LDN-27219Tgases inhibitor CAS# 312946-37-5 |
Quality Control & MSDS
3D structure
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| Cas No. | 312946-37-5 | SDF | Download SDF |
| PubChem ID | 1150683 | Appearance | Powder |
| Formula | C20H16N4O2S2 | M.Wt | 408.5 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 125 mg/mL (306.00 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 2-(4-oxo-3,5-diphenylthieno[2,3-d]pyrimidin-2-yl)sulfanylacetohydrazide | ||
| SMILES | C1=CC=C(C=C1)C2=CSC3=C2C(=O)N(C(=N3)SCC(=O)NN)C4=CC=CC=C4 | ||
| Standard InChIKey | WLBUICQBNZXIDJ-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C20H16N4O2S2/c21-23-16(25)12-28-20-22-18-17(15(11-27-18)13-7-3-1-4-8-13)19(26)24(20)14-9-5-2-6-10-14/h1-11H,12,21H2,(H,23,25) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Transglutaminase 2 (TG2) inhibitor (IC50 = 0.25 μM). Binds at GTPase site; reversible. |
LDN-27219 Dilution Calculator
LDN-27219 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.448 mL | 12.2399 mL | 24.4798 mL | 48.9596 mL | 61.1995 mL |
| 5 mM | 0.4896 mL | 2.448 mL | 4.896 mL | 9.7919 mL | 12.2399 mL |
| 10 mM | 0.2448 mL | 1.224 mL | 2.448 mL | 4.896 mL | 6.12 mL |
| 50 mM | 0.049 mL | 0.2448 mL | 0.4896 mL | 0.9792 mL | 1.224 mL |
| 100 mM | 0.0245 mL | 0.1224 mL | 0.2448 mL | 0.4896 mL | 0.612 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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LDN-27219 is a reversible and slow-binding inhibitor of tissue transglutaminase (TGases) with IC50 value of 250nM for TGase 2 [1, 2].
LDN-27219 is discovered as a moderately potent inhibitor of TGase. It shows inhibitory activity against hTGase with IC50 value of 0.6μM. LDN-27219 is also a selective inhibitor. It has no effect on Factor XIIIa or caspase 3 at concentration up to 50μM. Besides that, LDN-27219 is found to be mutually exclusive inhibitors with GTP which is an allosteric inhibitor of TGase. It binds at sites other than the GTP site or the active site of the enzyme. The mechanism of LDN-27219 is also not similar with GTP. It has a modest effect on the binding of calcium. Moreover, it is found that LDN-27219 is a competitive inhibitor of the hTGase-catalyzed hydrolysis of Z-Pro-Gln-Ala-Trp [1].
References:
[1] Case A, Stein R L. Kinetic analysis of the interaction of tissue transglutaminase with a nonpeptidic slow-binding inhibitor. Biochemistry, 2007, 46(4): 1106-1115.
[2] Duval E, Case A, Stein R L, et al. Structure–activity relationship study of novel tissue transglutaminase inhibitors. Bioorganic & medicinal chemistry letters, 2005, 15(7): 1885-1889.
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Kinetic analysis of the interaction of tissue transglutaminase with a nonpeptidic slow-binding inhibitor.[Pubmed:17240993]
Biochemistry. 2007 Jan 30;46(4):1106-15.
Tissue transglutaminase (TGase) is a Ca2+-dependent enzyme that catalyzes cross-linking of intracellular proteins through a mechanism that involves isopeptide bond formation between Gln and Lys residues and is allosterically regulated by GTP. TGase is thought to play a pathogenic role in neurodegenerative diseases by promoting aggregation of disease-specific proteins that accumulate as part of these disorders. Given the role that TGase plays in neurodegenerative disorders, we initiated a research program to discover inhibitors of this enzyme that might ultimately be developed into therapeutic agents. To identify such inhibitors, we screened 110,000 druglike compounds for their ability to inhibit TGase [Case, A., et al. (2005) Anal. Biochem. 338, 237-244]. In this paper, we report the kinetics of interaction of human TGase with one of the inhibitors that we identified, LDN-27219. We found that this compound is a reversible, slow-binding inhibitor that appears not to bind at the enzyme's active site but rather at the enzyme's GTP site, or a site that regulates binding of GTP. Interestingly, the potency and kinetics of inhibition are dependent on substrate structure and suggest a novel mechanism of inhibition that involves differential binding of LDN-27219 to multiple conformational states of this enzyme.
Discovery and structure-activity relationship of potent and selective covalent inhibitors of transglutaminase 2 for Huntington's disease.[Pubmed:22224594]
J Med Chem. 2012 Feb 9;55(3):1021-46.
Tissue transglutaminase 2 (TG2) is a multifunctional protein primarily known for its calcium-dependent enzymatic protein cross-linking activity via isopeptide bond formation between glutamine and lysine residues. TG2 overexpression and activity have been found to be associated with Huntington's disease (HD); specifically, TG2 is up-regulated in the brains of HD patients and in animal models of the disease. Interestingly, genetic deletion of TG2 in two different HD mouse models, R6/1 and R6/2, results in improved phenotypes including a reduction in neuronal death and prolonged survival. Starting with phenylacrylamide screening hit 7d, we describe the SAR of this series leading to potent and selective TG2 inhibitors. The suitability of the compounds as in vitro tools to elucidate the biology of TG2 was demonstrated through mode of inhibition studies, characterization of druglike properties, and inhibition profiles in a cell lysate assay.
Structure-activity relationship study of novel tissue transglutaminase inhibitors.[Pubmed:15780627]
Bioorg Med Chem Lett. 2005 Apr 1;15(7):1885-9.
Thieno[2,3-d]pyrimidin-4-one acylhydrazide derivatives were discovered as moderately potent inhibitors of TGase 2 (tissue transglutaminase) utilizing a fluorescence-based assay that measured TGase 2 catalyzed incorporation of the dansylated Lys derivative alpha-N-Boc-Lys-CH(2)-CH(2)-dansyl into the protein substrate N,N-dimethylated-casein. A SAR study revealed that the acylhydrazide thioether side-chain and the thiophene ring were critical to inhibitory activity.
