KMH-233 is a potent and selective LAT1 Inhibitor 1. KMH-233 inhibited the uptake of LAT1 substrate, L-leucin as well as cell growth. It also significantly potentiated the efficacy of bestatin and cisplatin even at low concentrations (25 μM). KMH-233 may be a promising agent or adjuvant especially for the treatment of prostate cancer.
Physicochemical Properties
| Molecular Formula | C32H25N7O5 |
| Molecular Weight | 587.584806203842 |
| Exact Mass | 587.191 |
| CAS # | 1941174-13-5 |
| Related CAS # | (R)-KMH-233 |
| PubChem CID | 154730690 |
| Appearance | White to yellow solid powder |
| LogP | 2 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 44 |
| Complexity | 1160 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | CNC(=O)COC1=CC=C(C=C1)C2=C(C3=NC4=CC=CC=C4N3C(=C2C#N)NC(=O)C5=CC=CC(=C5)C[C@@H](C(=O)O)N)C#N |
| InChi Key | MLNOOVGSMCJSCE-DEOSSOPVSA-N |
| InChi Code | InChI=1S/C32H25N7O5/c1-36-27(40)17-44-21-11-9-19(10-12-21)28-22(15-33)29-37-25-7-2-3-8-26(25)39(29)30(23(28)16-34)38-31(41)20-6-4-5-18(13-20)14-24(35)32(42)43/h2-13,24H,14,17,35H2,1H3,(H,36,40)(H,38,41)(H,42,43)/t24-/m0/s1 |
| Chemical Name | (S)-2-amino-3-(3-((2,4-dicyano-3-(4-(2-(methylamino)-2-oxoethoxy)phenyl)benzo[4,5]imidazo[1,2-a]pyridin-1-yl)carbamoyl)phenyl)propanoic acid |
| Synonyms | KMH-233 KMH 233 KMH233. |
| 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 | By blocking the binding and transport of necessary neutral amino acids, KMH-233 can stop cancer cells from growing [1]. KMH-233 exhibits a noteworthy decrease in cell proliferation, with an IC50 of 124 µM[1]. KMH-233 inhibits cell growth by 53% and 50%, respectively, and is an effective supplement that can boost the anti-proliferative activity of Bestatin (100 µM) and cisplatin (100 µM) at a lower dose of 25 µM[1]. |
| Cell Assay |
Cell Proliferation Assay[1] Cell Types: MCF-7 Cell Tested Concentrations: 0.5-1000 μM Incubation Duration: 72 hrs (hours) Experimental Results: demonstrated significant reduction in cell growth with IC50 of 124 μM. |
| References |
[1]. A Selective and Slowly Reversible Inhibitor of l-Type Amino Acid Transporter 1 (LAT1) Potentiates Antiproliferative Drug Efficacy in Cancer Cells. J Med Chem. 2016;59(12):5740-5751. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~170.19 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.25 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 (4.25 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7019 mL | 8.5095 mL | 17.0190 mL | |
| 5 mM | 0.3404 mL | 1.7019 mL | 3.4038 mL | |
| 10 mM | 0.1702 mL | 0.8509 mL | 1.7019 mL |