Name: Lexibulin (CYT997)
Brand: Selleck Chemicals
SKU: S2195
Availability: InStock
Rating: 5 (8 reviews)

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Quality Control

Batch: Purity: 99.91%

99.91

Related Targets	Akt Wnt/beta-catenin HSP PKC ROCK Integrin Bcr-Abl Actin FAK Kinesin
Other Microtubule Associated Inhibitors	Nocodazole MMAF Patupilone (Epothilone B) CW069 Combretastatin A4 ABT-751 (E7010) Epothilone A Cucurbitacin B TAI-1 Vindoline

Solubility

In vitro
Batch:

DMSO : 86 mg/mL (197.91 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 20 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	4.3mg/ml (9.90mM)	Taking the 1 mL working solution as an example, add 50 μL of 86 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.61mg/ml (1.40mM)	Taking the 1 mL working solution as an example, add 50 μL of 12.2 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

+

%

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	434.53	Formula	C₂₄H₃₀N₆O₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	917111-44-5	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	SRI-32007			Smiles	CCCC(C1=CN=CC=C1)NC2=NC(=NC=C2C)C3=CC(=C(C=C3)NC(=O)NCC)OC

Mechanism of Action

Targets/IC₅₀/Ki	Microtubules (cancer cell lines) 10 nM-100 nM
In vitro	Lexibulin (CYT997) (1 μM) treatment for 24 hours in A549 cells induces rapid reorganization of microtubules including the destruction of the existing microtubule network and accumulation of tubulin in plaques within the cytoplasm of some cells, leading to significant cell morphology alterations including the loss of adhesion and cell rounding. It displays potent cytotoxic activity against a range of 16 cancer cells with IC50 ranging from 9 nM for HepG2 to 101 nM for KHOS/NP. Especially, this compound exhibits potent activity against HCT15 cells, known to possess the multidrug resistance mechanism Pgp (MDR⁺), with IC50 of 52 nM. Through inhibition of microtubule polymerization, it blocks the cell cycle at the G2-M boundary, and induces an increase in phosphorylated Bcl-2 and increased expression of cyclin B1, as well as caspase-3 activation and the generation of poly (ADP-ribose) polymerase. Its treatment causes a rapid and reversible increase in the permeability of HUVEC monolayers with IC50 of ~80 nM at 1 hour of exposure. Consistent with the disruption of cellular tubulin, it potently inhibits proliferation, induces cell cycle arrest and most importantly apoptosis of both human myeloma cell lines (HMCLs) and primary MM cells.
Kinase Assay	Turbidimetric assay for tubulin polymerization
Kinase Assay	The effect of Lexibulin (CYT997) on microtubule polymerization is determined using a conventional turbidimetric assay with bovine neuronal tubulin, in which microtubule assembly is monitored by an increase in absorbance at 340 nm. Increasing concentrations of this compound are added to 100 μL of tubulin/GTP/glycerol. Turbidimetric assays of microtubule assembly are performed by incubating bovine microtubule protein in cuvettes at 37 °C in a thermostatically controlled spectrophotometer, measuring the change in absorbance at 340 nm over time in PEM buffer [80 nM PIPES (pH 6.9), 2 mM MgCl₂, 0.5 mM EGTA, and 5% glycerol].
In vivo	The half-life of Lexibulin (CYT997) for oral administration (2.5 hours) to rats is slightly longer than that for intravenous administration (1.5 hours), with the absolute oral bioavailability being 50% to 70%. Oral administration of this compound induces dose-dependent inhibition of tumor growth of PC3 xenografts in mice, more potently compared with paclitaxel. It is also effective in an orthotopic syngeneic model using the mouse breast cancer 4T1 cells, which are some refractory to Paclitaxel treatment. A single dose of CYT997 (7.5 mg/kg, i.p.) reduces tumor blood flow significantly at 6 hours in liver metastases, to a similar extent as the positive control CA4P dosed at 100 mg/kg. Treatment with this compound (15 mg/kg/day) significantly prolongs the survival in a murine model of aggressive systemic myelomatosis.
References	[1] https://pubmed.ncbi.nlm.nih.gov/19887548/ [2] https://pubmed.ncbi.nlm.nih.gov/19907921/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT00650949	Terminated	Glioblastoma Multiforme	Gilead Sciences	November 2009	Phase 1\|Phase 2
NCT00664378	Terminated	Relapsed and Refractory Multiple Myeloma	Gilead Sciences	January 2008	Phase 2

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Lexibulin (CYT997) Microtubule Associated inhibitor

Chemical Structure

Molecular Weight: 434.53