Ac-FLTD-CMK is a pepdie-based inhibitor of caspases 1, 5 and 4. It is a gasdermin D (GSDMD)-derived and specific inflammatory caspases inhibitor.
Physicochemical Properties
| Molecular Formula | C26H37CLN4O8 |
| Molecular Weight | 569.0470 |
| Exact Mass | 568.23 |
| Elemental Analysis | C, 54.88; H, 6.55; Cl, 6.23; N, 9.85; O, 22.49 |
| CAS # | 2376255-48-8 |
| Related CAS # | 2376255-48-8; |
| PubChem CID | 155906572 |
| Appearance | White to off-white solid powder |
| LogP | 0.2 |
| Hydrogen Bond Donor Count | 6 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 16 |
| Heavy Atom Count | 39 |
| Complexity | 878 |
| Defined Atom Stereocenter Count | 5 |
| SMILES | C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)CCl)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)C)O |
| InChi Key | UCWNTWGHVCSMJP-WPUDHWPRSA-N |
| InChi Code | InChI=1S/C26H37ClN4O8/c1-14(2)10-19(30-24(37)20(28-16(4)33)11-17-8-6-5-7-9-17)25(38)31-23(15(3)32)26(39)29-18(12-22(35)36)21(34)13-27/h5-9,14-15,18-20,23,32H,10-13H2,1-4H3,(H,28,33)(H,29,39)(H,30,37)(H,31,38)(H,35,36)/t15-,18+,19+,20+,23+/m1/s1 |
| Chemical Name | (3S)-3-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-5-chloro-4-oxopentanoic acid |
| Synonyms | Ac-FLTD-CMK |
| 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: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). 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 | Ac-FLTD-CMK inhibits pyroptosis downstream of canonical and atypical inflammasomes, decreases IL-1 following NLRP3 inflammasome activation, and prevents GSDMD from being cleaved by caspase-1, -4, -5, and -11 in vitro. 1β released by macrophages. On the other hand, Ac-FLTD-CMK did not cause cell death or inhibit caspase-3. When caspase-1 was complexed with Ac-FLTD-CMK, the crystal structure showed that hydrogen bonds and destination contacts were involved in a wide range of enzyme-to-peer responses [1]. |
| References |
[1]. Mechanism of gasdermin D recognition by inflammatory caspases and their inhibition by a gasdermin D-derived peptide inhibitor. Proc Natl Acad Sci U S A. 2018 Jun 26;115(26):6792-6797. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~175.73 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.39 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 (4.39 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 (4.39 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7573 mL | 8.7866 mL | 17.5731 mL | |
| 5 mM | 0.3515 mL | 1.7573 mL | 3.5146 mL | |
| 10 mM | 0.1757 mL | 0.8787 mL | 1.7573 mL |