BAY-598 R-isomer (R-BAY598) is the R-enantiomer of BAY589 which is a peptide-competitive SMYD2 inhibitor with antineoplastic activity.
Physicochemical Properties
| Molecular Formula | C22H20CL2F2N6O3 |
| Molecular Weight | 525.335409164429 |
| Exact Mass | 524.094 |
| Elemental Analysis | C, 50.30; H, 3.84; Cl, 13.50; F, 7.23; N, 16.00; O, 9.14 |
| CAS # | 1906920-28-2 |
| Related CAS # | 1906920-28-2 (BAY598 R-isomer);1906919-67-2 (BAY598);1906920-07-7 (BAY598 recamic mixture); |
| PubChem CID | 125407509 |
| Appearance | Beige solid powder. |
| Density | 1.5±0.1 g/cm3 |
| Boiling Point | 651.3±65.0 °C at 760 mmHg |
| Flash Point | 347.7±34.3 °C |
| Vapour Pressure | 0.0±2.1 mmHg at 25°C |
| Index of Refraction | 1.629 |
| LogP | 2.43 |
| 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 | ClC1=C(C=CC(=C1)C1[C@@H](CN(/C(=N/C2C=CC=C(C=2)OC(F)F)/NC#N)N=1)N(C(CO)=O)CC)Cl |
| 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 | (R,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 R-isomer; BAY-598 R-isomer; BAY 598 R-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 |
The highly selective SMYD2 small molecule inhibitor BAY-598 treatment blocked in vitro methylation of MAPKAPK3 by SMYD2 but had no activity against the SMYD2-related KMT SMYD3, which methylated its substrate, MAP3K2, irrespective of the presence of BAY-598 . BAY-598 treatment reduced the growth of Kras;p53 mutant PDAC cells after 9 d in culture but had little impact on the growth of Kras;p53;Smyd2 mutant cells, further supporting the specificity of this small molecule inhibitor of SMYD2 as well as a role for SMYD2 in promoting the growth of PDAC cells. Notably, the chemotherapeutic gemcitabine was far more potent in inhibiting clonal expansion of Kras;p53 mutant PDAC cells when administered in combination with BAY-598 or used to treat cells lacking SMYD2 , suggesting that chemotherapy treatment and SMYD2 inhibition cooperate to target PDAC cells in this assay . Human PDAC cell lines such as SW1990 and MIA PaCa2 cells are largely resistant to acute treatment (48 h or less) with chemotherapeutic agents like gemcitabine and doxorubicin and are only marginally inhibited by acute treatment with the SMYD2 inhibitor BAY-598. However, these PDAC cells were highly sensitive to acute treatment with a combination therapy consisting of low-dose treatment with doxorubicin and BAY-598 . [1] |
| References | Genes Dev.2016 Apr 1;30(7):772-85. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (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 |