Rabusertib

SKU: orb1301087

Description

Rabusertib (IC-83) is a selective checkpoint kinase 1 (Chk1) inhibitor investigated for its chemosensitizing potential in oncology research. It has been evaluated in preclinical and clinical studies for solid tumors, including pancreatic and non-small cell lung cancers, to enhance the efficacy of DNA-damaging chemotherapeutic agents.

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 911222-45-2
• MW: 436.3
• Purity: 98.00%
• Formula: C₁₈H₂₂BrN₅O₃
• SMILES: Cc1cnc(NC(=O)Nc2cc(Br)c(C)cc2OC[C@@H]2CNCCO2)cn1
• Target: Chk,PDK,Autophagy
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (2.29 mM);DMSO:40 mg/mL (91.68 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  CaMK II:1550 nM|PDK1:893 nM|Chk1:7 nM|NTRK1:12000 nM|VEGFR3:2128 nM|RSK2:5700 nM|JNK1:4930 nM|MET:2200 nM|Chk2:12000 nM
• In Vivo:
  In xenograft models, LY2603618 delays tumor growth when given in combination with pemetrexed.
• In Vitro:
  Chk1 is an ATP-dependent serine-threonine kinase and a key component in the DNA replication-monitoring checkpoint system activated by double-stranded breaks (DSBs). Chk1 contributes to all currently defined cell cycle checkpoints, including G1/S, intra-S-phase, G2/M, and the mitotic spindle checkpoint. By inhibiting the activity of chk1, Rabusertib prevents the repair of DNA caused by DNA-damaging agents, thus potentiating the antitumor efficacies of various chemotherapeutic agents. However, preClinicalal data involving Rabusertib has not been published until now. Inhibition of Chk1 is predicted to enhance the effects of antimetabolites, such as gemcitabine. Rabusertib treatment impairs DNA synthesis, increases DNA damage (via mitotic defects), induces apoptosis, and has synergistic activity with pemetrexed, especially in p53 mutant tumor cells.
• Cell Research:
  LY2603618 is prepared in DMSO (10 mM) and stock, and then diluted 1000-fold into medium. Cells are plated at 2.5×103 per well, on 96-well tissue culture plates and incubated for one cell doubling (18-24 h). Gemcitabine dilutions are set up by half-log steps across a final concentration range of 1-1000 nM. LY2603618 is prepared by dilutions in DMSO to 5000× final concentration, and then diluted 1000-fold into medium to generate 5× stocks for addition to wells. Approximately 24 h after Gemcitabine addition, LY2603618 is added. Each combination is done in triplicate. After a period of two cell doublings following LY2603618 addition, MTS/PMS reagent is added to each well according to the manufacturer's instructions. Absorbance is read on a Spectra Max 250 spectrophotometer at 490 nm and the data analyzed with GraphPad Prism 4.0. Dose-response curves are fit by non-linear regression, with bottom fits constrained to 0 % inhibition.

Storage & Handling

• Storage: store at low temperature | 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

Autophagy, Chk1, Checkpoint Kinase (Chk), Inhibitor, IC83, IC-83, IC 83, PDK1, inhibit, LY 2603618, LY2603618, LY-2603618, Rabusertib

Compound Identifiers

PubChem CID

11955855