| Bioactivity | FIT-039 is a selective, ATP-competitive and orally active CDK9 inhibitor with an IC50 of 5.8 μM for CKD9/cyclin T1. FIT-039 does not inhibit other CDKs and other kinases. FIT-039 inhibits replication of HSV-1 (IC50 of 0.69 μM), HSV-2, human adenovirus, and human CMV. FIT-039 is a promising antiviral agent for inhibiting drug-resistant HSVs and other DNA viruses. | |||||||||
| Invitro | FIT-039 (30 μM; 3 hours; HEK293 cells) treatment decreases phosphorylated CTD in the infected or noninfected cells to a level lower than that shown by Flavopiridol. FIT-039 reduces the expression levels of HSV-1 immediate-early genes (IEGs) and early and late genes[1].FIT-039 inhibits replication of the HSV-1 genome in a dose-dependent manner (EC50 and EC80 are 0.69 μM and 4.0 μM, respectively)[1].FIT-039 potently suppresses 8 kinases (GSK3β, PKN1, haspin, p70s6K, DYRK1B, GSK3α, IRR, and DYRK3) other than CDK9 on the 332-kinase panel. These kinases are involved in the replication of various viruses[1]. Western Blot Analysis[1] Cell Line: | |||||||||
| In Vivo | Treatment with the FIT-039 ointment twice a day suppresses skin lesions and rescues mice (male BALB/c mice injected with HSV-1) from lethality in a dose-dependent manner. The healing of lesions is observed with 5% to 10% FIT-039 ointment, leading to the complete regression of zosteriform spread on day 10, which is also observed with the 5% ACV ointment[1].FIT-039 does not affect body weight gain in mice administrated with an overdose of this compound (1000 mg/kg/d) for 14 days, and no changes are observed in biological markers in their blood[1]. | |||||||||
| Name | FIT-039 | |||||||||
| CAS | 1113044-49-7 | |||||||||
| Formula | C17H18FN3S | |||||||||
| Molar Mass | 315.41 | |||||||||
| Appearance | Solid | |||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | |||||||||
| Storage |
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| Reference | [1]. Makoto Yamamoto, et al. CDK9 Inhibitor FIT-039 Prevents Replication of Multiple DNA Viruses. J Clin Invest. 2014 Aug;124(8):3479-88. |