Lexibulin

SKU: orb1306503

Description

Lexibulin (CYT-997) is a potent small-molecule tubulin polymerization inhibitor (IC50: 10-100 nM) that induces G2/M cell cycle arrest by disrupting mitotic spindle formation. This mechanism has demonstrated antitumor activity in both cellular assays and in vivo models, supporting its research application in oncology and vascular disruption.

Research Area

Cell Biology, Immunology & Inflammation, Metabolism Research, Signal Transduction

Key Properties

• CAS Number: 917111-44-5
• MW: 434.53
• Purity: 98.87%
• Formula: C₂₄H₃₀N₆O₂
• SMILES: CCC[C@H](Nc1nc(ncc1C)-c1ccc(NC(=O)NCC)c(OC)c1)c1cccnc1
• Target: Apoptosis,ROS,Microtubule Associated,Reactive Oxygen Species
• Solubility: Ethanol:16 mg/mL (36.82 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (7.59 mM);DMSO:80 mg/mL (184.11 mM)

Bioactivity

• Target IC50:
  Microtubule (cancer cells):10 nM-100 nM
• In Vivo:
  CYT997 exhibits toxicity across 16 cancer cell lines (IC50: 9/101 nM in HepG2 and KHOS/NP cells) and shows notably higher efficacy in HCT15 cells, which possess the multi-drug resistance mechanism Pgp (MDR+) (IC50: 52 nM). When treating A549 cells for 24 hours, CYT997 (1 μM) induces rapid reorganization of microtubules, including disruption of the existing microtubule network and accumulation of cytoplasmic microtubule proteins at the foci, significantly altering cell morphology. This entails a loss of adhesion in cells and a reduction in cell number. By inhibiting microtubule polymerization, CYT997 arrests the cell cycle at the G2-M phase boundary, leads to an increase in phosphorylated Bcl-2, and elevates the expression of cyclin B1, activation of caspase-3, and production of PARP. Treatment with CYT997 for one hour considerably enhances the permeability of HUVEC monolayers (IC50: 80 nM) in a rapid and reversible manner. Consistent with the disruption of cellular microtubule proteins, CYT997 effectively halts proliferation, induces cell cycle arrest, and triggers apoptosis in human bone marrow cell lines and primary MM cells.
• In Vitro:
  CYT997 (7.5 mg/kg, i.p.) administration to liver metastasis significantly reduced blood flow at 6 hours, with an effect similar to the positive control CA4P (100 mg/kg). Consistent with its in vitro anti-myeloma activity, treatment with CYT997 (15 mg/kg/day) in an aggressive systemic myeloid leukemia mouse model extended lifespan. Compared to its intravenous half-life (1.5 hours), the half-life of CYT997 when administered orally to rats was slightly longer (2.5 hours), with an absolute oral bioavailability of 50%-70%. In PC3 xenograft mice, oral administration of CYT997 showed a stronger inhibitory effect on tumor growth than Paclitaxel, and this effect was dose-dependent. CYT997 was also effective in a syngeneic model carrying mouse breast cancer 4T1 cells, which exhibits certain resistance to Paclitaxel treatment.
• Cell Research:
  Cells are exposed to various concentrations of CYT997 for ~72 hours. Cell proliferation is assessed with either the Alamar blue or MTT assays. For MTT assays, 5 mg/mL of MTT is added to all wells, plates are incubated for 6 hours at 37 °C, and then lysis buffer is added (10% SDS in 0.01 N HCl) and absorbance is measured at 620 nm in a BMG Technologies Lumistar or Polarstar plate reader. For Alamar blue assays, Alamar blue (10 μL/well) is added to each well and the plates are incubated at 37 °C for 4 hours. The fluorescence is then measured using a fluorescence plate reader with an excitation filter at 544 nm and an emission filter at 590 nm. For cell cycle analysis, cells are fixed and permeabilized with 70% ethanol in PBS and incubated at 4 °C overnight. RNase-treated samples (10 μg RNase/mL for 20 minutes at 37 °C) are stained with propidium iodide (5 μg/mL) at 4 °C for a minimum of 10 minutes. Cell cycle variables are determined by fluorescence-activated cell sorting (FACS) analysis using a Beckman-Coulter Quanta SC MPL system and analyzed using CXP Software. For apoptosis analysis, cells are detached and collected. Annexin staining is done using the Vybrant Apoptosis Assay Kit. Cells are stored on ice and analyzed on a Beckman Coulter Quanta MPL within 1 hour of preparation. Annexin V–positive cells are determined using two-channel analysis.(Only for Reference)

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

inhibit, MicrotubuleAssociated, Microtubule Associated, Microtubule/Tubulin, microtubule, Inhibitor, Lexibulin, CYT 997, CYT997, CYT-997, Apoptosis, ReactiveOxygenSpecies, Reactive Oxygen Species

Compound Identifiers

PubChem CID

11351021