ML188 is a potent and selective non-covalent SARS-CoV 3CLpro inhibitor with an IC50 of 1.5 μM. The X-ray structure of SARS-CoV 3CLpro bound with ML188 was instrumental in guiding subsequent rounds of chemistry optimization. ML188 provides an excellent starting point for the further design and refinement of 3CLpro inhibitors that act by a noncovalent mechanism of action.
Physicochemical Properties
| Molecular Formula | C26H31N3O3 |
| Molecular Weight | 433.5426 |
| Exact Mass | 433.236 |
| Elemental Analysis | C, 72.03 H, 7.21 N, 9.69 O, 11.07 |
| CAS # | 1417700-13-0 |
| Related CAS # | 1417699-67-2 (racemic);1417700-12-9 (S-isomer);1417700-13-0 (R-isomer); |
| PubChem CID | 46897844 |
| Appearance | White to off-white solid powder |
| LogP | 5 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 32 |
| Complexity | 644 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | O=C([C@@]([H])(C1=C([H])N=C([H])C([H])=C1[H])N(C(C1=C([H])C([H])=C([H])O1)=O)C1C([H])=C([H])C(=C([H])C=1[H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])N([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] |
| InChi Key | JXGIYKRRPGCLFV-JOCHJYFZSA-N |
| InChi Code | InChI=1S/C26H31N3O3/c1-25(2,3)19-11-13-20(14-12-19)29(24(31)21-10-8-16-32-21)22(18-9-7-15-27-17-18)23(30)28-26(4,5)6/h7-17,22H,1-6H3,(H,28,30)/t22-/m1/s1 |
| Chemical Name | N-[(1R)-2-(tert-Butylamino)-2-oxo-1-pyridin-3-ylethyl]-N-(4-tert-butylphenyl)furan-2-carboxamide |
| Synonyms | ML188; ML-188; ML 188; |
| 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 |
In cell culture, ML188 (0-30 μM; 48 hours) effectively inhibits SARS-CoV replication[1]. The SARS-CoV 3CLpro inhibitor Probe ML188 has a non-covalent mode of action, moderate molecular weight, and proven antiviral activity. The antiviral EC50 value of ML188 in both SARS-CoV-infected and mock-infected cells ranges from 12.9 to 13.4 μM[1]. |
| Cell Assay |
Cell Line: Vero E6 cells (mock-infected or infected with SARS-CoV) Concentration: 3, 4, 5, 8,10, 15, 20, 30 μM Incubation Time: 48 hour Result: Against mock-infected and SARS-CoV infected cells. |
| References |
[1]. Discovery, synthesis, and structure-based optimization of a series of N-(tert-butyl)-2-(N-arylamido)-2-(pyridin-3-yl) acetamides (ML188) as potent noncovalent small molecule inhibitors of the severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL protease. J Med Chem. 2013 Jan 24;56(2):534-46. |
| Additional Infomation | N-[(1R)-2-(tert-butylamino)-2-oxo-1-(3-pyridinyl)ethyl]-N-(4-tert-butylphenyl)-2-furancarboxamide is a member of furans and an aromatic amide. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~250 mg/mL (~576.65 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (14.42 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 62.5 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: ≥ 6.25 mg/mL (14.42 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 62.5 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: ≥ 6.25 mg/mL (14.42 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 62.5 mg/mL clear DMSO stock solution to 900 μL 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 | 2.3066 mL | 11.5330 mL | 23.0659 mL | |
| 5 mM | 0.4613 mL | 2.3066 mL | 4.6132 mL | |
| 10 mM | 0.2307 mL | 1.1533 mL | 2.3066 mL |