(R)-Lisofylline is a small molecule compound with anti-inflammatory properties, acting as a lysophosphatidic acid acyltransferase inhibitor (IC₅₀ = 0.6µM)[1]. (R)-Lisofylline interrupts IL-12 signaling-mediated STAT4 activation and reduces the production of unsaturated phosphatidic acid species[2]. (R)-Lisofylline can be used in research on type 1 diabetes and autoimmune diseases[3], and has been shown to ameliorate experimental allergic encephalomyelitis[4].
In vitro, treatment of p53-mutant human ovarian cancer cells (SKOV3, SKOV3 CDDP-resistant, OVCAR3, and OVCAR432) with (R)-Lisofylline (20–100µM) in combination with Cisplatin (CDDP; 10-60µM) for 5 days significantly enhanced the cytotoxic effects of CDDP[5].
In vivo, administration of (R)-Lisofylline (50mg/kg) via intraperitoneal injection for three consecutive weeks in high-fat diet-induced obese C57BL/6 mice significantly improved obesity-related metabolic disorders and cardiac inflammation[6]. (R)-Lisofylline (25mg/kg, twice daily intraperitoneal injection) for two weeks in multiple low-dose streptozotocin-induced C57BL/6J mice significantly reduced the incidence of diabetes[7].
References:
[1] Hybertson BM, Bursten SL, Leff JA, et al. Lisofylline prevents leak, but not neutrophil accumulation, in lungs of rats given IL-1 intratracheally. J Appl Physiol (1985). 1997 Jan;82(1):226-32.
[2] Wyska E, Świerczek A, Pociecha K, et al. Physiologically based modeling of lisofylline pharmacokinetics following intravenous administration in mice. Eur J Drug Metab Pharmacokinet. 2016 Aug;41(4):403-12.
[3] Cui P, Macdonald TL, Chen M, et al. Synthesis and biological evaluation of lisofylline (LSF) analogs as a potential treatment for Type 1 diabetes. Bioorg Med Chem Lett. 2006 Jul 1;16(13):3401-5.
[4] Bright JJ, Sriram S. Immunotherapy of inflammatory demyelinating diseases of the central nervous system. Immunol Res. 2001;23(2-3):245-52.
[5] Husain A, Rosales N, Schwartz GK, et al. Lisofylline sensitizes p53 mutant human ovarian carcinoma cells to the cytotoxic effects of cis-diamminedichloroplatinum (II). Gynecol Oncol. 1998 Jul;70(1):17-22.
[6] Ali M, Bakr MH, Abdelzaher LA, et al. Lisofylline mitigates cardiac inflammation in a mouse model of obesity through improving insulin secretion and activating cardiac AMPK signaling pathway. Cytokine. 2021 Feb;138:155398.
[7] Yang Z, Chen M, Fialkow LB, et al. The novel anti-inflammatory compound, lisofylline, prevents diabetes in multiple low-dose streptozotocin-treated mice. Pancreas. 2003 May;26(4):e99-104.
(R)-Lisofylline一种具有抗炎特性的小分子化合物，作为一种溶血磷脂酸酰基转移酶抑制剂（IC₅₀=0.6µM）[1]。(R)-Lisofylline能够中断IL-12信号介导的STAT4激活，并减少不饱和磷脂酸物质的产生[2]。(R)-Lisofylline可用于1型糖尿病和自身免疫性疾病的研究[3]。(R)-Lisofylline表现出改善过敏性脑脊髓炎的功能[4]。
在体外，(R)-Lisofylline(20–100µM)与顺铂（CDDP；10-60µM）联合处理p53突变的人卵巢癌细胞（SKOV3、SKOV3 CDDP耐药株、OVCAR3和OVCAR432）5天，可显著增强顺铂的细胞毒性作用[5]。
在体内，(R)-Lisofylline（50mg/kg）连续三周腹腔注射处理高脂饮食诱导的肥胖C57BL/6小鼠，显著改善了肥胖引起的代谢紊乱和心脏炎症[6]。(R)-Lisofylline（25mg/kg，每日两次腹腔注射）连续两周处理多次低剂量链脲佐菌素诱导的C57BL/6J小鼠，显著降低了糖尿病发病率[7]。