product name LDC4297 (LDC044297)
Description: LDC4297 is a novel and potent CDK7 inhibitor with IC50 of 0.13±0.06 nM for CDK7 and IC50s between 10 nM and 10,000 nM for all other analyzed CDKs. The affinity of LDC4297 for CDK7 proves to be extremely high. The replication of HCMV in cultured primary human fibroblasts (HFFs) is inhibited by LDC4297 in a concentration-dependent manner with a 50% effective concentration (EC50) value of 24.5 ± 1.3 nM. Notably, CDK7 inhibition by LDC4297 is not associated with general cytotoxicity at submicromolar concentrations.
References: Antimicrob Agents Chemother. 2015 Apr;59(4):2062-71.
432.52
Formula
C23H28N8O
CAS No.
1453834-21-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 86 mg/mL (198.8 mM)
Water: <1 mg/mL
Ethanol: 86 mg/mL (198.8 mM)
Solubility (In vivo)
Synonyms
LDC044297
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19406341
| In Vitro |
In vitro activity: LDC4297 inhibits CDK7 in vitro in the nano-picomolar range. The affinity of LDC4297 for CDK7 proves to be extremely high. The replication of HCMV in cultured primary human fibroblasts (HFFs) is inhibited by LDC4297 in a concentration-dependent manner with a 50% effective concentration (EC50) value of 24.5 ± 1.3 nM. Notably, CDK7 inhibition by LDC4297 is not associated with general cytotoxicity at submicromolar concentrations. In contrast, LDC4297 induces cytotoxicity in a set of tumor cell lines, i.e., already at extremely low, nanomolar concentrations in specific cases. Anti-HCMV activity of LDC4297 is exerted through a multifaceted mode of action that involves an interference with virus-induced Rb phosphorylation. Kinase Assay: Cell Assay: A trypan blue exclusion assay is performed with cultured cells seeded in 24-well plates and incubated with increasing concentrations of antiviral compounds (range, 0.1 to 50 μM) for the durations indicated. Cell staining is achieved with 0.1% trypan blue for 10 min at room temperature before the percentage of viable cells is determined by microscopic counting. |
|---|---|
| In Vivo | The PK analyses of LDC4297 performed thus far have also been highly promising. An analysis of the PK parameters in CD1 mice reveals positive characteristics after oral administration, as demonstrated for a single-dose treatment (100 mg/kg of LDC4297. The half-life (t1/2z) is determined to be 1.6 h, and a time (Tmax) to a mean peak plasma concentration of 1,297.6 ng/ml is reached 0.5 h after administration, with a continued presence of LDC4297 plasma levels for at least 8 h and a bioavailability of 97.7%. |
| Animal model | CD-1 mice |
| Formulation & Dosage | 100 mg/kg; p.o. |
| References | Antimicrob Agents Chemother. 2015 Apr;59(4):2062-71. |
