FIT-039 (FIT039) is an oral, selective and ATP-competitive CDK9 (cyclin-dependent kinase 9) inhibitor with antiviral activity. FIT-039 prevents HSV-1, HSV-2, human adenovirus, and human CMV from replicating (IC50 of 0.69 μM). For inhibiting drug-resistant HSVs and other DNA viruses, FIT-039 is a promising antiviral agent.
Physicochemical Properties
| Molecular Formula | C17H18FN3S |
| Molecular Weight | 315.4104 |
| Exact Mass | 315.12 |
| Elemental Analysis | C, 64.74; H, 5.75; F, 6.02; N, 13.32; S, 10.16 |
| CAS # | 1113044-49-7 |
| Related CAS # | 1113044-49-7 |
| PubChem CID | 25186688 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 460.4±55.0 °C at 760 mmHg |
| Flash Point | 232.2±31.5 °C |
| Vapour Pressure | 0.0±1.1 mmHg at 25°C |
| Index of Refraction | 1.662 |
| LogP | 3.05 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 22 |
| Complexity | 367 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C1=NC=CC(C(NC2=CC(F)=CC=C2N2CCCCC2)=S)=C1 |
| InChi Key | VRKZHYSJZOUICG-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C17H18FN3S/c18-14-4-5-16(21-10-2-1-3-11-21)15(12-14)20-17(22)13-6-8-19-9-7-13/h4-9,12H,1-3,10-11H2,(H,20,22) |
| Chemical Name | N-(5-fluoro-2-piperidin-1-ylphenyl)pyridine-4-carbothioamide |
| Synonyms | FIT-039; KP1115; FIT039; KP-1115; FIT 039; KP 1115 |
| 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 | CDK9/cyclinT1 (IC50 = 5.8 μM); HSV-1 (IC50 = 0.69 μM); HSV-2; CMV |
| ln Vitro |
FIT-039 (30 μM; 3 hours; HEK293 cells) treatment lowers the amount of phosphorylated CTD in infected or noninfected cells compared to what flavopiridol shows. HSV-1 immediate-early genes (IEGs) as well as early and late genes have lower expression levels when FIT-039 is used[1]. FIT-039 has a dose-dependent effect on the HSV-1 genome's ability to replicate (EC50 and EC80 are 0.69 μM and 4.0 μM, respectively)[1]. FIT-039 potently inhibits eight kinases on the 332-kinase panel, except for CDK9: GSK3β, PKN1, haspin, p70s6K, DYRK1B, GSK3α, IRR, and DYRK3. Numerous viruses replicate because of these kinases[1]. |
| ln Vivo |
In a dose-dependent manner, treatment with the FIT-039 ointment twice daily prevents skin lesions and saves male BALB/c mice that have been injected with HSV-1 from dying. 5% to 10% FIT-039 ointment is used to observe lesion healing, and on day 10, 5% ACV ointment is used to observe the full regression of zosteriform spread[1]. FIT-039 has no effect on mice given an excess of this compound (1000 mg/kg/d) for 14 days in terms of body weight gain, and there are no changes seen in the biological markers in the mice's blood[1]. |
| References |
[1]. CDK9 Inhibitor FIT-039 Prevents Replication of Multiple DNA Viruses. J Clin Invest. 2014 Aug;124(8):3479-88. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~100 mg/mL (~317.1 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (7.93 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. 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 (7.93 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (7.93 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 | 3.1705 mL | 15.8524 mL | 31.7048 mL | |
| 5 mM | 0.6341 mL | 3.1705 mL | 6.3410 mL | |
| 10 mM | 0.3170 mL | 1.5852 mL | 3.1705 mL |