NDI-091143 (NDI091143) is a novel and potent inhibitor of human ATP-citrate lyase (ACLY) with anticancer activity. ATP-citrate lyase (ACLY) is a central metabolic enzyme and catalyses the ATP-dependent conversion of citrate and coenzyme A (CoA) to oxaloacetate and acetyl-CoA. The acetyl-CoA product is crucial for the metabolism of fatty acids, the biosynthesis of cholesterol8, and the acetylation and prenylation of proteins.
Physicochemical Properties
| Molecular Formula | C20H14CLF2NO5S |
| Molecular Weight | 453.8437 |
| Exact Mass | 453.024 |
| CAS # | 2375840-87-0 |
| Related CAS # | 2375840-87-0 |
| PubChem CID | 137796782 |
| Appearance | White to off-white solid powder |
| LogP | 4.9 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 30 |
| Complexity | 700 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | ClC1=CC(C(=O)OC)=CC(=C1O)S(NC1=C(C=C(C(C2C=CC=CC=2)=C1)F)F)(=O)=O |
| InChi Key | YSTSHUWHIDBZAK-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C20H14ClF2NO5S/c1-29-20(26)12-7-14(21)19(25)18(8-12)30(27,28)24-17-9-13(15(22)10-16(17)23)11-5-3-2-4-6-11/h2-10,24-25H,1H3 |
| Chemical Name | Methyl 3-chloro-5-(N-(4,6-difluoro-[1,1'-biphenyl]-3-yl)sulfamoyl)-4-hydroxybenzoate |
| Synonyms | NDI091143; NDI 091143; NDI-091143 |
| 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 | Thermal shift experiments reveal that NDI-091143 gives high stability to the full-length ACLY and N-terminal segments. Thermal shift data are consistent with limited proteolysis experiments using full-length ACLY, where NDI-091143 together with Mg-ATP provided the greatest protection against chymotrypsin digestion [1]. |
| References |
[1]. An allosteric mechanism for potent inhibition of human ATP-citrate lyase. Nature. 2019 Apr;568(7753):566-570. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~220.34 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.58 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 20.8 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: ≥ 2.08 mg/mL (4.58 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 20.8 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: ≥ 2.08 mg/mL (4.58 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 20.8 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 | 2.2034 mL | 11.0171 mL | 22.0342 mL | |
| 5 mM | 0.4407 mL | 2.2034 mL | 4.4068 mL | |
| 10 mM | 0.2203 mL | 1.1017 mL | 2.2034 mL |