UAMC-3203 (UAMC3203) is a novel and selective Ferroptosis inhibitor with an IC50 value of 12 nM. It has anti-inflammatory and antioxidant properties. The radical-sequestering antioxidant Ferrostatin-1 (Fer-1) can prevent the iron-catalyzed, nonapoptotic form of controlled necrosis known as ferroptosis from damaging cell membranes. Novel inhibitors derived from the Fer-1 scaffold effectively inhibited ferroptosis but had solubility problems. After daily injections of UAMC-3203 for 4 weeks, no toxicity was seen in mice. In silico, UAMC-3203 inserts quickly into a phospholipid bilayer, which is consistent with the way these drugs currently work. In conclusion, these analogs are novel lead compounds with therapeutic potential in relevant ferroptosis-driven disease models. They exhibit in vivo efficacy, have better properties than Fer-1, and have superior properties to Fer-1.
Physicochemical Properties
| Molecular Formula | C25H37N5O2S |
| Molecular Weight | 471.6586 |
| Exact Mass | 471.27 |
| Elemental Analysis | C, 63.66; H, 7.91; N, 14.85; O, 6.78; S, 6.80 |
| CAS # | 2271358-64-4 |
| Related CAS # | UAMC-3203 hydrochloride;2271358-65-5 |
| PubChem CID | 137701965 |
| Appearance | White to off-white a solution in ethanol |
| LogP | 3.5 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 10 |
| Heavy Atom Count | 33 |
| Complexity | 652 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | HSYSVXKJIVUNBR-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C25H37N5O2S/c31-33(32,28-15-18-30-16-13-26-14-17-30)23-11-12-24(29-22-9-5-2-6-10-22)25(19-23)27-20-21-7-3-1-4-8-21/h1,3-4,7-8,11-12,19,22,26-29H,2,5-6,9-10,13-18,20H2 |
| Chemical Name | 3-(benzylamino)-4-(cyclohexylamino)-N-(2-piperazin-1-ylethyl)benzenesulfonamide |
| Synonyms | UAMC-3203 free base; UAMC-3203; UAMC3203; UAMC 3203 |
| 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 | Ferroptosis (IC50 = 12 nM) |
| ln Vitro | UAMC-3203 has a remarkable t1/2 when incubated with human and rat microsomes (t1/2 = 20.5 h and t1/2 = 16.5 h, respectively), but it is discovered to be relatively less stable when incubated with murine microsomes (t1/2 = 3.46 h)[1]. |
| ln Vivo | UAMC-3203 significantly lowers the plasma levels of lactate dehydrogenase (LDH) in mice. As is typical for lipophilic basic compounds, it leaves the bloodstream quickly and is distributed again throughout the body's tissues. All of the tissues that were examined (liver, kidney, and lungs) contained significant levels of UAMC-3203[1]. |
| References |
[1]. Discovery of Novel, Drug-Like Ferroptosis Inhibitors with in Vivo Efficacy. J Med Chem. 2018 Nov 21;61(22):10126-10140. |
Solubility Data
| Solubility (In Vitro) |
DMSO: 94~250 mg/mL (199.3~530 mM) Ethanol: ~94 mg/mL (~199.3 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.41 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 (4.41 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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: ≥ 2.08 mg/mL (4.41 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 | 2.1202 mL | 10.6009 mL | 21.2017 mL | |
| 5 mM | 0.4240 mL | 2.1202 mL | 4.2403 mL | |
| 10 mM | 0.2120 mL | 1.0601 mL | 2.1202 mL |