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Lexibulin hydrochloride (CYT-997), the hydrochloride salt of CYT997, is a potent VDA-vascular disrupting agent and also a potent microtubule polymerization/mitotic inhibitor with potential anticancer activity. It inhibits the proliferation of various cancer cells with IC50s of 10-100 nM. It belongs to the so called microtubule-destablizer which inhibits the dynamic instability and polymerization of tubulin.
| ln Vitro |
In vitro, lexibulin (CYT-997) inhibits tubulin polymerization with an IC50 of roughly 3 μmol/L by traditional turbidimetry (as opposed to the half-maximum inhibitory concentration of colchicine, which is 2 μmol/L in the same circumstances). Tuberculin polymerization. Furthermore, as demonstrated by fluorescent microscopy, lexibulin has the capacity to reversibly damage the microtubule network within cells. The application of Lexibulin (1 μM) to A549 cells causes a fast reconfiguration of microtubules, causing some cells to accumulate tubulin in intracytoplasmic plaques and others to break the preexisting microtubule network. The morphology of the cells underwent notable alterations after 24 hours, such as rounding and lack of adhesion. Following a one-hour Lexibulin treatment, cells quickly recovered their original microtubule structure. These effects were reversible. All of the information points to lexibulin as an anticancer medication that upsets tubulin-containing structures rather than stabilizes them. The G2-M phase was observed in 15% and 19% of vehicle-treated cells at 15 and 24 hours (respectively), but 38% and 43% of cells treated with 1 μM Lexibulin displayed G2-M phase at the same time point. phase G2-M. Further evidence that cells halted at the G2-M boundary may not exit back to G1, as in the normal cell cycle, but are instead likely to be driven to apoptosis and cell death comes from the fact that only 66% of total cells were in G1, S, and G2-M phases 24 hours after Lexibulin administration [1]. Lexibulin efficiently reduces proliferation, produces cell cycle arrest, and—most importantly—induces apoptosis in human myeloma cell lines (HMCL) and genuine MM cells, all of which are consistent with the breakdown of cellular tubulin [2].
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| ln Vivo |
Oral administration of Lexibulin (CYT-997) was started 13 days following cell engraftment in a xenograft model using the human prostate cancer cell line PC3, at which point tumors were evidently obvious. The tumor development is significantly inhibited by lexibulin (CYT-997) at doses up to and including parenterally administered paclitaxel at the highest dose. In liver metastases, a single dosage of lexibulin (CYT-997) (7.5 mg/kg ip) dramatically decreased blood flow; this effect persisted six hours after treatment [1]. A mouse model of aggressive systemic myeloma showed a significant increase in survival with lexibulin (CYT-997) treatment (15 mg/kg/day) [2].
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| References |
[1]. Burns CJ, et al. CYT997: a novel orally active tubulin polymerization inhibitor with potent cytotoxic and vascular disrupting activity in vitro and in vivo. Mol Cancer Ther. 2009 Nov;8(11):3036-45.
[2]. Monaghan K, et al. CYT997 causes apoptosis in human multiple myeloma. Invest New Drugs. 2011 Apr;29(2):232-8. [3]. Ya Cao, wt al. Mitochondrial ROS Accumulation Inhibiting JAK2/STAT3 Pathway Is a Critical Modulator of CYT997-induced Autophagy and Apoptosis in Gastric Cancer. J Exp Clin Cancer Res. 2020 Jun 23;39(1):119. |
| Molecular Formula |
C₂₄H₃₂CL₂N₆O₂
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|---|---|
| Molecular Weight |
507.46
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| CAS # |
917111-49-0
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| Related CAS # |
Lexibulin;917111-44-5
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| SMILES |
CCC[C@H](NC1=C(C)C=NC(C2=CC=C(NC(NCC)=O)C(OC)=C2)=N1)C3=CN=CC=C3.[H]Cl.[H]Cl
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9706 mL | 9.8530 mL | 19.7060 mL | |
| 5 mM | 0.3941 mL | 1.9706 mL | 3.9412 mL | |
| 10 mM | 0.1971 mL | 0.9853 mL | 1.9706 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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