NSC 90469

NSC 90469 (3,5-Diiodo-L-thyronine) is an orally active thyroid hormone derivative. NSC 90469 inhibits JNK phosphorylation and NF-κB acetylation, blocks SIRT1 protein expression, induces elevated PGC-1α levels, and stimulates COX activity. NSC 90469 enhances UCP1-mediated thermogenesis, increases hepatic Dio1 activity, inhibits TSH levels and hypothalamic-pituitary-thyroid axis function, enhances lipid metabolism, and regulates energy metabolism via the mitochondrial pathway. NSC 90469 prevents blood glucose reduction, reduces urinary albumin excretion, inhibits renal matrix expansion, decreases TGF-β1 expression, and reduces renal fibronectin and type Ⅳ collagen deposition. NSC 90469 also increases energy expenditure and prevents diet-induced overweight. NSC 90469 can be used in studies related to diabetic nephropathy, hypothyroidism, non-alcoholic fatty liver disease, and diet-induced obesity^{[1][2][3][4][5]}. In Vitro:NSC 90469 (T2) (100 μM; 1-24 h) attenuates high glucose-induced profibrotic changes, restores the expression and activity of SIRT1, and inhibits the acetylation of NF-κB and phosphorylation of JNK in rat glomerular mesangial cells^[1].
NSC 90469 (10^-12-10^-6 M; 30 min) dose-dependently stimulates cytochrome oxidase activity in brown adipose tissue homogenates from hypothyroid rats, with a half-maximal effective concentration of 10^-11 M and a maximal activating concentration of 10^-8 M^[2].
NSC 90469 (0.1 nM-10000 nM; 24 h) exhibits differential thyroid-mimetic activity in GH3 cells, stimulates GH mRNA expression, and downregulates TRβ2 mRNA expression^[3].
NSC 90469 (10^-5 M) reduces lipid overload in primary rat hepatocytes exposed to Oleic acid (HY-N1446)/Palmitic acid (HY-N0830) by recruiting adipose triglyceride lipase (ATGL), stimulating mitochondrial function, and regulating the expression of lipid-related proteins^[4].
NSC 90469 (10^-7-10^-5 M; 24 h) reduces lipid accumulation and stimulates mitochondrial uncoupling in FAO rat hepatocellular carcinoma cells exposed to Oleic acid (HY-N1446)/Palmitic acid (HY-N0830) via a non-receptor-mediated mechanism^[4].
NSC 90469 inhibits lipid synthesis in HepG2 cells by activating multiple kinase pathways to block the proteolytic cleavage of SREBP-1^[4].
NSC 90469 rapidly modulates intracellular Ca²⁺ and NO levels in pituitary GH3 cells, and activates the mitochondrial Na⁺/Ca²⁺ exchanger through the interaction between the plasma membrane and mitochondria^[4].
NSC 90469 (0.3 nM; 5 min) stimulates mitochondrial respiration in isolated liver and muscle of goldfish Carassius auratus^[4]. In Vivo:NSC 90469 (0.25 mg/kg, i.p., once daily for 12 weeks) ameliorates streptozotocin (HY-13753)-induced diabetic nephropathy in male Sprague-Dawley rats, reduces blood glucose to 6.3 mM, decreases the urinary albumin/creatinine ratio to 68.4 μg/mg, and restores the activity and expression of renal SIRT1^[1].
NSC 90469 (3,5-diiodo-L-thyronine) (250 μg/kg, i.p.; once daily for 1 week) increases resting energy expenditure by 13% in hypothyroid Wistar rats. It activates brown adipose tissue thermogenesis by enhancing mitochondrial function, sympathetic innervation and angiogenesis, while promoting the multilocular brown adipocyte phenotype, without affecting serum T₃/T₄ levels^[2].
NSC 90469 (100 µg/kg, i.p.; single administration) enhances cold tolerance, increases energy expenditure, and prolongs survival time in hypothyroid rats exposed to low-temperature environments^[4].
NSC 90469 (250 µg/kg; daily administration; for 4 consecutive weeks) prevents high-fat diet (HFD)-induced obesity, hepatic lipid accumulation, hyperlipidemia and insulin resistance in rats without inducing thyrotoxicosis^[4].
NSC 90469 (1.25 mg/100 g body weight; p.o.; daily) reduces total cholesterol and low-density lipoprotein (LDL) cholesterol by 70% in Western diet-fed Ldlr knockout mice^[4].