BAY-598 (BAY598 S-isomer) is novel, potent, selective and peptide-competitive small molecule inhibitor of lysine methyltransferase SMYD2 with potential antitumor activity. SMYD2 is overexpressed in various cancers. BAY-598 is a chemical probe that has a unique chemotype relative to the current SMYD2 chemical probe LLY-507. BAY-598 inhibits in vitro methylation of p53K370 with IC50 = 27 nM and has more than 100-fold selectivity over other histone methyltransferases and other non-epigenetic targets. BAY-598 inhibits the methylation of p53K370 in cells with IC50 < 1 µM.
Physicochemical Properties
| Molecular Formula | C22H20CL2F2N6O3 |
| Molecular Weight | 525.335409164429 |
| Exact Mass | 524.09 |
| Elemental Analysis | C, 50.30; H, 3.84; Cl, 13.50; F, 7.23; N, 16.00; O, 9.14 |
| CAS # | 1906919-67-2 |
| Related CAS # | 1906919-67-2 (S-isomer);1906920-28-2 (BAY598 R-isomer);1906920-07-7 (BAY598 recamic mixture); |
| PubChem CID | 117072551 |
| Appearance | Beige Solid powder |
| LogP | 4.4 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 35 |
| Complexity | 854 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | CCN([C@H]1CN(N=C1C2=CC(=C(C=C2)Cl)Cl)C(=NC3=CC(=CC=C3)OC(F)F)NC#N)C(=O)CO |
| InChi Key | OTTJIRVZJJGFTK-SFHVURJKSA-N |
| InChi Code | InChI=1S/C22H20Cl2F2N6O3/c1-2-31(19(34)11-33)18-10-32(30-20(18)13-6-7-16(23)17(24)8-13)22(28-12-27)29-14-4-3-5-15(9-14)35-21(25)26/h3-9,18,21,33H,2,10-11H2,1H3,(H,28,29)/t18-/m0/s1 |
| Chemical Name | (S,E)-N-(1-(N'-cyano-N-(3-(difluoromethoxy)phenyl)carbamimidoyl)-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl)-N-ethyl-2-hydroxyacetamide |
| Synonyms | BAY598; BAY 598; BAY-598 S-isomer |
| 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 | Treatment with BAY-598 prevents SMYD2 from methylating MAPKAPK3 in vitro, but it has no effect on the KMT SMYD2-associated SMYD2. After nine days in culture, BAY-598 administration inhibited the growth of Kras;p53 mutant PDAC cells, but had no effect on the growth of Kras;p53;Smyd2 mutant cells [1]. |
| References |
[1]. Coordination of stress signals by the lysine methyltransferase SMYD2 promotes pancreaticcancer. Genes Dev. 2016 Apr 1;30(7):772-85. [2]. Discovery and Characterization of a Highly Potent and Selective Aminopyrazoline-Based in Vivo Probe (BAY-598) for the Protein Lysine Methyltransferase SMYD2. J Med Chem. 2016 May 26;59(10):4578-600. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~125 mg/mL (~237.94 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.96 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 (3.96 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 | 1.9035 mL | 9.5176 mL | 19.0353 mL | |
| 5 mM | 0.3807 mL | 1.9035 mL | 3.8071 mL | |
| 10 mM | 0.1904 mL | 0.9518 mL | 1.9035 mL |