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WAY-204688 (WAY204688; WAY 204688; SIM688; SIM-688) is a novel, potent, selective and orally bioactive agonist of estrogen receptor (ER-α) and also an inhibitor of NF-κB transcriptional activity with anti-inflammatory effects. It inhibits NF-κB-luciferase (NF-κB-luc) with an IC50 of 122 ± 30 nM in HAECT-1 cells. WAY-204688 has the potential to be used for the treatment of rheumatoid arthritis.
Physicochemical Properties
| Molecular Formula | C34H31F3N2O2 |
| Molecular Weight | 556.617359399796 |
| Exact Mass | 556.233 |
| CAS # | 796854-35-8 |
| PubChem CID | 9829162 |
| Appearance | White to off-white solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 708.7±60.0 °C at 760 mmHg |
| Flash Point | 382.4±32.9 °C |
| Vapour Pressure | 0.0±2.3 mmHg at 25°C |
| Index of Refraction | 1.589 |
| LogP | 7.99 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 41 |
| Complexity | 938 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | [C@@H](C1C=CC=CC=1OC)(C1=CC=CC2C=CC=CC1=2)[C@@](C)(C#N)C(N1CCC(C2C=CC=C(C(F)(F)F)C=2)CC1)=O |
| InChi Key | JZPONCMNBSEYQW-MOJIJOCKSA-N |
| InChi Code | InChI=1S/C34H31F3N2O2/c1-33(22-38,32(40)39-19-17-23(18-20-39)25-11-7-12-26(21-25)34(35,36)37)31(29-14-5-6-16-30(29)41-2)28-15-8-10-24-9-3-4-13-27(24)28/h3-16,21,23,31H,17-20H2,1-2H3/t31-,33?/m0/s1 |
| Chemical Name | (2S,3S)-3-(2-methoxyphenyl)-2-methyl-3-(naphthalen-1-yl)-2-(4-(3-(trifluoromethyl)phenyl)piperidine-1-carbonyl)propanenitrile |
| Synonyms | SIM-688; WAY-204688; SIM 688; WAY204688; SIM688; WAY 204688 |
| 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 | WAY-204688 is ER-dependent; in human aortic endothelial cell lines (HAECT-1), it is only active when hER is coexpressed with NF-κB-luciferase. In vitro tests are performed to investigate WAY-204688's interactions with ERα and ERβ. WAY-204688 extracts [3H]E2 with an IC50 of 2.43 μM from the ERα ligand binding domain protein (LBD) and with an IC50 of 1.5 μM from the ERβ ligand binding domain protein (LBD)[1]. |
| ln Vivo | The effectiveness of WAY-204688 (5 mg/kg per day, po daily for 5 weeks) to inhibit the four proinflammatory genes (MHC, invariant chain (MHI), VCAM-1, RANTES, and TNF-α) is assessed in vivo. WAY-204688's impact on uterine wet weight and gene product induction is contrasted with that of 17α-ethinyl 17β-estradiol (EE at 10 μg/kg daily) using the identical paradigm. WAY-204688 is being further characterized in a number of preclinical models of inflammatory illness. WAY-204688 is effective in the adjuvant-induced arthritis model (AIA) in Lewis rats when administered at a dose of 0.3 mg/kg daily, po[1]. |
| References | [1]. Caggiano TJ, et al. Estrogen receptor dependent inhibitors of NF-kappaB transcriptional activation-1 synthesis and biological evaluation of substituted 2-cyanopropanoic acid derivatives: pathway selective inhibitors of NF-kappaB, a potential treatment fo |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~179.66 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.49 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 | 1.7966 mL | 8.9828 mL | 17.9656 mL | |
| 5 mM | 0.3593 mL | 1.7966 mL | 3.5931 mL | |
| 10 mM | 0.1797 mL | 0.8983 mL | 1.7966 mL |