hepatic disease

Moexipril hydrochloride (Moexipril HCl) 是一种有口服活性的，不含巯基的血管紧张素转化酶抑制剂，可治疗高血压和充血性心力衰竭。

Palmatine chloride 是口服具有活力的不可逆 IDO-1抑制剂。它能够减轻结肠损伤，预防肠道菌群失调和调节色氨酸分解代谢，并改善 DSS 诱发的结肠炎。

Simvastatin (MK 733) 是一种 HMG-CoA 还原酶抑制剂 (Ki=0.2 nM)，具有口服活性。Simvastatin 具有降血脂活性，可以抑制肝脏产生胆固醇，还可以用于预防心血管疾病。

Torsemide (AC-4464) 是具有口服活性的亨氏环利尿剂，也具有抗醛固酮和血管舒张活性。它可用于研究心力衰竭、肾脏疾病、肝硬化。

Berberine (Umbellatine) 属于生物碱类天然产物，可以激活 AMPK、抑制 DNA 拓扑异构酶、诱导 ROS 生成。Berberine 具有抗肿瘤、抗菌、降血糖、降血脂等生物学活性。

Palmatine (Burasaine) 是口服具有活力的、不可逆IDO-1抑制剂。它可以减轻结肠损伤，预防肠道菌群失调和调节色氨酸分解代谢，从而改善DSS (Dextran Sulphate Sodium Salt) 诱发的结肠炎。它有用于结肠炎的研究潜力。

Istradefylline (KW-6002) 是选择性的可口服的腺苷 A2A 受体拮抗剂，可用于研究药物滥用、睡眠障碍、肝损伤、帕金森病和不安腿综合征等的治疗和基础科学的试验。

Larsucosterol ammonium salt(拉舒胆醇铵盐)是Larsucosterol(DUR-928)的盐形式和25HC3S的衍生物。Larsucosterol是一种DNA甲基转移酶抑制剂(DNMT)，是一种有效的肝 X 受体 (LXR) 拮抗剂，一种内源性硫酸氧甾醇和一种表观遗传调节剂，能够调节脂质代谢，减少炎症，治疗肝病。

PTUPB 是强效的sEH(IC50:0.9 μM)和COX-2(IC50:1.26 μM)的双向抑制剂。

LP-533401 hydrochloride 是不能穿过血脑屏障的外周 Tph 抑制剂，抑制5-羟色胺合成，可用于研究牙周病和肝脂肪变性。

ZLY06 是一种口服活性的双重 PPAR δ 和 γ 激动剂（PPAR δ: EC50=341 nM；PPAR γ: EC50=237 nM），有效抑制 AKT1 的磷酸化并促进 CD36 的上调，从而诱导肝脏脂质蓄积。此外，ZLY06 在不增加体重的前提下，能显著改善糖脂代谢，主要通过促进脂肪酸的 β 氧化以及抑制肝脏脂肪生成，从而减轻脂肪肝。

SET-171 是一种 JNK (c-JunN-terminal kinase) 抑制剂，通过抑制肝脏丙酮酸激酶 (PKL) 的表达，展现出显著的抗癌特性和调节脂质代谢的潜力。在抗肿瘤研究中，SET-171 对人肝癌细胞系 HepG2 和 Huh7 的 IC50 值分别为 8.82 μM 和 2.97 μM，显示出较高的细胞毒性。此外，在非酒精性脂肪性肝病 (NAFLD) 的研究中，SET-171 显著降低三酰甘油 (TAG) 水平，并抑制与脂肪变性相关蛋白的表达。SET-171 有望用于肝细胞癌 (HCC) 和非酒精性脂肪性肝病的研究。

Quinuronium sulfate is a drug used to treat Babesia divergens infections in calves. It did not prevent treated animals from being disease carriers. It may also cause hepatic centrilobular fatty degeneration, but no depletion of hepatic glutathione (GSH).

Ajoene is a disulfide that has been found inA. sativumand has diverse biological activities, including antibacterial, anticancer, antiplatelet, and antioxidant properties.1,2,3,4It is active against Gram-positive (MICs = 5-160 µg ml) and Gram-negative bacteria (MICs = 136-200 µg ml), as well as yeasts (MICs = 10-20 µg ml).1Ajoene is cytotoxic to mouse melanoma cells (IC50= 18 µM), as well as human colon, lung, mammary, and pancreatic cancer cells (IC50s = 7-41 µM).2It reduces tumor growth in a B16 BL6 mouse model of melanoma when administered at a dose of 25 mg kg every other day and decreases the number of lung metastases when administered prior to tumor cell inoculation at doses ranging from 1-25 mg kg. It inhibits ADP- or collagen-induced platelet aggregation in isolated baboon platelets when used at concentrations ranging from 75 to 150 µg ml and in platelet-rich plasma isolated from baboons when administered at a dose of 25 mg kg.3Ajoene (25 mg kg) prevents thrombus formation on damaged arterial walls in heparinized pigs in anin situmodel of thrombogenesis.5It also reduces high-fat diet-induced hepatic steatosis, histopathological markers of liver damage, thiobarbituric acid reactive substances (TBARS) formation, and protein oxidation in a mouse model of non-alcoholic fatty liver disease (NAFLD).4 1.Naganawa, R., Iwata, N., Ishikawa, K., et al.Inhibition of microbial growth by ajoene, a sulfur-containing compound derived from garlicAppl. Environ. Microbiol.62(11)4238-4242(1996) 2.Taylor, P., Noriega, R., Farah, C., et al.Ajoene inhibits both primary tumor growth and metastasis of B16 BL6 melanoma cells in C57BL 6 miceCancer Lett.239(2)298-304(2006) 3.Teranishi, K., Apitz-Castro, R., Robson, S.C., et al.Inhibition of baboon platelet aggregation in vitro and in vivo by the garlic derivative, ajoeneXenotransplantation10(4)374-379(2003) 4.Han, C.Y., Ki, S.H., Kim, Y.W., et al.Ajoene, a stable garlic by-product, inhibits high fat diet-induced hepatic steatosis and oxidative injury through LKB1-dependent AMPK activationAntioxid. Redox Signal.14(2)187-202(2011) 5.Apitz-Castro, R., Badimon, J.J., and Badimon, L.A garlic derivative, ajoene, inhibits platelet deposition on severely damaged vessel wall in an in vivo porcine experimental modelThromb. Res.75(3)243-249(1994)

ML-262 是一种高效的肝脂质滴形成抑制剂，可用于研究非酒精性脂肪肝。

ZLY032 is a dual agonist of free fatty acid receptor 1 (FFAR1 GPR40; EC50= 68 nM in a FLIPR assay) and peroxisome proliferator-activated receptor δ (PPARδ; EC50= 102 nM in a reporter assay).1It is selective for FFAR1 and PPARδ over PPARα and PPARγ (EC50s = >10 μM for both). ZLY032 (40 mg kg, twice per day) reduces blood glucose levels in an oral glucose tolerance test and decreases plasma total cholesterol and triglyceride levels in theob obmouse model of metabolic disease.2It reduces hepatic steatosis and plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in a mouse model of non-alcoholic steatohepatitis (NASH) induced by a methionine and choline-deficient diet at the same dose. 1.Li, Z., Chen, Y., Zhou, Z., et al.Discovery of first-in-class thiazole-based dual FFA1 PPARδ agonists as potential anti-diabetic agentsEur. J. Med. Chem.164352-365(2019) 2.Li, Z., Zhou, Z., Hu, L., et al.ZLY032, the first-in-class dual FFA1 PPARδ agonist, improves glucolipid metabolism and alleviates hepatic fibrosisPharmacol Res.159105035(2020)

CX08005 是一种蛋白酪氨酸磷酸酶 1B 抑制剂，可减轻与非酒精性脂肪肝相关的肝脏脂质蓄积和微循环障碍。

Trihydroxycholestanoic acid is an intermediate in the biosynthesis of cholic acid .1 Elevated plasma levels of trihydroxycholestanoic acid have been found in patients with Zellweger syndrome, a neurological disorder characterized by mutations in PEX genes which result in defects in peroxisome formation.2,3 |1. Keane, M.H., Overmars, H., Wikander, T.M., et al. Bile acid treatment alters hepatic disease and bile acid transport in peroxisome-deficient PEX2 Zellweger mice. Hepatology 45(4), 982-997 (2007).|2. Ferdinandusse, S., Overmars, H., Denis, S., et al. Plasma analysis of di- and trihydroxycholestanoic acid diastereoisomers in peroxisomal α-methylacyl-CoA racemase deficiency. J. Lipid Res. 42(1), 137-141 (2001).|3. Klouwer, F.C.C., Berendse, K., Ferdinandusse, S., et al. Zellweger spectrum disorders: Clinical overview and management approach. Orphanet J. Rare Dis. 10, 151 (2015).

Taurohyodeoxycholic acid（牛磺酸去氧胆酸）是一种胆汁酸，在调节肝脏炎症微环境方面发挥着关键作用。THDCA可以减少TNF-α和IL-6的表达并抑制肝细胞癌（HCC）的发展。能够结合黄芪多糖抑制非酒精性脂肪性肝病，调节胆汁酸代谢：通过上调CYP7B1和下调CYP7A1，降低肝脏中CD36的表达，减少肝脏脂质积累。

Inclisiran sodium (ALN-PCSsc sodium) 是一种与三触角 N-乙酰半乳糖胺碳水化合物 （GalNAc） 偶联的双链 siRNA，具有抗高血压活性，抑制 PCSK9 的转录，抑制前蛋白转化酶枯草杆菌蛋白酶-kexin 9 型的肝脏合成， 可用于研究心血管疾病 。

ML261 是肝脂滴形成的抑制剂，IC50值为 69.7 nM。ML261 在非酒精性脂肪性肝病 (NAFLD) 和炎症中具有研究价值。

6(5H)-Phenanthridinone is an inhibitor of poly(ADP-ribose) polymerase 1 (PARP1) and PARP2. It decreases radiation-induced PARP activity and proliferation of RDM4 murine lymphoma cells. 6(5H)-Phenanthridinone reduces NF-κB-induced transcription of the genes encoding TNF-α, IL-2, and IFN-γ in rat lymphocytes. In vivo, 6(5H)-phenanthridinone reduces spinal cord expression of inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, IL-2, and IFN-γ and reduces disease score in a rat model of experimental autoimmune encephalomyelitis (EAE). It also decreases serum levels of lactate dehydrogenase as well as hepatic lipid peroxidation, oxidative DNA damage, and PARP levels.

FXR agonist4，一种法尼酯X受体(FXR)激动剂，具有1.05 μM的EC50值。该化合物在DIO小鼠模型中有效地改善了高脂血症、肝脏脂肪变性、胰岛素抵抗以及肝脏炎症，因此可用于非酒精性脂肪性肝病(NAFLD)的研究。

Subtilisin (EC 3.4.21.14) 是一种从细菌中提取的丝氨酸蛋白酶，可促进肝脏 LDL 受体 （LDLR）降解，可用于研究心血管疾病。