TMC647055 (TMC-647055) is a potent HCV NS5B polymerase inhibitor with the potential to be used for the treatment of HCV infection. TMC647055 has nanomolar cellular potency (EC(50) of 82 nM) with minimal associated cell toxicity (CC(50)>20 μM) and promising pharmacokinetic profiles in rats and dogs. TMC647055 showed promising in vitro bioactive compound, kinetic, and virological profile that is currently undergoing clinical evaluation. TMC647055 is currently being evaluated in clinical trials.
Physicochemical Properties
| Molecular Formula | C32H38N4O6S |
| Molecular Weight | 606.732326984406 |
| Exact Mass | 606.251 |
| CAS # | 1204416-97-6 |
| Related CAS # | TMC647055 Choline salt |
| PubChem CID | 44556044 |
| Appearance | Typically exists as solid at room temperature |
| Density | 1.4±0.1 g/cm3 |
| Index of Refraction | 1.669 |
| LogP | 3.77 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 43 |
| Complexity | 1170 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S1(N(C)CCOCCN(C)C(C2=CC3C=C(C=CC=3C3=C(C4C=CC(C(N1)=O)=CC=4N3C2)C1CCCCC1)OC)=O)(=O)=O |
| InChi Key | UOBYJVFBFSLCTQ-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C32H38N4O6S/c1-34-13-15-42-16-14-35(2)43(39,40)33-31(37)22-9-11-27-28(19-22)36-20-24(32(34)38)17-23-18-25(41-3)10-12-26(23)30(36)29(27)21-7-5-4-6-8-21/h9-12,17-19,21H,4-8,13-16,20H2,1-3H3,(H,33,37) |
| Chemical Name | 28-cyclohexyl-22-methoxy-10,16-dimethyl-9,9-dioxo-13-oxa-9λ6-thia-1,8,10,16-tetrazapentacyclo[16.8.1.12,6.13,26.020,25]nonacosa-2,4,6(29),18,20(25),21,23,26(28)-octaene-7,17-dione |
| 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 Huh7-Luc cells, TMC647055 exhibits antiviral activity with an EC90 value of 0.3 μM [1]. With an EC50 value of 82 nM, TMC647055 exhibits strong combinatorial action in cellular HCV detection [2]. |
| ln Vivo | TMC647055 (Compound 18a) (2 mg/kg IV; 10 mg/kg PO) demonstrated acceptable PK profiles characterized by high oral bioavailability following a single oral dose of 10 mg/kg combined with moderate doses and high systemic exposure. Plasma clearance and volume of distribution are low [2]. |
| Animal Protocol |
Animal/Disease Models: Rat[2] Doses: 2 mg/kg; 10mg/kg Route of Administration: 2mg/kg, intravenous (iv) (iv)injection; 10mg/kg, oral administration; Single Experimental Results:No. Cl (L/h/kg) Cmax(ng /mL) [Liver] (ng/mL) L/PF (%) TMC647055 (Compound 18a) 3.2 440 7800 46 ＞66 |
| References |
[1]. TMC647055, a potent nonnucleoside hepatitis C virus NS5B polymerase inhibitor with cross-genotypic coverage. Antimicrob Agents Chemother. 2012 Sep;56(9):4676-4684. [2]. Finger loop inhibitors of the HCV NS5b polymerase. Part II. Optimization of tetracyclic indole-based macrocycle leading to the discovery of TMC647055. Bioorg Med Chem Lett. 2012 Jul 1;22(13):4437-43. |
| Additional Infomation | TMC647055 has been used in trials studying the treatment of Hepatitis C, Chronic Hepatitis C, Hepatitis C, Chronic, and Chronic Hepatitis C Virus. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6482 mL | 8.2409 mL | 16.4818 mL | |
| 5 mM | 0.3296 mL | 1.6482 mL | 3.2964 mL | |
| 10 mM | 0.1648 mL | 0.8241 mL | 1.6482 mL |