原研机构 |
在研机构 |
非在研机构- |
最高研发阶段临床前 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
分子式C17H15F3N4 |
InChIKeyJOIONRWKOGDQOG-CYBMUJFWSA-N |
CAS号2499962-58-0 |
PINK1 loss-of-function mutations and exposure to mitochondrial toxins are causative for Parkinson’s disease (PD) and Parkinsonism, respectively. We demonstrate that pathological α-synuclein deposition, the hallmark pathology of idiopathic PD, induces mitochondrial dysfunction, and impairs mitophagy as evidenced by the accumulation of the PINK1 substrate pS65-Ubiquitin (pUb). We discovered MTK458, a brain penetrant small molecule that binds to PINK1 and stabilizes its active complex, resulting in increased rates of mitophagy. Treatment with MTK458 mediates clearance of accumulated pUb and α-synuclein pathology in α-synuclein pathology models in vitro and in vivo. Our findings from preclinical PD models suggest that pharmacological activation of PINK1 warrants further clinical evaluation as a therapeutic strategy for disease modification in PD.
适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
---|---|---|---|---|
帕金森病 | 临床2期 | 美国 | 2019-06-08 | |
神经退行性疾病 | 临床前 | - | - |
研究 | 分期 | 人群特征 | 评价人数 | 分组 | 结果 | 评价 | 发布日期 |
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No Data |