An expanded view of the substrate landscape of organic anion transporting polypeptide (OATP) 2B1 was pursued with the goal of understanding if the identification of novel in vitro substrates could shed additional light on the impact of OATP2B1 on intestinal absorption and brain penetration.

To examine this hypothesis, a series of experiments measured the cellular accumulation of a diverse array of compounds. Representative angiotensin II receptor blockers (ARBs) and other compounds of interest were subsequently investigated for inhibition, time dependence, and kinetics.

The study identified ARBs as a class of OATP2B1 substrates and found balsalazide, olsalzine, and gavestinel to be novel substrates of OATP2B1 too. Some compounds previously reported to be OATP2B1 substrates in the literature, aliskiren, erlotinib, montelukast, fexofenadine, and taurocholate could not be confirmed as substrates.

Literature describing in vivo outcomes for OATP2B1 substrates, coproporphyrin III, ARBs, balsalazide, olsalzine, and gavestinel highlight the absence of a substantial impact of OATP2B1 on the oral absorption and/or brain penetration of OATP2B1 substrates. Suggestions of including OATP2B1 assessment as part of the drug approval process are likely premature and further mechanistic work with more robust OATP2B1 substrates, which may include some of those described here, is desirable.

寻求有机阴离子转运多肽（OATP）2B1的底物景观的扩展视图，目的是了解新型体外底物的鉴定是否可以进一步阐明OATP2B1对肠吸收和脑渗透的影响。

为了检验这一假设，一系列实验测量了多种化合物的细胞积累。随后研究了代表性的血管紧张素II受体阻滞剂（ARB）和其他感兴趣的化合物的抑制作用，时间依赖性和动力学。

这项研究将ARBs鉴定为OATP2B1的一类底物，并且发现巴拉沙肼，奥沙尔嗪和木槌酚也是OATP2B1的新底物。以前在文献中报道过一些化合物是OATP2B1底物，阿利吉仑，厄洛替尼，孟鲁司特，非索非那定和牛磺胆酸盐不能被确认为底物。

描述OATP2B1底物，共卟啉III，ARB，巴尔沙拉肽，olsalzine和木马汀的体内结果的文献强调，OATP2B1对OATP2B1底物的口服吸收和/或脑渗透没有实质性影响。建议将OATP2B1评估作为药物批准过程的一部分，还为时过早，并且需要使用更坚固的OATP2B1底物（可能包括此处所述的一些底物）进行进一步的机械工作。