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Zelnecirnon (RPT-193; RPT193) is a novel and potent inhibitor of CCR4 with anti-inflammatory activity and may be used for allergic inflammation in atopic dermatitis, and asthma. It acts by inhibiting the recruitment of Th2 inflammatory immune cells into inflamed tissues.
Physicochemical Properties
| Molecular Formula | C27H34CL3N5O2 |
| Molecular Weight | 566.95 |
| Exact Mass | 565.177 |
| CAS # | 2366152-15-8 |
| PubChem CID | 139344142 |
| Appearance | White to off-white solid powder |
| LogP | 4.1 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 37 |
| Complexity | 811 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | [C@]1(C)(C(O)=O)C[C@@H](N2CCC[C@H](C3CN(C4=NC(C)=C(Cl)C(N[C@@H](C5=CC=C(Cl)C=C5Cl)C)=N4)C3)C2)C1 |
| InChi Key | ANPSFQZLPNWKHR-BPZFHHOVSA-N |
| InChi Code | InChI=1S/C27H34Cl3N5O2/c1-15(21-7-6-19(28)9-22(21)29)31-24-23(30)16(2)32-26(33-24)35-13-18(14-35)17-5-4-8-34(12-17)20-10-27(3,11-20)25(36)37/h6-7,9,15,17-18,20H,4-5,8,10-14H2,1-3H3,(H,36,37)(H,31,32,33)/t15-,17+,20-,27-/m1/s1 |
| Chemical Name | (1R,3r)-3-((R)-3-(1-(5-chloro-4-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-methylpyrimidin-2-yl)azetidin-3-yl)piperidin-1-yl)-1-methylcyclobutane-1-carboxylic acid |
| Synonyms | RPT-193 RPT193 ZelnecirnonRPT 193 |
| 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 | Zelnecirnon has an IC50 of about 370 nM and inhibits Th2 cell chemotaxis or migration at concentrations of 1 nM–10 μM[2]. |
| ln Vivo | A mouse model of acute ovalbumin (OVA)-induced atopic dermatitis has shown that zelnecirnon (100 mg/kg; oral; once daily; 2 days, 1 day before OVA challenge) reduces skin inflammation [2]. |
| Animal Protocol |
Animal/Disease Models: Mouse acute ovalbumin (OVA)-induced atopic dermatitis model [2] Doses: 100 mg/kg Route of Administration: po (oral gavage); one time/day; lasts for 2 days, starting 1 day before OVA challenge (In mouse ears) Experimental Results: Significant reduction in ear thickness. |
| References |
[1]. RPT193, an oral CCR4 inhibitor: Efficacy results from a randomized, placebo-controlled Phase 1b monotherapy trial in patients with moderate-to-severe atopic dermatitis[C]//EXPERIMENTAL DERMATOLOGY. 111 RIVER ST, HOBOKEN 07030-5774, NJ USA: WILEY, 2021, 30: 40-41. [2]. Development and first-in-human characterization of a potent oral CCR4 antagonist for the treatment of atopic dermatitis[C]//Journal of Investigative Dermatology. STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA: ELSEVIER SCIENCE INC, 2020, 140(7): S77-S77. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~176.38 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 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 25.0 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: ≥ 2.5 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 25.0 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: ≥ 2.5 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 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 | 1.7638 mL | 8.8191 mL | 17.6382 mL | |
| 5 mM | 0.3528 mL | 1.7638 mL | 3.5276 mL | |
| 10 mM | 0.1764 mL | 0.8819 mL | 1.7638 mL |