TCPOBOP is a constitutive androgen receptor (CAR) agonist (EC50=0.05µM) that induces hepatocyte proliferation and hepatomegaly in mice without causing liver damage[1, 2]. Constitutive androgen receptor (CAR) is a nuclear receptor that regulates not only drug-metabolizing enzymes but also energy metabolism[3]. TCPOBOP can attenuate Fas-induced liver injury in mice by altering Bcl-2 protein[4]. TCPOBOP can cause non-target lipid metabolism disorders and increase serum and hepatic triglyceride levels in humanized mice[5].
In vivo, oral administration of TCPOBOP (3mg/kg) to wild-type, EGFRi, and MET KO mice induced hepatocyte proliferation and hepatomegaly, and significantly increased the liver-to-body weight ratio (LW/BW)[6].
References:
[1] Gao Y, Cai C, Zheng W, et al. The slow elimination of 1, 4-bis [2-(3, 5-dichloropyridyloxy)] benzene in mice leads to prolonged constitutive androstane receptor activation and hepatomegaly[J]. Drug Metabolism and Disposition, 2025, 53(6): 100092.
[2] Repo S, Jyrkkarinne J, Pulkkinen J T, et al. Ligand specificity of constitutive androstane receptor as probed by induced-fit docking and mutagenesis[J]. Journal of medicinal chemistry, 2008, 51(22): 7119-7131.
[3] Xu P, Hong F, Wang J, et al. The CAR agonist TCPOBOP inhibits lipogenesis and promotes fibrosis in the mammary gland of adolescent female mice[J]. Toxicology Letters, 2018, 290: 29-35.
[4] Baskin-Bey E S, Huang W, Ishimura N, et al. Constitutive androstane receptor (CAR) ligand, TCPOBOP, attenuates Fas-induced murine liver injury by altering Bcl-2 proteins[J]. Hepatology, 2006, 44(1): 252-262.
[5] Skoda J, Dohnalova K, Chalupsky K, et al. Off-target lipid metabolism disruption by the mouse constitutive androstane receptor ligand TCPOBOP in humanized mice[J]. Biochemical Pharmacology, 2022, 197: 114905.
[6] Bhushan B, Stoops J W, Mars W M, et al. TCPOBOP‐induced hepatomegaly and hepatocyte proliferation are attenuated by combined disruption of MET and EGFR signaling[J]. Hepatology, 2019, 69(4): 1702-1718.
TCPOBOP是一种构成性雄酮受体（CAR）激动剂（EC50=0.05µM），能够小鼠诱导肝细胞增殖和肝肿大，但不会造成肝损伤[1, 2]。构成性雄酮受体（CAR）是一种核受体，不仅调控药物代谢酶，还影响能量代谢[3]。TCPOBOP能够通过改变Bcl-2蛋白减弱Fas诱导的小鼠肝损伤[4]。TCPOBOP在人源化小鼠中能够引起非靶向脂质代谢紊乱，升高血清和肝脏甘油三酯水平[5]。
在体内，TCPOBOP（3mg/kg）通过口服处理野生型、EGFRi、MET KO小鼠，诱导了小鼠肝细胞增生和肝肿大，显著增加了肝体重比（LW/BW）[6]。