1. Cell Cycle/DNA Damage
    Apoptosis
  2. CDK
    Apoptosis
  3. LY2857785

LY2857785 

Cat. No.: HY-12293 Purity: 98.88%
Handling Instructions

LY2857785 is a type I reversible and competitive ATP kinase inhibitor against CDK9 (IC50 11 nM) and other transcription kinases CDK8 (IC50 16 nM), and CDK7 (IC50 246 nM).

For research use only. We do not sell to patients.

LY2857785 Chemical Structure

LY2857785 Chemical Structure

CAS No. : 1619903-54-6

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 261 In-stock
Estimated Time of Arrival: December 31
2 mg USD 132 In-stock
Estimated Time of Arrival: December 31
5 mg USD 264 In-stock
Estimated Time of Arrival: December 31
10 mg USD 432 In-stock
Estimated Time of Arrival: December 31
50 mg USD 1680 In-stock
Estimated Time of Arrival: December 31
100 mg USD 2520 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

Based on 4 publication(s) in Google Scholar

Top Publications Citing Use of Products
  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

LY2857785 is a type I reversible and competitive ATP kinase inhibitor against CDK9 (IC50 11 nM) and other transcription kinases CDK8 (IC50 16 nM), and CDK7 (IC50 246 nM).

IC50 & Target[1]

CDK9

0.011 μM (IC50)

CDK8

0.016 μM (IC50)

CDK7

0.246 μM (IC50)

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 μM, and a total of 14 kinases less than 1 μM. At the cellular level, LY2857785 inhibits CTD P-Ser2 and CTD P-Ser5 in U2OS cells at IC50s 0.089 (n=13) and 0.042 (n=1) μM, respectively. However, LY2857785 only induces a moderate G2-M DNA content increase, from 35% to 55%, with EC50 0.135 μM. LY2857785 shows potent compound exposure- and time-dependent cell proliferation inhibition in MV-4-11, RPMI8226, and L363 cells. When incubated between 4 to 24 hours, the cell growth inhibition potency reaches a maximal effect at 8 hours with IC50s 0.04, 0.2, and 0.5 μM for MV-4-11, RPMI8226, and L363 cells, respectively. LY2857785-induced cancer cell apoptosis is also time dependent, reaching maximal potency at 8 hours with IC50 0.5 μM in L363 cells[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

In HCT116 xenograft tumor-bearing mice, LY2857785 demonstrates dose-dependent RNAP II CTD P-Ser2 inhibition potently with TED50 of 4.4 mg/kg and TEC50 of 0.36 μM. LY2857785 also shows significant duration of CTD P-Ser2 inhibition for 3 to 6 hours at TED70 (8 mg/kg) in HCT116 and MV-4-11 nude mice xenograft models. In the nude rat MV-4-11 xenograft model, LY2857785 similarly shows dose-dependent CTD P-Ser2 inhibition for 8 hours at TED70 (7 mg/kg) and TED90 (10 mg/kg). LY2857785 demonstrates the most dramatic tumor regression in the AML MV-4-11 xenograft tumor model either by i.v. bolus in mice or i.v. infusion in rats[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

448.60

Formula

C₂₆H₃₆N₆O

CAS No.

1619903-54-6

SMILES

CC(C1=C2C=C(C3=NC(N[[email protected]]4CC[[email protected]](NC5CCOCC5)CC4)=NC=C3)C=CC2=NN1C)C

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 10 mg/mL (22.29 mM; Need ultrasonic)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.2292 mL 11.1458 mL 22.2916 mL
5 mM 0.4458 mL 2.2292 mL 4.4583 mL
10 mM 0.2229 mL 1.1146 mL 2.2292 mL
*Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 1.

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 1 mg/mL (2.23 mM); Clear solution

  • 2.

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 1 mg/mL (2.23 mM); Clear solution

  • 3.

    Add each solvent one by one:  10% DMSO    90% corn oil

    Solubility: ≥ 1 mg/mL (2.23 mM); Clear solution

*All of the co-solvents are provided by MCE.
References
Kinase Assay
[1]

CDK7 and CDK9 reaction mixtures contain 10 mM Tris-HCl (pH 7.4), 10 mM HEPES, 5 mM DTT, 10 μM ATP, 0.5 μCi 33p-ATP, 10 mM MnCl2, 150 mM NaCl, 0.01% Triton X-100, 2% DMSO, 0.05 mM CDK7/9ptide, and 2 nM CDK7/Mat1/cyclin H, or 2 nM CDK9/cyclin T1, respectively. CDK8/cyclin C reaction is performed in HEPES 30 mM, DTT 2 mM, MgCl2 5 mM, 0.015% Triton X-100, 5 μM ATP, and 400 nM of RBER-CHKStide containing 20 nM of enzyme. LY2857785 in DMSO is diluted serially 1:3 for dose response. Reactions are carried out in 96-well polystyrene plates. The reactions are incubated at room temperature for 60 minutes and followed by termination with 10% H3PO4 or 10% trichloroacetic acid (TCA). For the filter binding assay, reactions are transferred to 96-well filter plates and measured by Microbeta scintillation counter. For ADP Transcreener Fluorescent Polarization Assays, reactions are quenched with ADP detection mix, incubated 2 hours at room temperature and then FP is measured at λex=610 nm, λem=670 nm on a Tecan Ultra 384 plate reader. The concentration of ADP product is calculated from millipolarization (μP) using a prepared ADP/ATP dilution series as a standard curve. Kinase profiling are carried out in 96-well polystyrene plates. Briefly, in a final volume of 25 μL the enzyme is incubated with the appropriate buffer, peptide substrate, and the diluted LY2857785. Reactions are initiated by the addition of ATP/[33P] and the ATP mix is incubated at room temperature for 40 minutes. Reactions are quenched with the addition 5 μL of 3% phosphoric acid, 10 μL of the reaction are spotted onto a filtermat, washed 3 times for 5 minutes in 75 mM phosphoric acid and once in methanol. Once the filters are dry, they are submitted to scintillation counting[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

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 (e.g, LY2857785). 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 with In Situ Cell Death Detection Kit. Both assays are analyzed on Acumen Explorer laser-scanning fluorescence microplate cytometer. Hematologic tumor cells are assayed for cell viability with CellTiter-Glo Luminescent Cell Viability Assay[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Mice and Rats[1]
For xenograft models, human cancer cells U87MG, MV-4-11, A375, and HCT116 are implanted into female nude rats or athymic nude female mice. The animals are dosed with saline, Rapamycin, or LY2857785, respectively. MV-4-11 xenografts in nude mice are treated by LY2857785 (4, 8, and 18 mg/kg) i.v. bolus. MV-4-11 xenografts in nude rats are treated with LY2857785 (3, 6, and 9 mg/kg) 4-hour i.v. infusion. An untreated vehicle control group is administered saline i.v. every 3 days. Flow cytometry analysis is conducted using Beckman Coulter's CXP software. Statistical significance of the effect of LY2857785 and/or control compounds is assessed by Dunnett method, one-way ANOVA.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References

Purity: 98.88%

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Keywords:

LY2857785LY 2857785LY-2857785CDKApoptosisCyclin dependent kinaseInhibitorinhibitorinhibit

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