Wang A-Min, Qiu Ru, Zhang Duo, Zhao Xiao-Yan
Bensheng Pharmaceuticals Co., Ltd., Room 102, 131 Kaiqing Road, East Zhangjiang, Pudong, Shanghai 201201, China.
Transl Oncol. 2022 Jan;15(1):101288. doi: 10.1016/j.tranon.2021.101288. Epub 2021 Nov 27.
BS-HH-002 is a newly developed drug with excellent antitumor activity, which resulted from the modification and optimization of the side structure of the homoharringtonine (HHT). It is particularly efficient in treatment for acute myeloid leukemia and myelodysplastic syndromes. Here we tested whether BS-HH-002 also had anti-cancer effects on solid tumors, especially pancreatic cancer. The results showed that BS-HH-002 treatment resulted in the complete degradation of the anti-apoptosis protein MCL-1, thereby inhibiting proliferation and inducing apoptosis of pancreatic cancer cells. In contrast, BCL-2 and BCL-XL protein levels were still detected in apoptotic cells. Further, we compared HHT and BS-HH-002 in terms of PK and heart toxicity in animals. Compared to HHT, BS-HH-002 quickly reached high blood concentration after intravenous injection or oral administration, without causing obvious cardiac toxicity. These results indicate that BS-HH-002 is a promising new anti-cancer drug to treat pancreatic and other solid tumors.
BS-HH-002是一种新开发的具有优异抗肿瘤活性的药物，它是通过对高三尖杉酯碱（HHT）的侧链结构进行修饰和优化而得到的。它在治疗急性髓系白血病和骨髓增生异常综合征方面特别有效。在此，我们测试了BS-HH-002对实体瘤尤其是胰腺癌是否也具有抗癌作用。结果表明，BS-HH-002处理导致抗凋亡蛋白MCL-1完全降解，从而抑制胰腺癌细胞的增殖并诱导其凋亡。相比之下，在凋亡细胞中仍可检测到BCL-2和BCL-XL蛋白水平。此外，我们在动物体内比较了HHT和BS-HH-002的药代动力学和心脏毒性。与HHT相比，BS-HH-002静脉注射或口服给药后能迅速达到高血药浓度，且不会引起明显的心脏毒性。这些结果表明，BS-HH-002是一种有前景的新型抗癌药物，可用于治疗胰腺癌和其他实体瘤。
