GYY 4137 morpholine salt (GYY-4137; GYY4137; ZYJ1122; ZYJ-1122) is a novel, water-soluble and slow releasing Hydrogen sulfide (H2S) donor. It has a variety of pharmacological properties such as anticancer, anti-oxidant, and antihypertensive effects. It can protect against myocardial ischemia and reperfusion injury by attenuating oxidative stress and apoptosis in rats, and inhibit the inflammatory response by suppressing the activation of nuclear factor-kappa B and mitogen-activated protein kinases in Coxsackie virus B3-infected rat cardiomyocytes.
Physicochemical Properties
| Molecular Formula | C15H25N2O3PS2 |
| Molecular Weight | 376.47 |
| Exact Mass | 376.104 |
| CAS # | 106740-09-4 |
| PubChem CID | 46937261 |
| Appearance | White to off-white solid powder |
| Melting Point | 164-166 ºC |
| LogP | 2.246 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 23 |
| Complexity | 324 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | YZMHNNLDUWRZFW-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C11H16NO2PS2.C4H9NO/c1-13-10-2-4-11(5-3-10)15(16,17)12-6-8-14-9-7-12;1-3-6-4-2-5-1/h2-5H,6-9H2,1H3,(H,16,17);5H,1-4H2 |
| Chemical Name | (4-methoxyphenyl)-morpholin-4-yl-sulfanyl-sulfanylidene-λ5-phosphane;morpholine |
| Synonyms | GYY 4137 morpholine salt GYY-4137GYY4137ZYJ1122 ZYJ-1122 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | GYY4137 (400-800 μM) kills seven distinct human cancer cell lines (HeLa, HCT-116, Hep G2, HL-60, MCF-7, MV4-11, and U2OS) in a concentration-dependent manner, while it has no effect on the survival of human lung fibroblasts that are normal cells (IMR90, WI-38) [2]. In human synoviocytes (HFLS) and articular chondrocytes (HAC), GYY4137 (0.1-0.5 mM) decreases LPS-induced production of nitrite (NO2), PGE2, TNF-α, and IL-6. It also decreases inducible nitric acid salt levels and catalytic activity of oxidative oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as LPS-induced NF-κB activation [3]. |
| ln Vivo | In two animal models, GYY4137 (100–300 mg/kg; intraperitoneal injection; once daily for 14 days) significantly and dose-dependently decreased the volume of tumors [2]. ?GYY4137 (50 mg/kg, i.p.) was injected one hour prior to complete Freund's adjuvant (CFA) treatment in mice. This resulted in an increase in knee joint swelling as well as anti-inflammatory effects, as demonstrated by the decrease in (MPO) and N. Acetyl-β-D-glucosaminidase (NAG) activity was considerably decreased and TNF-α, IL-1β, IL-6, and IL-8 concentrations were decreased when GYY4137 was administered six hours after CFA [3]. ?In the subcutaneous HepG2 xenograft model, GYY4137 effectively suppresses tumor development by blocking both STAT3 activation and the expression of its target gene [4]. ?GYY4137 inhibits α-synuclein nitration and nitrative stress in the MPTP animal model of Parkinson's disease [5]. |
| Cell Assay |
Cell Viability Assay[2] Cell Types: HeLa, HCT-116, Hep G2, HL-60, MCF-7, MV4-11 and U2OS Tested Concentrations: 400 or 800 µM Incubation Duration: 5 days Experimental Results: Dramatically affected cancer cells survivability. |
| Animal Protocol |
Animal/Disease Models: Female, severe combined immunodeficiency (SCID) mice (carrying HL-60 or MV4-11 cells) [2] Doses: 100, 200 and 300 mg/kg Route of Administration: intraperitoneal (ip) injection; one time/day for 14 Day Experimental Results: The tumor volume of animals injected with HL-60 and MV4-11 was diminished by 52.5±9.2% and 55.3±5.7%. |
| References |
[1]. Characterization of a novel, water-soluble hydrogen sulfide-releasing molecule (GYY4137): new insights into the biology of hydrogen sulfide. Circulation. 2008;117(18):2351-2360. [2]. The slow-releasing hydrogen sulfide donor, GYY4137, exhibits novel anti-cancer effects in vitro and in vivo. PLoS One. 2011;6(6):e21077. [3]. The complex effects of the slow-releasing hydrogen sulfide donor GYY4137 in a model of acute joint inflammation and in human cartilage cells. J Cell Mol Med. 2013;17(3):365-376. [4]. GYY4137, a hydrogen sulfide (H₂S) donor, shows potent anti-hepatocellular carcinoma activity through blocking the STAT3 pathway. Int J Oncol. 2014;44(4):1259-1267. [5]. GYY4137, an H2S Slow-Releasing Donor, Prevents Nitrative Stress and α-Synuclein Nitration in an MPTP Mouse Model of Parkinson's Disease. Front Pharmacol. 2017;8:741. Published 2017 Oct 30. |
| Additional Infomation | Morpholine (4-methoxyphenyl)(morpholino)phosphinodithioate is an organic molecular entity. |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~265.63 mM) H2O : ~19.23 mg/mL (~51.08 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.64 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.64 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 50 mg/mL (132.81 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6563 mL | 13.2813 mL | 26.5625 mL | |
| 5 mM | 0.5313 mL | 2.6563 mL | 5.3125 mL | |
| 10 mM | 0.2656 mL | 1.3281 mL | 2.6563 mL |