TC13172 (TC-13172) is a mixed Lineage Kinase Domain-Like protein (MLKL) inhibitor with single nanomolar potency. As evidence that MLKL should be considered a druggable target, TC13172 may offer useful tools for studying the biological function of MLKL.
Physicochemical Properties
| Molecular Formula | C17H16N4O5S |
| Molecular Weight | 388.397742271423 |
| Exact Mass | 390.1 |
| Elemental Analysis | C, 52.30; H, 4.65; N, 14.35; O, 20.49; S, 8.21 |
| CAS # | 2093393-05-4 |
| Related CAS # | 2093393-05-4 |
| PubChem CID | 134691750 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 0.7 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 27 |
| Complexity | 795 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | ZTQLCNOQWGSELY-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C17H16N4O5S/c1-19-13-14(18-16(19)27(3,25)26)21(17(24)20(2)15(13)23)9-5-7-11-6-4-8-12(22)10-11/h4,6,8,10,22H,9H2,1-3H3 |
| Chemical Name | 3-[3-(3-hydroxyphenyl)prop-2-ynyl]-1,7-dimethyl-8-methylsulfonylpurine-2,6-dione |
| Synonyms | 2093393-05-4 |
| 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
| Targets | MLKL (EC50 = 2±0.6 nM) |
| ln Vitro | The HT-29 cell line is used to assess the anti-necroptosis potency of TC13172; the EC50 value is 20.6 nM. The inhibition potency of TC13172 against cell necroptosis is 2 nM. By firmly attaching to Cys-86, TC13172 prevents MLKL from functioning. The fact that TC13172 decreases MLKL levels in the membrane phase without affecting MLKL's phosphorylation shows that these MLKL inhibitors prevent MLKL from moving to the cell membrane and preventing necroptosis[1]. |
| References |
[1]. Discovery of a new class of highly potent necroptosis inhibitors targeting the mixed lineage kinase domain-like protein.ChemCommun (Camb). 2017 Mar 28;53(26):3637-3640. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~25 mg/mL (~64.4 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (5.79 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 22.5 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: ≥ 2.25 mg/mL (5.79 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 22.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5747 mL | 12.8733 mL | 25.7467 mL | |
| 5 mM | 0.5149 mL | 2.5747 mL | 5.1493 mL | |
| 10 mM | 0.2575 mL | 1.2873 mL | 2.5747 mL |