Y-320 is a novel, potent and orally bioactive, phenylpyrazoleanilide immunomodulator that blocks CD4 T cells stimulated with IL-15 from producing IL-17 with an IC50 range of 20 to 60 NM. Oral administration of Y-320 (0.3-3 mg/kg) decreased IL-17 mRNA expression and significantly slowed the progression of arthritis and joint degeneration in mice with type II collagen-induced arthritis (CIA). Anti-murine tumor necrosis factor (TNF-α) monoclonal antibody and Y-320 worked in synergy. Y-320 (0.3–1 mg/kg) alleviated CIA in cynomolgus monkeys. These findings suggested that Y-320 might make a good candidate for rheumatoid arthritis (RA) treatment.
Physicochemical Properties
| Molecular Formula | C27H29CLN6O2 | |
| Molecular Weight | 505.01 | |
| Exact Mass | 504.204 | |
| Elemental Analysis | C, 64.21; H, 5.79; Cl, 7.02; N, 16.64; O, 6.34 | |
| CAS # | 288250-47-5 | |
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| PubChem CID | 22227931 | |
| Appearance | Off-white to pink solid powder | |
| Density | 1.3±0.1 g/cm3 | |
| Boiling Point | 631.2±55.0 °C at 760 mmHg | |
| Flash Point | 335.6±31.5 °C | |
| Vapour Pressure | 0.0±1.8 mmHg at 25°C | |
| Index of Refraction | 1.675 | |
| LogP | 3.58 | |
| Hydrogen Bond Donor Count | 1 | |
| Hydrogen Bond Acceptor Count | 6 | |
| Rotatable Bond Count | 5 | |
| Heavy Atom Count | 36 | |
| Complexity | 784 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | ClC1C([H])=C([H])C(=C([H])C=1[H])N1C(C([H])([H])[H])=C(C([H])=N1)C(N([H])C1C([H])=C([H])C(=C(C#N)C=1[H])N1C([H])([H])C([H])([H])C([H])(C([H])([H])C1([H])[H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H])=O |
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| InChi Key | BWZNJVZTAWBIFG-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C27H29ClN6O2/c1-19-25(18-30-34(19)24-5-2-21(28)3-6-24)27(35)31-22-4-7-26(20(16-22)17-29)33-10-8-23(9-11-33)32-12-14-36-15-13-32/h2-7,16,18,23H,8-15H2,1H3,(H,31,35) | |
| Chemical Name | 1-(4-chlorophenyl)-N-[3-cyano-4-(4-morpholin-4-ylpiperidin-1-yl)phenyl]-5-methylpyrazole-4-carboxamide | |
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| 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 |
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| 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 | IL-15; IL-17 | ||
| ln Vitro | Y-320 also prevents mouse CD4 T cells stimulated with IL-15, CXCL12, and anti-CD3 mAb from producing IFN-γ and TNF-α. [1] | ||
| ln Vivo | Y-320 (0.3–3 mg/kg p.o.) shows therapeutic effects on collagen-induced arthritis (CIA) in cynomolgus monkeys as well as mice with a reduction in IL-17 mRNA in arthritic joints. Additionally, when combined with an anti-TNF mAb, Y-320 has a synergistic effect on mice with chronically worsening CIA. [1] | ||
| Cell Assay | Y-320 inhibited IL-17 production by CD4 T cells induced by IL-15 with IC50 values of 20-60 NM. | ||
| Animal Protocol |
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| References |
[1]. A new phenylpyrazoleanilide, y-320, inhibits interleukin 17 production and ameliorates collagen-induced arthritis in mice and cynomolgus monkeys. Pharmaceuticals (Basel). 2013 Dec 23;7(1):1-17. [2]. Small molecule Y-320 stimulates ribosome biogenesis, protein synthesis, and aminoglycoside-induced premature termination codon readthrough. PLoS Biol. 2021 May 3;19(5):e3001221. [3]. Y-320, a novel immune-modulator, sensitizes multidrug-resistant tumors to chemotherapy. Am J Transl Res. 2020 Feb 15;12(2):551-562. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.5 mg/mL (0.99 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 5.0 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: ≥ 0.5 mg/mL (0.99 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 5.0 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: ≥ 0.5 mg/mL (0.99 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 5.0 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 | 1.9802 mL | 9.9008 mL | 19.8016 mL | |
| 5 mM | 0.3960 mL | 1.9802 mL | 3.9603 mL | |
| 10 mM | 0.1980 mL | 0.9901 mL | 1.9802 mL |