Bioymifi is an DR5 activator (Kd = 1.2 µM; IC50 = 2 µM). Independent of TRAIL, Bioymifi triggers apoptosis through the TRAIL-related apoptosis-inducing ligand (DR5) death receptor. Apoptosis can be brought on by Bioymifi acting as a single agent to cause DR5 clustering and aggregation. The death receptors DR4 and DR5 are used by the substance tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) to activate apoptosis.
Physicochemical Properties
| Molecular Formula | C22H12BRN3O4S |
| Molecular Weight | 494.319 |
| Exact Mass | 492.973 |
| Elemental Analysis | C, 53.46; H, 2.45; Br, 16.16; N, 8.50; O, 12.95; S, 6.49 |
| CAS # | 1420071-30-2 |
| Related CAS # | 1420071-30-2 |
| PubChem CID | 70678419 |
| Appearance | Brown to reddish brown solid powder |
| Density | 1.8±0.1 g/cm3 |
| Index of Refraction | 1.791 |
| LogP | 4.8 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 31 |
| Complexity | 841 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C(/C(SC1=N)=C/C2=CC=C(O2)C3=CC(C(N4)=O)=C(C=C3)C4=O)N1C5=CC=C(C=C5)Br |
| InChi Key | ULBOWKXOFOTCMU-NLDKGBHCSA-N |
| InChi Code | InChI=1S/C22H12BrN3O4S/c23-12-2-4-13(5-3-12)26-21(29)18(31-22(26)24)10-14-6-8-17(30-14)11-1-7-15-16(9-11)20(28)25-19(15)27/h1-10,24H,(H,25,27,28)/b18-10-,24-22? |
| Chemical Name | 5-[5-[(Z)-[3-(4-bromophenyl)-2-imino-4-oxo-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl]isoindole-1,3-dione |
| Synonyms | Bioymifi |
| 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
| Targets | DR5 receptor (Kd = 1.2 μM) |
| ln Vitro | In T98G cells, Bioymifi can induce cell death without the assistance of the Smac mimetic. Bioymifi induces the processing of caspase-3 into smaller fragments at a concentration of 10 μM. For bioymifi-induced cell death to occur, caspase-8 and the associated extrinsic apoptotic pathway are necessary. DR5-dependent death pathways are induced by Bioymifi, wholly unaffected by TRAIL. With a Kd of 1.2 μM, Bioymifi binds the DR5 ECD but has low affinity for the DR4 ECD. In buffer solutions, it is not very soluble. By interacting with and facilitating the aggregation of DR5, Bioymifi aids in the promotion of apoptosis. The ability of bioymifi to aggregate DR5 at micromolar concentrations is potent enough to cause apoptosis in a variety of cancer cells[1]. |
| Cell Assay | Plotted as a function of A2C2 or bioymifi concentration are the dose-response curves for bioymifi and A2C2 in T98G cells. A2C2 or bioymifi, alone or in combination with 1 μM Smac mimetic (SM), are applied to human glioblastoma (T98G) cells in a range of concentrations for 48 hours. A2C2 or bioymifi-free treatment is used to normalize the corresponding cell survival. |
| References |
[1]. Small-molecule activation of the TRAIL receptor DR5 in human cancer cells. Nat Chem Biol. 2013 Feb;9(2):84-9. |
| Additional Infomation |
Bioymifi is a small molecule that acts as a tumor necrosis factor-related apoptosis-induced ligand (TRAIL) mimetic. Upon binding to the death receptor 5 (DR5) on cancer cells, bioymifi triggers apoptosis, possibly through a caspase-dependent pathway. Bioymifi is currently being investigated as an anti-tumor agent. Mechanism of Action In cancer cells, tumor necrosis factor (TNF)-related apoptosis-induced ligand (TRAIL) initiates apoptosis by binding to death receptor 5 (DR5). In contrast, normal cells express high levels of decoy receptors (DcRs) that partially or completely lack the functional death domain (DD). Therefore, the binding of TRAIL on normal cells does not induce cell death. Because of this, small molecules that mimic the activity of TRAIL may have the potential to act as chemotherapeutic agents. Bioymifi mimics the activity of TRAIL, and upon binding to the extracellular domain (ECD) of DR5, it induces clustering and aggregation in cancer cells, leading to apoptosis. |
Solubility Data
| Solubility (In Vitro) | DMSO: 12.5~43 mg/mL (25.3~9 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 1.25 mg/mL (2.53 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 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: 8.33 mg/mL (16.85 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O 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 | 2.0230 mL | 10.1149 mL | 20.2298 mL | |
| 5 mM | 0.4046 mL | 2.0230 mL | 4.0460 mL | |
| 10 mM | 0.2023 mL | 1.0115 mL | 2.0230 mL |