SEL120 (SEL120-34A) hydrochloride

Catalog No.S8840 Batch:S884001

Technical Data

Formula	C₁₅H₁₈Br₂N₄.xHCl
Molecular Weight		CAS No.	1609452-30-3
Solubility (25°C)*	In vitro	Water	90 mg/mL
		DMSO	11 mg/mL
		Ethanol	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.)

Biological Activity

Description

SEL120 (SEL120-34, SEL120-34A) is a novel inhibitor of Cyclin-dependent kinase 8 (CDK8) with IC50 values of 4.4 nM and 10.4 nM for CDK8/Cyclin C and CDK19/CyclinC respectively.

Targets

CDK8 ^[1] (Cell-free assay)	CDK19 ^[1] (Cell-free assay)
4.4 nM	10.4 nM

In vitro

SEL120-34A inhibits kinase activities of CDK8/CycC and CDK19/CycC complexes with an IC50 of 4.4 nM and 10.4 nM, respectively. It does not significantly inhibit other members of the CDK family in a single point inhibition assay, namely CDK1, 2, 4, 6, 5, 7 in vitro, with the exception of CDK9, however a calculated IC50 1070 nM, indicated an over 200 fold selectivity against this kinase. SEL120-34A inhibits phosphorylation of STAT1 S727 and STAT5 S726 in cancer cells, inhibits mitogen- induced expression of immediate early response (IER) genes and IFN- responsive genes expression in vitro^[1]. In a broad panel of cancer cell lines, the compound shows the strongest activity in hematological malignancies, especially in selected acute myeloid leukemia (AML) (GI50 12 nM), acute lymphoblastic leukemia (ALL) and mantle cell lymphoma (MCL) models. SEL120−34A could alter transcriptional programs linked to differentiation of leukemia cells^[2].

In vivo

SEL120-34A has favorable pharmacodynamics to be sufficient to affect expression of CDK8 and CDK19- dependent genes in vivo. SEL120-34A treatment causes specific alterations in interferon- responsive genes and inhibits the proliferation of AML cell lines in vivo. SEL120-34A does not affect normal hematopoiesis^[1]. SEL120−34A effectively inhibits tumor growth in subcutaneous responder AML and MCL models when administered orally^[2].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines HCT-116 cells Concentrations 0.1, 0.25, 0.5, 1, 2.5, 5 μM Incubation Time 5 h Method HCT-116 are seeded onto 6-well plates at 2.5×10⁵/well. On the following day, cells are synchronized for 24 h by 0.5% FBS starvation, pretreated with 0.1% DMSO or SEL120-34A at the indicated concentration for 1 h and then supplemented with either 10% FBS, IFNg or IFNa in the presence of the inhibitor (4h). Cells are centrifuged at 1300 rpm for 5 min at 4°C, washed once with 1 ml of ice-cold PBS and stored at -80°C.
Animal Study:^{^[1]}	Animal Models SCID/beige C.B17 female mice xenografted with Colo-205 tumors Dosages 5, 15, 30 and 60 mg/kg BID Administration oral

Cell Assay:^{^[1]}

Cell lines
HCT-116 cells
Concentrations
0.1, 0.25, 0.5, 1, 2.5, 5 μM
Incubation Time
5 h
Method
HCT-116 are seeded onto 6-well plates at 2.5×10⁵/well. On the following day, cells are synchronized for 24 h by 0.5% FBS starvation, pretreated with 0.1% DMSO or SEL120-34A at the indicated concentration for 1 h and then supplemented with either 10% FBS, IFNg or IFNa in the presence of the inhibitor (4h). Cells are centrifuged at 1300 rpm for 5 min at 4°C, washed once with 1 ml of ice-cold PBS and stored at -80°C.

Animal Study:^{^[1]}

Animal Models
SCID/beige C.B17 female mice xenografted with Colo-205 tumors
Dosages
5, 15, 30 and 60 mg/kg BID
Administration
oral

References

Selleck's SEL120 (SEL120-34A) hydrochloride has been cited by 3 publications

LncRNA EILA promotes CDK4/6 inhibitor resistance in breast cancer by stabilizing cyclin E1 protein [ Sci Adv, 2023, 9(40):eadi3821]	PubMed: 37801505
Enhanced T cell effector activity by targeting the Mediator kinase module [ Science, 2022, 378(6620):eabn5647]	PubMed: 36356142
The Oligomeric Assemblies of Cytomegalovirus Core Nuclear Egress Proteins Are Associated with Host Kinases and Show Sensitivity to Antiviral Kinase Inhibitors [ Viruses, 2022, 14(5)1021]	PubMed: 35632762

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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.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.