Technical Name Development of Neuroprotective Agent DBPR168 against Chemotherapy-Induced Peripheral Neuropathy
Project Operator National Health Research Institutes
Project Host 夏克山
Approximately, 60-70 patients develop chemotherapy-induced peripheral neuropathy after receiving paclitaxel, a first-line chemotherapeutic agent. DBPR168 has completed the proof-of-principle in mouse models of paclitaxel-induced neuropathy, including the tail immersionvon Frey filament tests. Pretreatment with DBPR168 before paclitaxel was able to effectively alleviate both paclitaxel-induced thermal hypesthesiamechanical allodynia significantly. DBPR168 has a high safety dose (500 mg/kg)a low minimum efficacy dose (10 mg/kg) in mice, thus having great potential to become the first-in-class neuroprotective agent to prevent CIPN in the future.
Scientific Breakthrough
Through combining a high-content screening platform with a novel neurite outgrowth assay on a series of more than 300 derivatives designed based on the initial hit compound CSV0A024807, we have discovered a promising neuroprotective agent DBPR168 against paclitaxel-induced neuropathy. DBPR168 has completed two animal behavioral models in mice, including the tail immersionvon Frey filament tests, verifying that it can significantly protectalleviate peripherally neural damage caused by paclitaxel treatment. Mechanistically, DBPR168 appears to inhibit paclitaxel-induced inflammatory responsesthe infiltration of immune cells into sensory neurons as reflected by the reduction of various inflammatory factorschemokines.
Industrial Applicability
Breastlung cancers are two leading causes of cancer incidences all over the world,paclitaxel, serving as the first-line agent, plays an important role in their chemotherapies. However, paclitaxel-induced peripheral neuropathy occurs frequently during treatment, not only leading to diminishing quality of life but even making patients suspend therapy. As demonstrated by two disease animal models, pretreatment with DBPR168 can effectively protect CIPN caused by paclitaxel. To date, 16 marketed drugs have been attempted to prevent CIPN, but they all failed. Based on a high therapeutic window (50),excellent efficacy, we believe that DBPR168 may have great potential to become the first-in-class agent against CIPN.
Keyword chemotherapy-induced peripheral neuropathy neuroprotective agent paclitaxel neurite outgrowth assay pro-inflammatory cytokine chemokine macrophage
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  • Kak-Shan Shia
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