Development of a MMP Inhibitor for Neuropathic Pain

神经性疼痛 MMP 抑制剂的开发

• 批准号: 9115128
• 负责人: IRVING SUCHOLEIKI
• 金额: $ 137.52万
• 依托单位: AQUILUS PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-04 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9115128
• 关键词: Acids; Adverse effects; Affect; American; Animal Model; Animals; Award; Benzene; Biological Availability; Biological Markers; Canis familiaris; Chronic; Clinic; Clinical; Development; Disseminated Malignant Neoplasm; Drops; Exhibits; Gelatinase A; Goals; Grant; Health; Human; In Vitro; Investigational Drugs; Ligation; Matrix Metalloproteinase Inhibitor; Maximum Tolerated Dose; Modeling; Nerve; Oral; Pain; Parents; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Substance; Pharmacology; Pharmacotherapy; Phase; Plasma; Process; Rattus; Rodent; Rodent Model; Running; Safety; Scheme; Small Business Innovation Research Grant; Spinal nerve structure; Testing; Tissues; Toxic effect; Work; acute toxicity; addiction; analytical method; chronic constriction injury; chronic neuropathic pain; good laboratory practice; improved; inhibitor/antagonist; mechanical allodynia; meetings; method development; mouse model; novel; orofacial; painful neuropathy; pre-clinical; research and development; research study; safety study; scale up

 DESCRIPTION (provided by applicant): Aquilus Pharmaceuticals, Inc. proposes to preclinically develop AQU-118 for the treatment of orofacial and general neuropathic pain via a newly discovered mechanism involving matrix metalloproteinases-2 & 9 (MMP-2, MMP-9). AQU-118 is a non-hydroxamic acid containing, MMP inhibitor that is selective for both MMP-2 and MMP-9 and has been shown to block mechanical allodynia in both the spinal nerve ligation (SNL) and the chronic constriction injury of the infraorbital nerve (CCI-IoN) rodent models of neuropathic pain. The goals for Phase II are to scale-up the synthesis of AQU-118, determine its phamacokinetics & phamacodynamics (PK/PD) in the SNL-rat model and complete in-vitro safety studies within the first year. Year two will entail the process research & development (PRD) of the synthetic scale- up of AQU-118 culminating in its GMP manufacture as well completing various pivotol GLP animal toxicity studies. The ultimate goal of the proposed work is to rapidly develop a safe and effective drug for the treatment of chronic orofacial and general neuropathic pain that produces no addictive or euphoric side-effects.



项目成果

Biomarker Analysis of Orally Dosed, Dual Active, Matrix Metalloproteinase (MMP)-2 and MMP-9 Inhibitor, AQU-118, in the Spinal Nerve Ligation (SNL) Rat Model of Neuropathic Pain.

在脊髓神经结扎 (SNL) 大鼠神经性疼痛模型中口服双活性基质金属蛋白酶 (MMP)-2 和 MMP-9 抑制剂 AQU-118 的生物标志物分析。

• DOI: 10.3390/ijms20040811
• 发表时间: 2019
• 期刊: International journal of molecular sciences
• 影响因子: 5.6
• 作者: Kwan,MeiYee;Choo,Anthony;Hanania,Taleen;Ghavami,Afshin;Beltran,Jose;Shea,John;Barboza,Amidi;Hu,Andrew;Fowler,Marcie;Neelagiri,VenugopalRao;Sucholeiki,Irving
• 通讯作者: Sucholeiki,Irving