT and MIA-rat models of OA. The ultimate goal of the proposed work is to evaluate whether a selective MMP inhibitor can be developed for the treatment of OA. PUBLIC HEALTH RELEVANCE: Osteoarthritis (OA) affects an estimated 20 million people and accounts for roughly 25% of office visits to primary care physicians and half of all nonsteroidal anti-inflammatory drug (NSAID) prescriptions for pain. Within the OA pain therapy market there remains a substantial unmet need for drugs that not only reduce joint pain but also treat the disease itself. Currently, there are no diseases modifying drugs in the market to treat Osteoarthritc pain. Aquilus Pharmaceuticals will test a series of highly potent inhibitors of proteins responsible for cartilage degradation in two OA animal pain models. If successful, Aquilus Pharmaceuticals will be able to rapidly bring to the clinic a first in class drug that not only can reduce pain associated with OA but also possibly halt or slow down the disease progression and the eventual need for joint replacement surgery.