GYY 4137 morpholine salt is a novel slow-release hydrogen sulfide (H2S) donor with vasodilatory, antihypertensive, anti-inflammatory, and anticancer activities[1, 2]. This product is provided in the form of GYY 4137 morpholine salt.
In vitro, GYY 4137 morpholine salt (0–400 μM) was used to treat liver cancer cells (HepG2 and Bel7402 cells) for 24-72 hours. It inhibited cell viability in a time- and dose-dependent manner, caused cell cycle arrest, and induced apoptosis. It also inhibited IL-6-induced STAT3 phosphorylation and hypoxia-induced expression of VEGF and HIF-1α[3]. GYY 4137 morpholine salt (500 μM) treated CBS-deficient cell lines GES1 and HFE145 for 24 hours, significantly reducing the activity of the inflammatory factor NF-κB within the cells[4].
In vivo, GYY 4137 morpholine salt (100, 200, and 300 mg/kg/day; i.p.) was administered to HL-60 and MV4-11 cell xenograft mice for 14 days, resulting in a dose-dependent reduction in tumor volume. At the highest dose, tumor volume was reduced by 52.5±9.2% and 55.3±5.7% in the respective models[5]. GYY 4137 morpholine salt (50 mg/kg; i.p.) significantly improved motor deficits and reduced the loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra and the decrease in TH expression in the striatum in a Parkinson's disease mouse model[6]. GYY 4137 morpholine salt (50 mg/kg; i.p.) administered to mice with acute arthritis 18 hours after complete Freund's adjuvant (CFA) significantly reduced knee swelling and decreased synovial myeloperoxidase (MPO) activity[7].
References:
[1] Rose P, Dymock B W, Moore P K. GYY4137, a novel water-soluble, H2S-releasing molecule[J]. Methods in enzymology, 2015, 554: 143-167.
[2] Nin D S, Idres S B, Song Z J, et al. Biological effects of morpholin-4-Ium 4 methoxyphenyl (morpholino) phosphinodithioate and other phosphorothioate-based hydrogen sulfide donors[J]. Antioxidants & redox signaling, 2020, 32(2): 145-158.
[3] Lu S, Gao Y, Huang X, et al. GYY4137, a hydrogen sulfide (H2S) donor, shows potent anti-hepatocellular carcinoma activity through blocking the STAT3 pathway[J]. International journal of oncology, 2014, 44(4): 1259-1267.
[4] Padmanabhan N, Kyon H K, Boot A, et al. Highly recurrent CBS epimutations in gastric cancer CpG island methylator phenotypes and inflammation[J]. Genome biology, December 2021.
[5] Lee Z W, Zhou J, Chen C S, et al. The slow-releasing hydrogen sulfide donor, GYY4137, exhibits novel anti-cancer effects in vitro and in vivo[J]. PloS one, 2011, 6(6): e21077.
[6] Hou X, Yuan Y, Sheng Y, et al. GYY4137, an H2S slow-releasing donor, prevents nitrative stress and α-synuclein nitration in an MPTP mouse model of Parkinson’s disease[J]. Frontiers in Pharmacology, 2017, 8: 741.
[7] Li L, Fox B, Keeble J, et al. The complex effects of the slow‐releasing hydrogen sulfide donor GYY 4137 in a model of acute joint inflammation and in human cartilage cells[J]. Journal of cellular and molecular medicine, 2013, 17(3): 365-376.
GYY 4137 morpholine salt是一种新型缓释硫化氢（H2S）供体，具有血管扩张、抗高血压、抗炎和抗癌活性[1, 2]。本产品以GYY 4137吗啉盐的形式提供。
在体外，GYY 4137 morpholine salt （0–400μM）处理肝癌细胞（HepG2和Bel7402细胞）24-72h，以时间和剂量依赖性的方式抑制了细胞活力，导致细胞周期停滞并诱导凋亡，还抑制了IL-6诱导的STAT3磷酸化以及缺氧诱导的VEGF和HIF-1α的表达[3]。GYY 4137 morpholine salt （500μM）处理GES1和 HFE145 胱硫醚 β-合酶（CBS）缺陷细胞系24h，显著降低了细胞内炎症因子NF-κB的活性[4]。
在体内，GYY 4137 morpholine salt（100, 200, and 300 mg/kg/day; i.p.）治疗HL-60和MV4-11细胞异种移植小鼠14天，剂量依赖性地减少了两种模型中的肿瘤体积，在最高剂量给药下，肿瘤体积分别减少了52.5±9.2%和55.3±5.7%[5]。GYY 4137 morpholine salt（50mg/kg；i.p.）治疗帕金森模型小鼠，显著改善了运动障碍，减轻了黑质中酪氨酸羟化酶（TH）阳性神经元的损失和纹状体中TH表达的减少[6]。GYY 4137 morpholine salt（50 mg/kg；i.p.）在完全弗氏佐剂（CFA）后18小时治疗急性关节炎小鼠，减少了膝关节肿胀，降低了滑液髓过氧化物酶（MPO）活性[7]。