LY2857785

SKU: orb1296235

Description

LY2857785 is a potent, reversible, and competitive ATP-competitive inhibitor targeting CDK7, CDK8, and CDK9 with IC50 values of 246 nM, 16 nM, and 11 nM, respectively. This small molecule is a valuable research tool for studying transcriptional regulation and cell cycle progression in both in vitro and in vivo cancer research models.

Research Area

Cell Biology

Key Properties

• CAS Number: 1619903-54-6
• MW: 448.6
• Purity: 99.68%
• Formula: C₂₆H₃₆N₆O
• SMILES: CC(C)c1n(C)nc2ccc(cc12)-c1ccnc(N[C@H]2CC[C@@H](CC2)NC2CCOCC2)n1
• Target: Apoptosis,CDK
• Solubility: DMSO:10 mg/mL (22.29 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (2.23 mM)

Bioactivity

• Target IC50:
  CDK9:11 nM|CDK8:16 nM|CDK7:246 nM
• In Vivo:
  In HCT116 xenograft tumor-bearing mice, LY2857785 potently demonstrates dose-dependent RNAP II CTD P-Ser2 inhibition (TED50: 4.4 mg/kg; TEC50: 0.36 μM), with a significant duration of inhibition for 3 to 6 hours at TED70 (8 mg/kg) in both 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).
• In Vitro:
  At the cellular level, LY2857785 inhibits CTD P-Ser2 and CTD P-Ser5 in U2OS cells (IC50s: 0.089 and 0.042 μM). 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 for MV-4-11, RPMI8226, and L363 cells (IC50s: 0.04, 0.2, and 0.5 μM). LY2857785-induced cancer cell apoptosis is also time-dependent, reaching maximal potency at 8 hours with IC50 0.5 μM in L363 cells.
• Cell Research:
  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 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 anti-activated 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.
• Animal Research:
  For xenograft models, human cancer cells A375, U87MG, MV-4-11, 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 the Dunnett method, one-way ANOVA.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Inhibitor, inhibit, LY 2857785, LY2857785, LY-2857785, Apoptosis, CDK7, CDK, CDK8, CDK9, Cyclin dependent kinase

Compound Identifiers

PubChem CID

78357764