BLT-1 is a selective scavenger receptor B, type 1 (SR-BI) inhibitor that inhibits DiI-labeled high-density lipoprotein (HDL) uptake with an IC50 value of 0.021μM [1]. BLT-1 blocks lipid transport, including selective uptake and efflux, to prevent SR-BI-mediated cholesterol efflux from cells to HDL[2]. BLT-1 has been widely used to prevent hepatitis C virus (HCV) infection of cells and enhance viral clearance [3].
In vitro, BLT-1 treatment for 3 hours significantly inhibited the proliferation of MCF-7 and MDA-MB-468 cells with the IC50 values of 55nM and 48nM, respectively[4]. Treatment with 10μM BLT-1 for 24 hours in HUVECs enhanced the pro-inflammatory effect induced by sphingosine-1-phosphate (S1P), accompanied by an increase in the protein levels of TNF-α and IL-1β[5]. BLT-1 (10μM) combined with SR-BI siRNA pretreatment for 2 hours on THP-1 macrophages significantly inhibited baicalin-induced cholesterol efflux[6].
In vivo, BLT-1 treatment (25mg/kg/day; p.o.) for 15 days can lead to higher levels of lipid peroxides in the acute myeloid leukemia model of mice, thereby inhibiting the progression of leukemia through ferroptosis[7]. Oral administration of 25mg/kg dose of BLT-1 daily for 4 consecutive weeks inhibited the tumor growth in a PC3 cell-xenograft mouse model, without affecting the body weight [8].
References:
[1] Nieland T J F, Shaw J T, Jaipuri F A, et al. Identification of the molecular target of small molecule inhibitors of HDL receptor SR-BI activity[J]. Biochemistry, 2008, 47(1): 460-472.
[2] Nieland T J F, Penman M, Dori L, et al. Discovery of chemical inhibitors of the selective transfer of lipids mediated by the HDL receptor SR-BI[J]. Proceedings of the national academy of sciences, 2002, 99(24): 15422-15427.
[3] Ohashi H, Koizumi Y, Fukano K, et al. Reply to Padmanabhan and Dixit: Hepatitis C virus entry inhibitors for optimally boosting direct-acting antiviral-based treatments[J]. Proceedings of the National Academy of Sciences, 2017, 114(23): E4527-E4529.
[4] Karimi N, Tehrani F S K. Expression of SR-B1 receptor in breast cancer cell lines, MDAMB-468 and MCF-7: Effect on cell proliferation and apoptosis[J]. Iranian Journal of Basic Medical Sciences, 2021, 24(8): 1069.
[5] Ren K, Lu Y J, Mo Z C, et al. ApoA-I/SR-BI modulates S1P/S1PR2-mediated inflammation through the PI3K/Akt signaling pathway in HUVECs[J]. Journal of physiology and biochemistry, 2017, 73(2): 287-296.
[6] Yu R, Lv Y, Wang J, et al. Baicalin promotes cholesterol efflux by regulating the expression of SR-BI in macrophages[J]. Experimental and Therapeutic Medicine, 2016, 12(6): 4113-4120.
[7] Shi J, Cheng Y, Wang L, et al. SR-B1 deficiency suppresses progression in acute myeloid leukemia via ferroptosis and reverses resistance to venetoclax[J]. Free Radical Biology and Medicine, 2025, 233: 24-38.
[8] Gordon J A, Noble J W, Midha A, et al. Upregulation of scavenger receptor B1 is required for steroidogenic and nonsteroidogenic cholesterol metabolism in prostate cancer[J]. Cancer research, 2019, 79(13): 3320-3331.
BLT-1是一种选择性的清道夫受体B类I型（SR-BI）抑制剂，可抑制DiI标记的高密度脂蛋白（HDL）摄取，IC50值为0.021μM[1]。BLT-1阻断脂质转运，包括选择性摄取和外排，从而阻止SR-BI介导的胆固醇从细胞外流至HDL[2]。BLT-1已被广泛用于预防丙型肝炎病毒（HCV）感染细胞并增强病毒清除[3]。
在体外，BLT-1处理3小时显著抑制了MCF-7和MDA-MB-468细胞的增殖，IC50值分别为55nM和48nM[4]。在HUVEC细胞中使用10μM的BLT-1处理24小时，增强了1-磷酸鞘氨醇（S1P）诱导的促炎效应，并伴有TNF-α和IL-1β蛋白水平的升高[5]。BLT-1（10μM）联合SR-BI siRNA预处理THP-1巨噬细胞2小时，显著抑制了baicalin诱导的胆固醇外流[6]。
在体内，每日口服给予BLT-1（25mg/kg），持续15天，可导致小鼠急性髓系白血病模型中脂质过氧化物水平升高，从而通过铁死亡抑制白血病的进展[7]。连续4周每日口服25mg/kg剂量的BLT-1，抑制了PC3细胞异种移植小鼠模型中的肿瘤生长，且未影响体重[8]。