LDC4297

Catalog No.S7992 Batch:S799201

Technical Data

Formula	C₂₃H₂₈N₈O
Molecular Weight	432.52	CAS No.	1453834-21-3
Solubility (25°C)*	In vitro	DMSO	86 mg/mL (198.83 mM)
		Ethanol	86 mg/mL (198.83 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

LDC4297 is a novel CDK7 inhibitor (IC50=0.13±0.06 nM for CDK7 versus IC50s between 10 nM and 10,000 nM for all other analyzed CDKs).

Targets

CDK7 ^[1]
(Cell-free assay)

0.13 nM

In vitro

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^[1].

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 (t_1/2z) 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%^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines human fibroblasts Concentrations 0.1 to 50 μM Incubation Time 3 days Method 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.
Animal Study:^{^[1]}	Animal Models CD-1 mice Dosages 100 mg/kg Administration oral administration

Cell Assay:^{^[1]}

Cell lines
human fibroblasts
Concentrations
0.1 to 50 μM
Incubation Time
3 days
Method
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.

Animal Study:^{^[1]}

Animal Models
CD-1 mice
Dosages
100 mg/kg
Administration
oral administration

References

[1] Hutterer C, et al. Antimicrob Agents Chemother. 2015, 59(4):2062-71.

Selleck's LDC4297 has been cited by 4 publications

CDK7/12/13 inhibition targets an oscillating leukemia stem cell network and synergizes with venetoclax in acute myeloid leukemia [ EMBO Mol Med, 2022, e14990]	PubMed: 35253392
Elevation of effective p53 expression sensitizes wild-type p53 breast cancer cells to CDK7 inhibitor THZ1 [ Cell Commun Signal, 2022, 20(1):96]	PubMed: 36058938
Ubiquitylation of MYC couples transcription elongation with double-strand break repair at active promoters [ Mol Cell, 2021, S1097-2765(20)30956-4]	PubMed: 33453168
MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation. [ Mol Cell, 2019, 74(4):674-687]	PubMed: 30928206

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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