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| 5mg |
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| 25mg |
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Purity: ≥98%
CYT997 (also called Lexibulin; CYT-997; CYT 997) 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 |
Using the standard turbidimetric assay for tubulin polymerization, lexibulin (CYT-997) inhibits tubulin polymerization in vitro with an IC50 of approximately 3 μmol/L (compared with the half-maximal inhibitory concentration of 2 μmol/L for colchicine under identical conditions). Moreover, lexibulin can reversibly damage cells' microtubule networks, as demonstrated by fluorescence microscopy. Therefore, applying Lexibulin (1 μM) to A549 cells caused a rapid reorganization of microtubules, including the disintegration of the preexisting microtubule network and the build-up of tubulin in plaques within some cells' cytoplasm. Major changes in cell morphology, such as rounding of the cell and loss of adhesion, are visible after 24 hours. After receiving Lexibulin for an hour, the effects wear off quickly and the cells quickly revert to their original microtubule architecture. When considered collectively, the data suggest that lexibulin is a member of the class of anticancer drugs that damage tubulin-containing structures instead of stabilizing them. At 15 and 24 hours, respectively, cells treated with vehicle showed 15% and 19% of cells in G2-M phase; at the same time points, cells treated with 1 μM Lexibulin had 38% and 43% of cells in G2-M. Additionally, only 66% of all cells are in the G1, S, and G2-M phases 24 hours after Lexibulin treatment, which implies that cells blocked at the G2-M boundary are most likely driven towards apoptosis and cell death rather than exiting back to G1, as would be the case in a normal cell cycle[1]. Lexibulin potently inhibits proliferation, induces cell cycle arrest, and most importantly, causes apoptosis of both primary MM cells and human myeloma cell lines (HMCLs), all of which are consistent with the disruption of cellular tubulin[2].
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| ln Vivo |
Oral administration of Lexibulin (CYT-997) is started 13 days following cell implantation in a xenograft model utilizing the human prostate cancer cell line PC3, at which point palpable tumors were visible. With Lexibulin (CYT-997), there was a dosage-dependent reduction of tumor development that was comparable to parenterally administered paclitaxel at the highest dose. Blood flow in liver metastases was evidently reduced by a single dosage of Lexibulin (CYT-997) (7.5 mg/kg ip), and this reduction persisted for six hours after the dose[1]. Treatment with lexibulin (CYT-997) (15 mg/kg/day) prolongs survival in a mouse model of aggressive systemic myelomatosis significantly[2].
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| Animal Protocol |
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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 |
C24H30N6O2
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| Molecular Weight |
434.53
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| CAS # |
917111-44-5
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| Related CAS # |
Lexibulin dihydrochloride;917111-49-0
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| SMILES |
O(C([H])([H])[H])C1=C(C([H])=C([H])C(=C1[H])C1=NC([H])=C(C([H])([H])[H])C(=N1)N([H])[C@]([H])(C1=C([H])N=C([H])C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])[H])N([H])C(N([H])C([H])([H])C([H])([H])[H])=O
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| InChi Key |
MTJHLONVHHPNSI-IBGZPJMESA-N
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| InChi Code |
InChI=1S/C24H30N6O2/c1-5-8-19(18-9-7-12-25-15-18)28-22-16(3)14-27-23(30-22)17-10-11-20(21(13-17)32-4)29-24(31)26-6-2/h7,9-15,19H,5-6,8H2,1-4H3,(H2,26,29,31)(H,27,28,30)/t19-/m0/s1
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| Chemical Name |
(S)-1-ethyl-3-(2-methoxy-4-(5-methyl-4-((1-(pyridin-3-yl)butyl)amino)pyrimidin-2-yl)phenyl)urea
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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 Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.75 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.75 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3013 mL | 11.5067 mL | 23.0134 mL | |
| 5 mM | 0.4603 mL | 2.3013 mL | 4.6027 mL | |
| 10 mM | 0.2301 mL | 1.1507 mL | 2.3013 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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