| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Valecobulin targets beta-tubulin, a key protein in the formation of microtubules. By inhibiting tubulin polymerization, it prevents the assembly of microtubules, which are essential for cell division and maintaining cell structure. This disruption leads to cell cycle arrest at the G2/M phase. Its primary mechanism as a vascular disrupting agent involves the rapid collapse of tumor blood vessels.
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| ln Vitro |
In vitro, Valecobulin demonstrates potent cytotoxicity against several cancer cell lines. Notably, it retains activity against P-glycoprotein (P-gp) overexpressing multidrug-resistant (MDR) positive cell lines such as HCT15. Treatment with the compound induces cell cycle arrest at the G2/M phase, which is associated with strong inhibition of tubulin polymerization.
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| ln Vivo |
In a number of human tumor xenograft models, valecobulin (5 mg/kg; i.p.; given on days 2, 6, 10, and 14; male BALB/C nu/nu mice) treatment showed a strong antitumor activity [1].
In vivo, Valecobulin shows significant antitumor efficacy. It is effective against both murine tumors (CT26 and 3LL) and human xenografts (HCT116 and HCT15) in mice. In a rabbit VX2 liver tumor model, treatment with Valecobulin (CKD516) at doses of 5, 9, or 12 mg/m² via intravenous injection resulted in a significantly smaller increase in tumor size compared to the control group. |
| Enzyme Assay |
Specific cell-free enzyme/receptor binding assay protocols for Valecobulin involve assessing its ability to inhibit tubulin polymerization. These assays typically use purified tubulin protein and measure the extent of polymerization spectrophotometrically in the presence of the compound. The inhibition of polymerization indicates that the compound is binding to tubulin and preventing its assembly into microtubules.
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| Cell Assay |
In vitro cell-based assays for Valecobulin use various cancer cell lines, including both drug-sensitive and multidrug-resistant (MDR) lines like HCT15. Cells are treated with the compound, and cell viability is assessed using standard cytotoxicity assays (e.g., MTT assay) to determine IC50 values. Cell cycle analysis by flow cytometry is used to confirm G2/M phase arrest.
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| Animal Protocol |
Animal/Disease Models: Male BALB/C nu/nu (nude) mice (5-6 weeks old) with HCT-116 or HCT-15 cells [1]
Doses: 5 mg/kg Route of Administration: intraperitoneal (ip) injection; 2nd and 6th , 10 and 14-day dosing Experimental Results: demonstrated significant anti-tumor efficacy in a variety of human tumor xenograft models. In vivo animal studies for Valecobulin have been performed in multiple models. In one study, VX2 liver tumor-bearing rabbits were given a single intravenous injection of Valecobulin at doses of 5, 9, or 12 mg/m². Tumor size was monitored to assess efficacy. In other studies, the compound was tested in mice bearing CT26, 3LL, HCT116, and HCT15 tumors to evaluate its antitumor activity. |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic properties of Valecobulin are not extensively reported in the provided literature. The compound has a molecular weight of 536.6 g/mol and a molecular formula of C26H28N6O5S. It is administered intravenously (i.v.) and is soluble in DMSO at 10 mM.
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| Toxicity/Toxicokinetics |
Specific toxicological data for Valecobulin are not detailed in the available literature. The compound is classified for research use only and is not intended for human therapeutic applications. As a vascular disrupting agent and tubulin inhibitor, its primary effects are related to its pharmacological activity on tumor vasculature and cell division.
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| References |
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| Additional Infomation |
Valecobulin is a benzophenone derivative and a water-soluble valine prodrug of the tubulin-binding agent S516, possessing potential tubulin inhibitory, angiogenic, and antitumor activities. After administration, valecobulin is converted to its active metabolite, S-516, which binds to tubulin, preventing tubulin polymerization in tumor vascular endothelial cells and tumor cells. This blocks the formation of the mitotic spindle, leading to cell cycle arrest at the G2/M phase. Therefore, the drug disrupts tumor blood vessels and blood flow, depriving tumor cells of nutrients and inducing tumor cell apoptosis. Furthermore, the drug also exerts direct cytotoxic effects on tumor cells by inhibiting tubulin polymerization.
Valecobulin (CAS 1188371-47-2) is a potent beta-tubulin polymerization inhibitor and a vascular disrupting agent (VDA). It is a valine prodrug of S516 and has demonstrated marked antitumor activity against murine and human solid tumors. The compound has shown efficacy in various in vivo models, including rabbit VX2 liver tumors and mouse xenografts. No clinical trial or approved indication data are available. |
| Molecular Formula |
C26H28N6O5S
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|---|---|
| Molecular Weight |
536.6027
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| Exact Mass |
536.184
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| CAS # |
1188371-47-2
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| Related CAS # |
S516;1016543-77-3;Valecobulin hydrochloride;1240321-53-2
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| PubChem CID |
44243402
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| Appearance |
White to off-white solid powder
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| LogP |
4.919
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
38
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| Complexity |
794
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC(C)[C@@H](C(=O)NC1=NC(=CS1)C2=CC(=C(C=C2)C(=O)C3=CC(=C(C(=C3)OC)OC)OC)N4C=NC=N4)N
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| InChi Key |
UKKRUIXIDCWALA-QFIPXVFZSA-N
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| InChi Code |
InChI=1S/C26H28N6O5S/c1-14(2)22(27)25(34)31-26-30-18(11-38-26)15-6-7-17(19(8-15)32-13-28-12-29-32)23(33)16-9-20(35-3)24(37-5)21(10-16)36-4/h6-14,22H,27H2,1-5H3,(H,30,31,34)/t22-/m0/s1
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| Chemical Name |
(2S)-2-amino-3-methyl-N-[4-[3-(1,2,4-triazol-1-yl)-4-(3,4,5-trimethoxybenzoyl)phenyl]-1,3-thiazol-2-yl]butanamide
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| HS Tariff Code |
2934.99.9001
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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 Vitro) |
DMSO : ~125 mg/mL (~232.95 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.88 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 20.8 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: ≥ 2.08 mg/mL (3.88 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 20.8 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 | 1.8636 mL | 9.3179 mL | 18.6359 mL | |
| 5 mM | 0.3727 mL | 1.8636 mL | 3.7272 mL | |
| 10 mM | 0.1864 mL | 0.9318 mL | 1.8636 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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