SPD-304 is a novel, potent and selective inhibitor of tumor necrosis factor α (TNFα) with an IC50 of 22 µM for preventing binding to the TNF Receptor 1 (TNFR1). Angiotensin (Ang) II/Ang II receptor type 1 (AT1) and tumor necrosis factor (TNF)-α play critical roles in neuropathic pain and nociception, respectively.
Physicochemical Properties
| Molecular Formula | C32H32F3N3O2 |
| Molecular Weight | 547.6106 |
| Exact Mass | 547.244 |
| Elemental Analysis | C, 70.19; H, 5.89; F, 10.41; N, 7.67; O, 5.84 |
| CAS # | 869998-49-2 |
| Related CAS # | SPD304 dihydrochloride;1049741-03-8 |
| PubChem CID | 5327044 |
| Appearance | White to off-white solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 589.2±50.0 °C at 760 mmHg |
| Flash Point | 310.2±30.1 °C |
| Vapour Pressure | 0.0±1.7 mmHg at 25°C |
| Index of Refraction | 1.583 |
| LogP | 8.23 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 40 |
| Complexity | 910 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C1C(CN(CCN(CC2C3C(=CC=CC=3)N(C3C=C(C(F)(F)F)C=CC=3)C=2)C)C)=COC2C1=CC(C)=C(C)C=2 |
| InChi Key | JZNXLPPJRFFECJ-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C32H32F3N3O2/c1-21-14-28-30(15-22(21)2)40-20-24(31(28)39)18-37(4)13-12-36(3)17-23-19-38(29-11-6-5-10-27(23)29)26-9-7-8-25(16-26)32(33,34)35/h5-11,14-16,19-20H,12-13,17-18H2,1-4H3 |
| Chemical Name | 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one |
| Synonyms | SPD-304; SPD 304; SPD304 |
| 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 | TNFα (IC50 = 22 µM) |
| ln Vitro | SPD304 (2 μM) significantly rescues the survivability of aHSCs, reduces the production of lipid hydroxides, and increased intracellular GSH. The co-treatment of GA (75 μM) and SPD304 (2 μM) downregulates TRADD almost 2-fold (w/o inhibitor vs. w/ inhibitor) and pRIP3 1.4-fold compared to GA alone, and promotes caspase 8 activation[4]. |
| ln Vivo | SPD304 cannot be used in vivo due to its high toxicity[3]. |
| References |
[1]. Small-Molecule Inhibition of TNF-α. Science 11 Nov 2005. [2]. Rationally designed less toxic SPD-304 analogs and preliminary evaluation of their TNF inhibitory effects. Arch Pharm (Weinheim). 2014 Nov;347(11):798-805. [3]. Identification of an in vivo orally active dual-binding protein-protein interaction inhibitor targeting TNFα through combined in silico/in vitro/in vivo screening. Sci Rep. 2017 Jun 13;7(1):3424. [4]. PLoS One. 2015 Mar 27;10(3):e0120713. |
Solubility Data
| Solubility (In Vitro) |
Water: ~100 mg/mL (~182.6 mM) DMSO: ~50 mg/mL (~91.3 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.28 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 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: 1.25 mg/mL (2.28 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 12.5 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. Solubility in Formulation 3: ≥ 1.25 mg/mL (2.28 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 12.5 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 | 1.8261 mL | 9.1306 mL | 18.2612 mL | |
| 5 mM | 0.3652 mL | 1.8261 mL | 3.6522 mL | |
| 10 mM | 0.1826 mL | 0.9131 mL | 1.8261 mL |