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。
Cas No.:76150-91-9
Sample solution is provided at 25 µL, 10mM.
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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]。
| Animal experiment [1]: | |
Animal models | METfl/fl: Tam-Cre+/+ mice with a targeted deletion for exon 16 with MET KO |
Preparation Method | Mice were injected i.p. for five consecutive days with tamoxifen to obtain MET KO mice. Control group consisted of littermates injected with vehicle (corn oil) only. Single dose of TCPOBOP (3mg/kg; prepared in corn oil) was administered by oral gavage at least 5 days after last tamoxifen injection. For EGFR inhibition, Canertinib, an EGFR inhibitor (EGFRi) was administered to mice in diet at 80mg/kg/day. Canertinib diet was initiated one day prior to TCPOBOP injection. For combined inhibition of MET and EGFR [MET KO+EGFRi], Canertinib diet was administered to MET KO mice at least 4 days after tamoxifen injection. For initial studies, mice from control, EGFRi, MET KO and [MET KO+EGFRi] groups were sacrificed at 48h after TCPOBOP administration. For timecourse analysis, mice from control and [MET KO+EGFRi] group were euthanized at various time points (0, 1, 2, 5 and 10 days) after TCPOBOP administration. |
Dosage form | 3mg/kg; p.o. |
Applications | TCPOBOP treated control mice showed remarkable (1.6 fold vs no TCPOBOP control) increase in liver to body weight (LW/BW) ratio at 48h. EGFRi mice had similar increase and MET KO displayed slightly lower increase, but not significantly different compared to control. |
References: | |
| Cas No. | 76150-91-9 | SDF | |
| 化学名 | 1,4-bis((3,5-dichloropyridin-2-yl)oxy)benzene | ||
| Canonical SMILES | ClC1=CC(Cl)=CN=C1OC(C=C2)=CC=C2OC(C(Cl)=C3)=NC=C3Cl | ||
| 分子式 | C16H8Cl4N2O2 | 分子量 | 402.06 |
| 溶解度 | DMF: 3 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4872 mL | 12.436 mL | 24.8719 mL |
| 5 mM | 497.4 μL | 2.4872 mL | 4.9744 mL |
| 10 mM | 248.7 μL | 1.2436 mL | 2.4872 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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