T-448 is a novel,orally-bioactive, specific and irreversible (covalent) inhibitor of lysine-specific demethylase 1 (LSD1) which is an H3K4 demethylase, with an IC50 of 22 nM. T-448 enhances H3K4 methylation in primary cultured rat neurons. It can improve learning function without causing thrombocytopenia in mice.
Physicochemical Properties
| Molecular Formula | C17H20N4OS |
| Molecular Weight | 328.431901931763 |
| Exact Mass | 328.135 |
| CAS # | 1597426-52-2 |
| Related CAS # | T-448;1597426-53-3 |
| PubChem CID | 118304076 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 2.7 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 23 |
| Complexity | 444 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | CC1=NN=C(S1)NC(=O)C2=CC=CC(=C2)[C@@H]3C[C@H]3NC4CCC4 |
| InChi Key | HQRYNOVKRKLADI-LSDHHAIUSA-N |
| InChi Code | InChI=1S/C17H20N4OS/c1-10-20-21-17(23-10)19-16(22)12-5-2-4-11(8-12)14-9-15(14)18-13-6-3-7-13/h2,4-5,8,13-15,18H,3,6-7,9H2,1H3,(H,19,21,22)/t14-,15+/m0/s1 |
| Chemical Name | 3-[(1S,2R)-2-(cyclobutylamino)cyclopropyl]-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzamide |
| 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 |
| 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 | T-448 improves learning deficits, raises H3K4 methylation levels, and boosts the mRNA expression of genes linked to neuroplasticity, such as brain-derived neurotrophic factor (Bdnf) [1]. |
| ln Vivo | T-448 produces compact formyl-FAD adducts, which have negligible impact on the LSD1-GFI1B complex and great hematological safety in mice. In mice with NMDA receptor hypofunction, T-448 promotes brain H3K4 methylation and partially restores learning function [1]. Even at levels of 100 mg/kg, T-448 enhances H3K4 methylation in the brain without producing hematological adverse effects [1]. |
| Cell Assay |
Cell Viability Assay Cell Types: Primary cultured rat neurons. Tested Concentrations: 0-10μM. Incubation period: 1 day of treatment. Experimental Results: Ucp2 H3K4me2 and Ucp2 mRNA were Dramatically increased. |
| Animal Protocol |
Animal/Disease Models: NR1-hypo mouse[1]. Doses: 1. 10 mg/kg. Doses: po (po (oral gavage)) 3 weeks. Experimental Results: H3K4me2 levels around the Bdnf, Arc, and Fos genes increased in a dose-dependent manner in the mouse hippocampus. The results were a partial but statistically significant and dose-dependent rescue of correct choice rates in NR1-hypo mice. |
| References |
[1]. T-448, a specific inhibitor of LSD1 enzyme activity, improves learning function without causing thrombocytopenia in mice. Neuropsychopharmacology. 2018 Dec 22. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0448 mL | 15.2239 mL | 30.4479 mL | |
| 5 mM | 0.6090 mL | 3.0448 mL | 6.0896 mL | |
| 10 mM | 0.3045 mL | 1.5224 mL | 3.0448 mL |