槲皮素对 kras g12d 的治疗作用
一、槲皮素与 kras g12d的结合亲和力超过正在临床试验的 kras g12d 靶向药 MRTX1133《The discovery of some promising putative binders of KRAS G12D receptor using computer-aided drug discovery approach》
The study revealed 3 promising compounds (Quercetin, Psoralidin, and Resveratrol) with lower binding energy (−9.4 kcal/mol, −8.4 kcal/mol, and −8.4 kcal/mol respectively) compared to the referenced ligand-MRTX1133 (−8.3 kcal/mol)
二、槲皮素可以用到很高的剂量
槲皮素这些植物素的一大缺点就是吸收不好，生物利用度低；代谢时间短。
解决办法一是把槲皮素做成纳米脂质体乳化剂吃，增加生物利用度，延长代谢时间。
二是加大剂量吃。
《A Phase I Dose Escalation Study Demonstrates Quercetin Safety and Explores Potential for Bioflavonoid Antivirals in Patients with Chronic Hepatitis C》 这篇论文讲了一个用槲皮素治疗丙肝的临床试验；其中一组剂量是每天吃5克槲皮素，耐受良好，没有不良反应和毒副作用。因为还没有达到最大耐受剂量，因此患者可以在自己耐受的基础上，甚至探索更高的剂量。
Quercetin doses ranged from 250 to 5000 mg/day (Table 2). There were three patients per dose group, with the exception of three dose levels (2000, 3000, and 4000 mg/day), which had only two patients per group because of withdrawal from the study. High doses were well tolerated, with no adverse events or signs of toxicity. The MTD was not reached during the trial. There was no notable change from baseline measurement to week 2 and 4 measurements for complete blood count, complete metabolic panel, cholesterol panel, and coagulation study.
三、槲皮素是p-gp蛋白 抑制剂；联用其他是p-gp底物的抗癌药时可能会加大此类药物的血药浓度；要注意这点。
《Screening dietary flavonoids for the reversal of P-glycoprotein-mediated multidrug resistance in cancer》
It has been found that quercetin and rutin were the highly desirable flavonoids for the inhibition of P-gp transport function and they significantly reduced resistance in cytotoxicity assays to paclitaxel in P-gp overexpressing MDR cell lines.
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