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| Targets |
TY-52156 is a selective and competitive antagonist of the sphingosine-1-phosphate receptor 3 (S1P3), with a Ki value of 110 nM determined in S1P3-CHO cells . It displays approximately 30-fold lower affinity for S1P1, S1P2, S1P4, or S1P5 receptors and does not significantly affect 24 different G-protein coupled receptors or three ion channels at concentrations up to 10 μM (<30% inhibition) .
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| ln Vitro |
The rise in S1P3 client dependency in [Ca2+]i is inhibited by TY-52156[1]. Submicromolar potency and a strong reliance on the S1P3 client are displayed by TY-52156 [1]. 10 μM; 10 min) TY-52156.
TY-52156 preferentially inhibits S1P-induced increase in intracellular calcium concentration ([Ca²⁺]i) in S1P3-CHO cells compared to cells expressing other S1P receptor subtypes . It competitively inhibits the dose-dependent [Ca²⁺]i increase elicited by S1P in S1P3-CHO cells with a Ki value of approximately 110 nM . In human coronary artery smooth muscle cells (HCASMCs), TY-52156 inhibits both S1P-induced [Ca²⁺]i increase and Rho activation . At 10 μM, TY-52156 suppresses S1P-induced expansion of multiple human cancer cell lines, including breast cancer MCF-7 cells, lung cancer A549 cells, glioma U251MG cells, and ovarian cancer OVCAR-5 cells . It also blocks S1P-induced expression of Hes1 and reduces the ALDH-positive cell population (cancer stem cell marker), thereby inhibiting S1P-induced breast cancer stem cell expansion . In HUVEC cells, TY-52156 inhibits S1P-induced Ca²⁺ release . Furthermore, TY-52156 relaxes cerebral arteries precontracted with S1P and decreases coronary flow in isolated perfused rat hearts . |
| ln Vivo |
TY-52156 suppresses FTY-720-induced S1P3 receptor-mediated bradycardia in rats when administered as a pretreatment . In a murine lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) model, intraperitoneal injection of TY-52156 (10 mg/kg) one hour before LPS administration effectively attenuates LPS-induced inflammation by suppressing proinflammatory cytokine expression and restores the endothelial barrier by repairing adherens junctions and reducing vascular leakage . S1PR3 inhibition by TY-52156 protects against ARDS via inhibition of the NF-κB pathway and improvement of mitochondrial oxidative phosphorylation . In a mouse xenograft model, chronic continuous injection of TY-52156 for 6 weeks significantly inhibits the tumorigenicity of SphK1-overexpressing ALDH-positive cells .
Following lipid in vivo, TY-52156 (10 mg/kg, 30 mg/kg; sidewall) reduces the S1P3 receptor-induced bradycardia [1]. |
| Enzyme Assay |
TY-52156 receptor binding affinity was determined using competitive binding assays in S1P3-CHO cells. The Ki value of TY-52156 for the S1P3 receptor was calculated to be approximately 110 nM based on its ability to competitively inhibit the dose-dependent [Ca²⁺]i increase elicited by S1P . Selectivity profiling was performed by testing TY-52156 at 10 μM against a panel of 24 different G-protein coupled receptors and three ion channels, where it showed <30% inhibition, indicating high selectivity for S1P3 .
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| Cell Assay |
Western Blot analysis [1]
Cell Types: Chinese Hamster Ovary K1 cells Tested Concentrations: 10 μM Incubation Duration: 10 min Experimental Results: Inhibits S1P-induced p44/p42 MAPK phosphorylation. ) Inhibits S1P-induced p44/p42 MAPK phosphorylation. TY-52156 intracellular calcium mobilization assay: S1P3-CHO cells (Chinese hamster ovary cells stably expressing human S1P3) were loaded with a calcium-sensitive fluorescent dye. Cells were pre-incubated with various concentrations of TY-52156, and the increase in intracellular calcium concentration ([Ca²⁺]i) induced by S1P stimulation was measured using fluorescence spectrometry. TY-52156 competitively inhibited the S1P-induced [Ca²⁺]i increase, and the Ki value was calculated to be approximately 110 nM . In human coronary artery smooth muscle cells (HCASMCs), TY-52156 (at concentrations not specified) was shown to inhibit both S1P-induced [Ca²⁺]i increase and Rho activation . In HUVEC (human umbilical vein endothelial) cells, TY-52156 was used to inhibit S1P-induced Ca²⁺ release . In LPS-stimulated endothelial cell models, TY-52156 treatment (concentration not specified in the abstract) was shown to suppress proinflammatory cytokine expression and restore endothelial barrier function by repairing adherens junctions . Cancer stem cell assays: TY-52156 at approximately 10 μM suppressed S1P-induced expansion of A549, LNCaP, U251MG, and OVCAR-5 cancer cells, blocked S1P-induced Hes1 expression, and reduced the ALDH-positive cell population . |
| Animal Protocol |
Animal/Disease Models: Male SD rat (290–340 g) [1]
Doses: 10 mg/kg, 30 mg/kg Route of Administration: Oral Experimental Results:In vivo oral administration can inhibit S1P3 receptor-induced bradycardia. TY-52156 Rat bradycardia model: In Sprague-Dawley rats, TY-52156 was administered as a pretreatment (dose not specified in the summary) to evaluate its ability to attenuate FTY-720-induced bradycardia, a broad agonist of S1P receptors. Pretreatment with TY-52156 prevented the FTY-720-P-induced increase in [Ca²⁺]i in a dose-dependent manner . Mouse ARDS model: A total of 114 mice were used. Mice were injected intraperitoneally with 2% pentobarbital in PBS (50 mg/kg) for anesthesia. TY-52156 (10 mg/kg) was injected intraperitoneally 1 hour before LPS injection. LPS (1 mg/mL, 5 mg/kg body weight) or PBS (control) was then injected into the trachea via a 20-gauge catheter. Mice were kept in a vertical position for 2 minutes after intratracheal instillation to ensure distribution. Lung tissue, bronchoalveolar lavage fluid (BALF), and serum were collected at 48 hours after LPS administration for analysis . Mouse xenograft model: TY-52156 was administered via chronic continuous injection for 6 weeks at a concentration of 167 mg/mL (exact dosing volume not specified) to evaluate its inhibitory effect on the tumorigenicity of SphK1-overexpressing ALDH-positive cells . |
| ADME/Pharmacokinetics |
TY-52156 is orally bioavailable. In Sprague-Dawley rats, the oral bioavailability of TY-52156 was determined to be approximately 70.9% . TY-52156 is soluble in DMSO (up to 36.43-50 mg/mL depending on the supplier), soluble in ethanol (up to 94.6 mg/mL), and insoluble in water . It is a solid compound with an orange color, and the powder should be stored at -20°C, protected from light .
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| Toxicity/Toxicokinetics |
TY-52156 According to a safety data sheet, TY-52156 is classified as not a hazardous substance or mixture, with no GHS hazard labeling elements required. No specific hazards have been identified. However, the toxicological effects of this product have not been thoroughly studied. It is not listed as a carcinogen by NTP, IARC Monographs, OSHA, or ACGIH. The product is explicitly labeled for research use only, not for human or veterinary use . In the mouse ARDS study, no treatment-related mortality or significant adverse effects were reported at the dose of 10 mg/kg intraperitoneal injection .
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| References | |
| Additional Infomation |
TY-52156 has a molecular weight of 364.27 g/mol and a molecular formula of C₁₈H₁₉Cl₂N₃O . Its purity is typically ≥98% (HPLC) . TY-52156 has been shown to inhibit S1P-induced vascular contraction via S1P3 receptor antagonism, relax cerebral arteries precontracted with S1P, and decrease coronary flow in isolated perfused rat hearts . Research indicates that S1PR3 is a potential therapeutic target for acute respiratory distress syndrome (ARDS), as S1PR3 inhibition by TY-52156 protects against LPS-induced ARDS via suppression of pulmonary inflammation and promotion of the endothelial barrier through inhibition of NF-κB and improvement of mitochondrial oxidative phosphorylation .
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| Molecular Formula |
C18H19CL2N3O
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| Molecular Weight |
364.268962144852
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| Exact Mass |
363.091
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| Elemental Analysis |
C, 59.35; H, 5.26; Cl, 19.46; N, 11.54; O, 4.39
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| CAS # |
934369-14-9
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| PubChem CID |
16046248
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5.592
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
24
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| Complexity |
446
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C(C)(C)C)C(NNC1C=CC(Cl)=CC=1)=NC1C=CC(Cl)=CC=1
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| InChi Key |
XONRRGIRSGNWFP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H19Cl2N3O/c1-18(2,3)16(24)17(21-14-8-4-12(19)5-9-14)23-22-15-10-6-13(20)7-11-15/h4-11,22H,1-3H3,(H,21,23)
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| Chemical Name |
N-(4-chloroanilino)-N'-(4-chlorophenyl)-3,3-dimethyl-2-oxobutanimidamide
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| Synonyms |
TY52156; TY 52156; TY-52,156; TY 52,156; N-(4-chloroanilino)-N'-(4-chlorophenyl)-3,3-dimethyl-2-oxobutanimidamide; TY52156; CHEBI:144947; TY-52156
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~274.52 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.86 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7452 mL | 13.7261 mL | 27.4522 mL | |
| 5 mM | 0.5490 mL | 2.7452 mL | 5.4904 mL | |
| 10 mM | 0.2745 mL | 1.3726 mL | 2.7452 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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