| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Tubulysin targets tubulin, the protein subunit of microtubules that form the cytoskeleton and mitotic spindle. By binding to tubulin, Tubulysin disrupts microtubule polymerization and dynamics, ultimately leading to cell cycle arrest and apoptosis in rapidly dividing cells. As a potent microtubule destabilizer, Tubulysin is an anti-microtubule toxin that exhibits effective IC50 concentrations in the picomolar range against multidrug-resistant cancer cell lines. This mechanism of action is similar to that of other tubulin-targeting agents such as the auristatins and maytansinoids.
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| ln Vitro |
In vitro, Tubulysin demonstrates potent cytotoxic activity against a wide range of cancer cell lines, with effective IC50 concentrations in the picomolar range. The compound exhibits activity against multidrug-resistant cancer cell lines, making it a valuable tool for studying mechanisms of drug resistance and developing strategies to overcome it. Tubulysin's potent antimitotic activity is attributed to its ability to bind to tubulin and disrupt microtubule polymerization and dynamics, leading to cell cycle arrest and apoptosis in rapidly dividing cells.
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| ln Vivo |
In vivo, Tubulysin 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 an ideal candidate for incorporation into small active molecule conjugate (SMDC) delivery systems and ADC synthesis. Due to its severe toxicity as a free drug, Tubulysin's therapeutic utility is realized through targeted delivery via ADCs or SMDCs.
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| Enzyme Assay |
Receptor binding or enzyme activity assays for Tubulysin are performed using purified tubulin protein. The binding of Tubulysin 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 on tubulin polymerization is measured spectrophotometrically by monitoring the turbidity of microtubule formation. Tubulysin 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 are performed using cancer cell lines, including multidrug-resistant lines. Cells are cultured in appropriate media and treated with Tubulysin 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 against cancer cells.
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| Animal Protocol |
In vivo studies with Tubulysin are typically conducted using Tubulysin-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 to tumor cells, minimizing systemic toxicity. Pharmacokinetic parameters are determined from plasma samples collected at various time points. Tubulysin's severe toxicity as a free drug necessitates targeted delivery approaches.
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| ADME/Pharmacokinetics |
Tubulysin 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 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 as a free drug are limited.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for Tubulysin 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'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 | |
| Additional Infomation |
Tubulysin is a family of potent cytotoxic peptides originally isolated from myxobacteria. These compounds are potent microtubule destabilizers with effective IC50 concentrations in the picomolar range against multidrug-resistant cancer cell lines. Due to their high potency, Tubulysins have attracted significant interest as payloads in antibody-drug conjugates (ADCs) for targeted cancer therapy. Tubulysin is also an ideal candidate for incorporation into small active molecule conjugate (SMDC) delivery systems. The compound is for research purposes only.
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| Exact Mass |
841.465
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|---|---|
| CAS # |
1943604-24-7
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| PubChem CID |
52945681
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| Appearance |
White to off-white solid powder
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| LogP |
5.4
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
12
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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)C)C[C@H](C)C(=O)O)OC(=O)C)C(C)C)NC(=O)[C@H]3CCCCN3C
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| InChi Key |
DLKUYSQUHXBYPB-NSSHGSRYSA-N
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| InChi Code |
InChI=1S/C44H67N5O9S/c1-11-29(7)39(47-41(53)35-14-12-13-19-48(35)10)43(54)49(25-57-38(51)20-26(2)3)36(27(4)5)23-37(58-31(9)50)42-46-34(24-59-42)40(52)45-33(21-30(8)44(55)56)22-32-17-15-28(6)16-18-32/h15-18,24,26-27,29-30,33,35-37,39H,11-14,19-23,25H2,1-10H3,(H,45,52)(H,47,53)(H,55,56)/t29-,30-,33+,35+,36+,37+,39-/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]-2-methyl-5-(4-methylphenyl)pentanoic 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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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.) |
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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