non-alcoholic fatty liver disease (nafld)

Vidofludimus (SC12267) 是一种新型的二氢乳清酸脱氢酶 (DHODH) 小分子抑制剂，可在不影响淋巴细胞增殖的条件下抑制IL-17的分泌。

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。

SKLB102 对PPARγ显示出较强的亲和力。该化合物能够通过调节脂肪细胞因子的表达以及预防胰岛素抵抗，显著减少脂肪沉积，从而有效保护肝脏免受非酒精性脂肪性肝病（NAFLD）的损害。

1-Palmitoyl-2-stearoyl-3-oleoyl-rac-glycerol is a triacylglycerol that contains palmitic , stearic , and oleic acid at the sn-1, sn-2, and sn-3 positions, respectively. It has been detected in RAW 264.7 cells by neutral loss MS. Increased serum levels of 1-palmitoyl-2-stearoyl-3-oleoyl-rac-glycerol are a potential biomarker for non-alcoholic fatty liver disease (NAFLD).

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)

Resolvin E2 (RvE2) is a member of the specialized pro-resolving mediator (SPM) family of bioactive lipids.1It is produced from eicosapentaenoic acidviaan 18-HEPE intermediate, which is formed by aspirin-acetylated COX-2-mediated oxidation of EPA, by 5-lipoxygenase (5-LO) in human polymorphonuclear (PMN) neutrophils.2,3RvE2 (20 ng/animal) inhibits increases in inflammatory exudate neutrophil infiltration in a mouse model of peritonitis induced by zymosan A .3Hepatic RvE2 levels are increased in mice fed normal chow, as well as in a mouse model of high-fat diet-induced non-alcoholic fatty liver disease (NAFLD), by dietary supplementation with EPA.4Plasma levels of RvE2 are increased by dietary supplementation with fish oil containing ω-3 polyunsaturated fatty acids (PUFAs) in patients with peripheral artery disease or chronic kidney disease.1,5,6 1.Chiang, N., and Serhan, C.N.Specialized pro-resolving mediator network: An update on production and actionsEssays Biochem.64(3)443-462(2020) 2.Tjonahen, E., Oh, S.F., Siegelman, J., et al.Resolvin E2: Identification and anti-inflammatory actions: Pivotal role of human 5-lipoxygenase in resolvin E series biosynthesisChemistry & Biology131193-1202(2006) 3.Sungwhan, F.O., Pillai, P.S., Recchiuti, A., et al.Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammationJ. Clin. Invest.121(2)569-581(2011) 4.Echeverría, F., Valenzuela, R., Espinosa, A., et al.Reduction of high-fat diet-induced liver proinflammatory state by eicosapentaenoic acid plus hydroxytyrosol supplementation: Involvement of resolvins RvE1/2 and RvD1/2J. Nutr. Biochem.6335-43(2019) 5.Ramirez, J.L., Gasper, W.J., Khetani, S.A., et al.Fish oil increases specialized pro-resolving lipid mediators in PAD (the OMEGA-PAD II trial)J. Surg. Res.238164-174(2019) 6.Barden, A.E., Shinde, S., Burke, V., et al.The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney diseaseProstaglandins Other Lipid Mediat.1361-8(2018)

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。

AMPK activator 6 (Compound GC) 可降低 HepG2 和 3T3-L1 细胞中的脂质含量并激活AMPK 通路。AMPK activator 6 对血清中甘油三酯 (TG)、总胆固醇 (TC)、低密度脂蛋白-C (LDL-C) 和其他生化指标的增加有显著的抑制作用。AMPK activator 6 在非酒精性脂肪肝（NAFLD）和代谢综合征中有研究价值。

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。

Fazpilodemab (BFKB8488A) 是一种全长人源化双特异性抗体，可选择性靶向并激活 Klotho β 和成纤维细胞生长因子受体 1c 受体复合物，可用于研究非酒精性脂肪性肝病 (NAFLD) 。

Cisd2 agonist 1 是一种高效的 CDGSH 铁硫结构域 2 (CISD2) 激动剂（EC50：34 nM），具有潜在的抗癌活性，可用于研究非酒精性脂肪肝疾病（NAFLD）。

Demethyleneberberine chloride是一种具有线粒体靶向性的天然抗氧化剂，能通过抑制NF-κB通路及调节Th细胞平衡来缓解小鼠结肠炎并抑制炎症。此外，作为一种AMPK激活剂，该化合物亦用于非酒精性脂肪性肝病（NAFLD）的研究。

PF-07238025是一种BCKDC激酶(BDK)抑制剂，具有EC50值为19 nM。它通过稳定BDK和BCKDH复合体中的E2亚基相互作用，阻碍E1亚基的磷酸化过程，从而抑制了BCKDH的活性。由于BDK的磷酸化作用是控制支链氨基酸(BCAA)降解过程中的限速步骤，PF-07238025的作用与包括心力衰竭(HF)、2型糖尿病(T2DM)、非酒精性脂肪肝病(NAFLD)及肥胖在内的多种代谢性疾病的发病机制相关。研究显示PF-07238025能在小鼠体内改善心脏代谢指标并提升葡萄糖耐量。

PF-07247685是一种BCKDC激酶(BDK)抑制剂，具有较强的活性(EC50=2.2 nM)。该化合物能有效稳定BDK与BCKDH E2核心亚基之间的相互作用，并阻断E1亚基的磷酸化过程。BCKDH的活性受到BDK介导的磷酸化调控，从而控制支链氨基酸(BCAA)降解的关键步骤。BCAA的代谢失调与心力衰竭(HF)、2型糖尿病(T2DM)、非酒精性脂肪肝病(NAFLD)及肥胖等多种疾病相关联，尤其在心脏代谢疾病中表现明显。PF-07247685在小鼠模型中对心脏代谢终点产生改善效果，并提升了葡萄糖耐量。

3-Epideoxycholic acid (EDCA), a secondary bile acid and an epimer of deoxycholic acid, serves as a steroidal host compound in the enantioselective purification of (2R,3S)-3-methyl-2-pentanol from its racemates via enclathration. Additionally, decreased fecal levels of EDCA have been observed in pediatric patients with non-alcoholic fatty liver disease (NAFLD).

HSD17B13-IN-11 (Compound 2) 是一种抑制羟基类固醇 17β-脱氢酶 13 (HSD17B13) 的化合物，其IC50值对于白三烯 B3 和雌二醇分别为 ≤ 1 μM和 ≤ 0.1 μM。该化合物主要用于研究肝病、代谢性疾病或心血管疾病，例如非酒精性脂肪肝病 (NAFLD)、非酒精性脂肪性肝炎 (NASH) 或药物性肝损伤 (DILI)。

HSD17B13-IN-59（Compound 177）是一种针对羟基类固醇17β-脱氢酶13（HSD17B13）的抑制剂，展示出优异的抑制活性，其IC50值≤ 0.1 μM。此化合物主要应用于研究肝病、代谢性疾病和心血管疾病，如NAFLD、NASH或药物性肝损伤（DILI）。

HSD17B13-IN-66 (Compound 146)是一种针对羟基类固醇17β-脱氢酶13 (HSD17B13)的抑制剂，其IC50值对雌二醇为≤0.1 μM。该化合物广泛应用于研究包括非酒精性脂肪性肝病 (NAFLD)、非酒精性脂肪肝炎 (NASH)、药物性肝损伤 (DILI) 在内的肝病以及代谢性和心血管疾病。

HSD17B13-IN-79 (Compound 32) 为一种羟基类固醇 17β-脱氢酶 13 (HSD17B13) 抑制剂，其IC50值对于雌二醇 ≤ 0.1 μM。该化合物适用于研究肝病、代谢性疾病或心血管疾病，例如 NAFLD 或 NASH，以及药物性肝损伤 (DILI)。

HSD17B13-IN-81 (Compound 154) 作为一种有效的羟基类固醇 17β-脱氢酶 13 (HSD17B13)抑制剂，具有 ≤ 0.1 μM 的雌二醇 IC50 值。该化合物主要被用于研究包括非酒精性脂肪肝病 (NAFLD)、非酒精性脂肪肝炎 (NASH) 在内的肝病，以及代谢性和心血管疾病，或药物性肝损伤 (DILI)。

PXL770是一种直接AMP激酶激活剂，可用于非酒精性脂肪肝病（NAFLD）的研究。

YGT-31作为PPARγ调节剂,其IC50值为1.72 μM,Ki值为0.62 μM.通过抑制CDK5介导的PPARγ-Ser273的磷酸化,YGT-31能在db db小鼠的2型糖尿病模型中显著降低血糖并改善胰岛素抵抗.此外,YGT-31在小鼠的非酒精性脂肪性肝病(NAFLD)模型中也展示了抗肝脂肪变性的效果.

HSD17B13-IN-103 (Compound 44) 作为HSD17B13的抑制剂,主要用于非酒精性脂肪性肝病 (NAFLD) 及非酒精性脂肪性肝炎 (NASH) 的相关研究.

GprA为新合成的GPR120 FFAR4激动剂,具有针对人类GPR120全长同工型的AC50值为203 nM.该化合物主要应用于非酒精性脂肪性肝病(NAFLD)的研究领域.