MERTK/AXL雙重激酶抗癌抑制劑開發

新成份新藥開發躍進計畫

運用國衛院生技藥研所之專利保護之特有激酶特異性小分子合成化物資料庫快速產出具MERTK與AXL雙效抑制劑，在鼠源三陰性乳癌4T1 動物模型中顯示BPR5K230抗癌活性優於AXL 選擇性試劑 BGB324 和 Pan TAM 激酶抑製劑 RXDX-106競爭藥物，並降低肺腫瘤發生率。在鼠源三陰性乳癌4T1 動物模型中顯示BPR5K230抗癌活性優於競爭藥物Ono-7475。優化先導化合物BPR5K294抗癌活性和競爭藥物Ono-7475同樣有效，對肝臟與腎臟指數無不良影響。我們將以5K230作後續候選發展藥物開發工作，以5K294作為備用後選發展藥物。

The criteria for candidate is 1. Good MERTK and AXL kinase selectivity, 2. Good oral bioavailability (F >20%), 3. Better anti-tumor efficacy than the benchmark compound, and 4. Good safety and toxicity profiles. We have identified a candidate-like optimized lead compound BPR5K230. 5K230 produced greater anti-tumor efficacy than benchmark compound ONO-7475 in murine TNBC tumor model at the same dose.We will nominate a developmental candidate and proceed preclinical development.