LY2857785

Catalog No.S7511 Batch:S751101

Technical Data

Formula	C₂₆H₃₆N₆O
Molecular Weight	448.60	CAS No.	1619903-54-6
Solubility (25°C)*	In vitro	Ethanol	42 mg/mL (93.62 mM)
		DMSO	23 mg/mL (51.27 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.)

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Biological Activity

Description

LY2857785 is a type I reversible and competitive ATP kinase inhibitor against CDK9(IC50=0.011 μM) and also inhibits other transcription kinases CDK8(IC50=0.016 μM) and CDK7 (IC50=0.246 μM).

Targets

CDK9 ^[1] (Cell-free assay)	CDK8 ^[1] (Cell-free assay)	CDK7 ^[1] (Cell-free assay)
0.011 μM	0.016 μM	0.246 μM

In vitro

LY2857785 shows good selectivity against a panel of 114 protein kinases, with only 5 other protein kinases inhibited with potency (IC50) less than 0.1 μmol/L, and a total of 14 kinases less than 1 μmol/L. At the cellular level, LY2857785 inhibits CTD P-Ser2 and CTD P-Ser5 in U2OS cells at IC50s 0.089 and 0.042 μM. Although LY2857785 inhibits CDK4, CDK6, and CDK2 enzymatic activities, it does not induce G1-S cell-cycle arrest. It also has activity against CDK1 (Histone H1 P-T153 inhibition IC50 0.241 μmol/L). However LY2857785 only induces a moderate G2–M DNA content increase, from 35% to 55%, with EC50 0.135 μmol/L. LY2857785 inhibits hematologic and solid tumor cell proliferation and induces apoptosis in vitro^[1].

In vivo

LY2857785 inhibits RNAP II CTD Ser2 phosphorylation in vivo. It demonstrates potent antitumor growth efficacy in preclinical tumor models and increases animal survival. No significant weight loss is observed in the nude mouse study while animal mortality is observed in these studies at LY2957785 high-dose groups^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines Solid tumor cells/hematologic cell lines; i.e. Human A549 (lung carcinoma), U2OS (osteosarcoma), HCT116 (colorectal carcinoma), U87MG (glioblastoma), A375 (malignant melanoma), MV-4-11 (biphenotypic B-myelomonocytic leukemia), RPMI 8226 (myeloma), L363 (multiple myeloma) cancer cell lines Concentrations 0, 0.1, 0.2, 0.4, 0.6, 0.8, 1 μM Incubation Time 2-72 h Method Solid tumor cells are plated in poly-d-lysine coated and hematologic cell lines are seeded in noncoated 96-well plates overnight before being treated with compounds. Solid tumor cells are fixed with Prefer for 20 minutes at room temperature and permeated with 0.1% Triton X-100 in PBS for 15 minutes. Caspase-3 expression is measured by immunofluorescence with antiactivated caspase-3. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) activity is measured. Hematologic tumor cells are assayed for cell viability.
Animal Study:^{^[1]}	Animal Models female nude rats or athymic nude female mice Dosages 4, 8, 12 mg/kg Administration i.v.

Cell Assay:^{^[1]}

Cell lines
Solid tumor cells/hematologic cell lines; i.e. Human A549 (lung carcinoma), U2OS (osteosarcoma), HCT116 (colorectal carcinoma), U87MG (glioblastoma), A375 (malignant melanoma), MV-4-11 (biphenotypic B-myelomonocytic leukemia), RPMI 8226 (myeloma), L363 (multiple myeloma) cancer cell lines
Concentrations
0, 0.1, 0.2, 0.4, 0.6, 0.8, 1 μM
Incubation Time
2-72 h
Method
Solid tumor cells are plated in poly-d-lysine coated and hematologic cell lines are seeded in noncoated 96-well plates overnight before being treated with compounds. Solid tumor cells are fixed with Prefer for 20 minutes at room temperature and permeated with 0.1% Triton X-100 in PBS for 15 minutes. Caspase-3 expression is measured by immunofluorescence with antiactivated caspase-3. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) activity is measured. Hematologic tumor cells are assayed for cell viability.

Animal Study:^{^[1]}

Animal Models
female nude rats or athymic nude female mice
Dosages
4, 8, 12 mg/kg
Administration
i.v.

References

[1] Yin T, et al. Mol Cancer Ther. 2014, 13(6):1442-56.

Selleck's LY2857785 has been cited by 2 publications

ChemR23 activation reprograms macrophages toward a less inflammatory phenotype and dampens carcinoma progression [ Front Immunol, 2023, 14:1196731]	PubMed: 37539056
Inhibitors Targeting CDK9 Show High Efficacy against Osimertinib and AMG510 Resistant Lung Adenocarcinoma Cells [ Cancers (Basel), 2021, 13(15)3906]	PubMed: 34359807

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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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