BCH (LAT1-IN-1) is a selective and competitive inhibitor of the L-type amino acid transporter 1 (LAT1). BCH inhibits cancer cell growth and induces apoptosis by suppressing cellular amino acid uptake and mTOR phosphorylation. BCH can be used in research related to cancers such as esophageal cancer[1-4].
In vitro, BCH (10mM) treated endometrial cancer cell lines (Ishikawa, RL95-2, HEC1A, KLE) for 15 minutes to 8 days. BCH significantly inhibited cellular leucine uptake; it suppressed cell growth and spheroid formation while reducing mTORC1 signaling pathway activation[5]. BCH (0.3–50mM) treated KB human oral epidermoid carcinoma cells, Saos2 human osteosarcoma cells, and C6 rat glioma cells for 0–3 days. BCH significantly inhibited cell growth and induced DNA fragmentation, apoptosis, and activation of caspase-3/7[6].
In vivo, BCH (240mg/kg) was intraperitoneally injected into HFD/STZ-induced T2DM and db/db mouse models for one week. BCH alleviated diabetic neuropathic pain symptoms[7]. BCH (200mg/kg) was intravenously injected into BALB/c nude mice inoculated with HuCCT1 cholangiocarcinoma cells for 14 days. BCH significantly suppressed tumor growth and enhanced the therapeutic efficacy of gemcitabine and 5-FU[8].
References:
[1] Ohshima Y, Kaira K, Yamaguchi A, et al. Efficacy of system l amino acid transporter 1 inhibition as a therapeutic target in esophageal squamous cell carcinoma. Cancer Sci. 2016 Oct;107(10):1499-1505.
[2] Singh N, Scalise M, Galluccio M, et al. Discovery of Potent Inhibitors for the Large Neutral Amino Acid Transporter 1 (LAT1) by Structure-Based Methods. Int J Mol Sci. 2018 Dec 21;20(1):27.
[3] Wang Q, Holst J. L-type amino acid transport and cancer: targeting the mTORC1 pathway to inhibit neoplasia. Am J Cancer Res. 2015 Mar 15;5(4):1281-94.
[4] Lee Y, Jin C, Ohgaki R, et al. Structural basis of anticancer drug recognition and amino acid transport by LAT1. Nat Commun. 2025 Feb 14;16(1):1635.
[5] Marshall AD, van Geldermalsen M, Otte NJ, et al. LAT1 is a putative therapeutic target in endometrioid endometrial carcinoma. Int J Cancer. 2016 Dec 1;139(11):2529-39.
[6] Kim CS, Cho SH, Chun HS, et al. BCH, an inhibitor of system L amino acid transporters, induces apoptosis in cancer cells. Biol Pharm Bull. 2008 Jun;31(6):1096-100.
[7] Zhou ZY, Wang JY, Li ZX, et al. Branched-Chain Amino Acids Deficiency Promotes Diabetic Neuropathic Pain Through Upregulating LAT1 and Inhibiting Kv1.2 Channel. Adv Sci (Weinh). 2024 Sep;11(33):e2402086.
[8] Kaira K, Sunose Y, Ohshima Y, et al. Clinical significance of L-type amino acid transporter 1 expression as a prognostic marker and potential of new targeting therapy in biliary tract cancer. BMC Cancer. 2013 Oct 16;13:482.
BCH (LAT1-IN-1)是一种具有选择性和竞争性的L型氨基酸转运蛋白1（LAT1）抑制剂。BCH通过抑制细胞对氨基酸的摄取和mTOR磷酸化来抑制癌细胞生长并诱导细胞凋亡。BCH可用于食管癌等癌症的相关研究[1-4]。
在体外，BCH（10mM）处理子宫内膜癌细胞系（Ishikawa、RL95-2、HEC1A、KLE）15分钟至8天。BCH显著抑制细胞对亮氨酸的摄取；BCH抑制细胞生长和球体形成，同时降低mTORC1信号通路激活[5]。BCH（0.3–50mM）处理KB人口腔表皮样癌细胞、Saos2人骨肉瘤细胞及C6大鼠胶质瘤细胞0–3天。BCH显著抑制细胞生长，同时诱导DNA片段化、细胞凋亡并激活caspase-3/7[6]。
在体内，BCH（240mg/kg）腹腔注射于HFD/STZ诱导的T2DM和db/db小鼠模型，持续一周。BCH缓解了糖尿病神经性疼痛症状[7]。BCH（200mg/kg）静脉注射于接种了HuCCT1胆管癌细胞的BALB/c裸鼠，持续14天。BCH显著抑制了肿瘤生长，并增加了吉西他滨和5-FU的治疗效果[8]。