| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Tubulin
Indibulin targets tubulin, a key protein involved in cell division, and acts as a microtubule destabilizer. It binds to a site on tubulin that is distinct from the taxane- or Vinca alkaloid-binding sites. By binding to tubulin, it inhibits tubulin polymerization, which disrupts the mitotic spindle formation necessary for cell division. This disruption activates mitotic checkpoint proteins Mad2 and BubR1, induces mitotic arrest, and ultimately leads to apoptosis. |
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| ln Vitro |
Indibulin (300-2100 nM; 48 hours) has an IC50 of 150 nM, which inhibits the growth of MCF-7 cells.
Indibulin (300, 600 nM; 48 hours) inhibits G2/M phase cells, suggesting that it prevents the cell cycle from progressing during mitosis[1]. Indibulin (150-600 nM; 24 hours) causes MCF-7 cells to undergo apoptosis[1]. When Indibulin (150-600 nM; 48 hours) at concentrations of 300 and 600 nM is used to treat MCF-7 cells, it produces cleaved fragments of the PARP protein[1]. Indibulin demonstrates potent antitumor activity in vitro. It blocks tubulin polymerization with an IC50 of 0.3 μM. The compound blocks cell cycle progression at metaphase and displays antitumor activity against a variety of malignancies in vitro, with IC50 values ranging from 0.036 to 0.285 μM. It inhibits the proliferation of a wide range of cancer cell lines, including A-375, BT-474, DU-145, HT-29, MCF7, PC-3, A549, and HepG2, among others. |
| ln Vivo |
Indibulin induces complete tumor remission in the Yoshida AH13 rat sarcoma model in vivo. It displays oral availability and efficacy towards multidrug-resistant (MDR) tumor cells. In preclinical studies, the compound has demonstrated potent anticancer activity with minimal neurotoxicity. It has been evaluated in early clinical trials for the treatment of advanced solid tumors.
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| Enzyme Assay |
The in vitro enzyme assay for Indibulin involves measuring its ability to inhibit tubulin polymerization. In this cell-free system, purified tubulin is incubated with the compound, and the extent of polymerization is measured spectrophotometrically. The IC50 of 0.3 μM is determined from dose-response curves. Binding affinity to tubulin is assessed to confirm the compound’s interaction with its target.
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| Cell Assay |
Cell Line: MCF-7 cells
Concentration: 300, 600, 900, 1200, 1500, 1800, 2100 nM Incubation Time: 48 hours Result: Inhibited the proliferation of MCF-7 cells with an IC50 of 150 nM. In vitro cellular experiments involve treating cancer cell lines with Indibulin at concentrations typically ranging from 150 to 600 nM for 48 hours. Cell cycle analysis is performed using flow cytometry to assess the accumulation of cells in the G2/M phase, indicating mitotic arrest. Apoptosis is evaluated by assessing the activation of mitotic checkpoint proteins Mad2 and BubR1 and measuring markers of cell death. |
| Animal Protocol |
In vivo animal experiments have been conducted using the Yoshida AH13 rat sarcoma model, where oral administration of Indibulin induced complete tumor remission. The compound has also been evaluated in various human tumor xenograft models in mice to assess its antitumor efficacy and pharmacokinetic properties. These studies typically involve daily oral dosing and monitoring of tumor growth inhibition.
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| ADME/Pharmacokinetics |
Indibulin is orally available. A Phase I dose-finding and pharmacokinetic trial of orally administered Indibulin has been conducted in patients with advanced solid tumors. The compound has a molecular weight of 389.83 g/mol and a molecular formula of C22H16ClN3O2. It is soluble in DMSO but not in water.
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| Toxicity/Toxicokinetics |
Indibulin has a favorable toxicity profile compared to traditional tubulin-targeting agents, with significantly reduced neurotoxicity. This is due to its ability to discriminate between mature neuronal and nonneuronal tubulin. The compound has been evaluated in Phase I clinical trials, where its safety and tolerability were assessed in patients with advanced solid tumors.
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| References | |
| Additional Infomation |
Indibulin is a synthetic small molecule with antimitotic and potential antitumor activity. Indibulin binds to a site on microtubules that differs from the binding sites of taxanes or vinca alkaloids, thereby disrupting microtubule polymerization and inducing cell cycle arrest and apoptosis in tumor cells. This drug has been shown to be effective against multidrug-resistant (MDR) and taxane-resistant tumor cell lines.
Drug indications Investigations are underway for the treatment of solid tumors. Indibulin is a novel microtubule inhibitor that binds to a distinct site on tubulin, different from taxanes and vinca alkaloids, which helps overcome drug resistance. Its reduced neurotoxicity makes it a promising candidate for cancer therapy. It has undergone Phase I clinical trials for the treatment of advanced solid tumors. The compound is also known as ZIO-301 and D-24851. |
| Molecular Formula |
C22H16CLN3O2
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|---|---|
| Molecular Weight |
389.83
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| Exact Mass |
389.093
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| Elemental Analysis |
C, 67.78; H, 4.14; Cl, 9.09; N, 10.78; O, 8.21
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| CAS # |
204205-90-3
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| Related CAS # |
204205-90-3
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| PubChem CID |
2929
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| Appearance |
Off-white to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.665
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| LogP |
4.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
558
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C2C(=C1)C(=CN2CC3=CC=C(C=C3)Cl)C(=O)C(=O)N=C4C=CNC=C4
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| InChi Key |
SOLIIYNRSAWTSQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H16ClN3O2/c23-16-7-5-15(6-8-16)13-26-14-19(18-3-1-2-4-20(18)26)21(27)22(28)25-17-9-11-24-12-10-17/h1-12,14H,13H2,(H,24,25,28)
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| Chemical Name |
2-[1-[(4-chlorophenyl)methyl]indol-3-yl]-2-oxo-N-pyridin-4-ylacetamide
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| Synonyms |
ZIO-301; ZINC01996564; ZERO/005632; D-24851; d-24851; NCGC00160428-01
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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: 40~50 mg/mL (102.6~128.3 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (5.34 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.34 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 | 2.5652 mL | 12.8261 mL | 25.6522 mL | |
| 5 mM | 0.5130 mL | 2.5652 mL | 5.1304 mL | |
| 10 mM | 0.2565 mL | 1.2826 mL | 2.5652 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00591890 | Completed | Drug: indibulin | Advanced Cancer | Alaunos Therapeutics | October 2007 | Phase 1 |
| NCT00591136 | Completed | Drug: indibulin | Solid Tumors | Alaunos Therapeutics | April 2003 | Phase 1 |
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