| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Tubulysin A targets tubulin, the protein subunit of microtubules that form the cytoskeleton and mitotic spindle. By binding to tubulin, Tubulysin A disrupts microtubule dynamics and inhibits cell division. The compound inhibits polymerization more efficiently than vinblastine and induces depolymerization of isolated microtubules. This mechanism leads to cell cycle arrest in the G2/M phase and subsequent apoptosis in rapidly dividing cancer cells. As an anti-microtubule toxin, Tubulysin A functions similarly to other tubulin-targeting agents such as auristatins and maytansinoids.
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| ln Vitro |
In vitro, Tubulysin A demonstrates potent antiproliferative activity against a wide range of cancer cell lines. The compound inhibits tubulin polymerization more efficiently than vinblastine and induces depolymerization of isolated microtubules. Tubulysin A arrests cells in the G2/M phase of the cell cycle and acts as an inducer of apoptosis. Its extreme potency makes it an ideal candidate for incorporation into antibody-drug conjugates (ADCs) as a cytotoxic payload for targeted cancer therapy.
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| ln Vivo |
In vivo, Tubulysin A has attracted significant interest as a payload in antibody-drug conjugates (ADCs) for targeted cancer therapy. The compound's extreme potency and ability to kill cancer cells at picomolar concentrations make it suitable for ADC development. Due to its severe toxicity as a free drug, Tubulysin A's therapeutic utility is realized through targeted delivery via ADCs or small active molecule conjugate (SMDC) delivery systems. Detailed in vivo efficacy data for Tubulysin A as a free agent are limited, as it is primarily used as a cytotoxic payload in targeted delivery systems.
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| Enzyme Assay |
Receptor binding or enzyme activity assays for Tubulysin A are performed using purified tubulin protein. The binding of Tubulysin A to tubulin is assessed using methods such as fluorescence polarization, surface plasmon resonance (SPR), or competition binding assays with labeled tubulin-binding agents. Alternatively, the effect of Tubulysin A on tubulin polymerization is measured spectrophotometrically by monitoring the turbidity of microtubule formation. Tubulysin A is incubated with tubulin at varying concentrations in polymerization buffer, and the extent of polymerization is measured at 340 nm. IC50 values for inhibition of polymerization are calculated from concentration-response curves.
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| Cell Assay |
Cellular assays for Tubulysin A are performed using cancer cell lines, including multidrug-resistant lines. Cells are cultured in appropriate media and treated with Tubulysin A at varying concentrations for defined time periods. Cell viability and proliferation are assessed using standard assays such as MTT, CellTiter-Glo, or colony formation assays. Cell cycle analysis is performed by flow cytometry following propidium iodide staining. Apoptosis is assessed by measuring caspase activation, PARP cleavage, or Annexin V staining. The picomolar IC50 values demonstrate the extreme potency of Tubulysin A against cancer cells.
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| Animal Protocol |
In vivo studies with Tubulysin A are typically conducted using Tubulysin A-based ADCs or SMDCs in mouse xenograft models of cancer. The ADC or SMDC is administered via intravenous injection at defined doses and schedules. Tumor growth is monitored by caliper measurements, and tumor volumes are calculated. The targeted delivery system allows for the selective delivery of Tubulysin A to tumor cells, minimizing systemic toxicity. Pharmacokinetic parameters are determined from plasma samples collected at various time points. Tubulysin A's severe toxicity as a free drug necessitates targeted delivery approaches.
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| ADME/Pharmacokinetics |
Tubulysin A has a molecular weight of 842.10 and a molecular formula of C44H67N5O9S. The compound is a potent microtubule destabilizer with activity in the picomolar range. As a free drug, Tubulysin A has limited therapeutic utility due to severe toxicity. The compound is therefore ideal for incorporation into small active molecule conjugate (SMDC) delivery systems and is commonly used in ADC synthesis as a cytotoxic payload. Detailed pharmacokinetic data for Tubulysin A as a free drug are limited.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for Tubulysin A as a free drug are limited due to its severe toxicity. The compound is intended for research use only and is not approved for human therapeutic applications as a free drug. Tubulysin A's extreme potency requires careful handling and appropriate safety precautions. The compound is used as a payload in ADCs and SMDCs for targeted cancer therapy research. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment.
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| References |
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| Additional Infomation |
Tubulysin A is a diester and carboxylic acid. It has been reported that Archangium gephyra contains Tubulysin A, and relevant data is available for reference.
Tubulysin A is a naturally occurring tetrapeptide originally isolated from myxobacteria that functions as a potent anti-microtubule agent. It inhibits tubulin polymerization more efficiently than vinblastine and induces depolymerization of isolated microtubules, arresting cells in the G2/M phase and inducing apoptosis. Due to its high potency, Tubulysin A has attracted significant interest as a payload in antibody-drug conjugates (ADCs) for targeted cancer therapy. The compound is for research purposes only and is not approved for clinical use. |
| Molecular Formula |
C43H65N5O10S
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|---|---|
| Molecular Weight |
844.068700000001
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| Exact Mass |
843.445
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| CAS # |
205304-86-5
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| PubChem CID |
12134544
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| Appearance |
White to light yellow solid powder
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| LogP |
7.063
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
24
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| Heavy Atom Count |
59
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| Complexity |
1390
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| Defined Atom Stereocenter Count |
7
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| SMILES |
CC[C@H](C)[C@@H](C(=O)N(COC(=O)CC(C)C)[C@H](C[C@H](C1=NC(=CS1)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C[C@H](C)C(=O)O)OC(=O)C)C(C)C)NC(=O)[C@H]3CCCCN3C
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| InChi Key |
IBEDDHUHZBDXGB-OEJISELMSA-N
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| InChi Code |
InChI=1S/C43H65N5O10S/c1-10-27(6)38(46-40(53)34-13-11-12-18-47(34)9)42(54)48(24-57-37(51)19-25(2)3)35(26(4)5)22-36(58-29(8)49)41-45-33(23-59-41)39(52)44-31(20-28(7)43(55)56)21-30-14-16-32(50)17-15-30/h14-17,23,25-28,31,34-36,38,50H,10-13,18-22,24H2,1-9H3,(H,44,52)(H,46,53)(H,55,56)/t27-,28-,31+,34+,35+,36+,38-/m0/s1
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| Chemical Name |
(2S,4R)-4-[[2-[(1R,3R)-1-acetyloxy-4-methyl-3-[3-methylbutanoyloxymethyl-[(2S,3S)-3-methyl-2-[[(2R)-1-methylpiperidine-2-carbonyl]amino]pentanoyl]amino]pentyl]-1,3-thiazole-4-carbonyl]amino]-5-(4-hydroxyphenyl)-2-methylpentanoic acid
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ~100 mg/mL (~118.47 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.96 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 (2.96 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (2.96 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1847 mL | 5.9237 mL | 11.8474 mL | |
| 5 mM | 0.2369 mL | 1.1847 mL | 2.3695 mL | |
| 10 mM | 0.1185 mL | 0.5924 mL | 1.1847 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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