| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| 25mg |
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| 50mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
DPP-4
Talabostat targets dipeptidyl peptidase IV (DPP-IV), DPP8, DPP9, fibroblast activation protein (FAP), and other DASH family enzymes. It competitively inhibits the catalytic sites of FAP and CD26/DPP-IV through high-affinity boron-serine interactions. |
|---|---|
| ln Vitro |
Talabostat mesylate (Val-boroPro mesylate) inhibits dipeptidyl peptidases, like FAP, by cleaving N-terminal Xaa-Pro or Xaa-Ala residues. This leads to the stimulation of cytokine and chemokine production, as well as specific T-cell immunity and T-cell dependent activity[3].
Talabostat mesylate (Val-boroPro mesylate) interacts with the catalytic site with high affinity and competitively inhibits the dipeptidyl peptidase (DPP) activity of FAP and CD26/DPP-IV[4]. In vitro, talabostat mesylate inhibits DPP-IV with an IC50 < 4 nM and a Ki of 0.18 nM. It inhibits DPP8 (IC50 = 4 nM; Ki = 1.5 nM) and DPP9 (IC50 = 11 nM; Ki = 0.76 nM). |
| ln Vivo |
Talabostat mesylate (Val-boroPro mesylate) can elicit immune responses from the innate and adaptive branches of the immune system against tumors.
Talabostat mesylate, also known as Val-boroPro mesylate, induces tumor regression and rejection in the WEHI 164 fibrosarcoma, EL4, and A20/2J lymphoma models. Tumor-specific CTL and memory immunity seem to play a role in the antitumor effect. Talabostat mesylate (Val-boroPro mesylate) treatment of the WEHI 164-inoculated mice results in an increase in the mRNA expression of cytokines and chemokines that are known to support T-cell priming and innate effector cell and T cell chemoattraction[4]. In vivo, talabostat mesylate stimulates both the innate and adaptive branches of the immune system. It has antitumor and hematopoietic stimulating activities. It is being evaluated for its potential in cancer immunotherapy. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for talabostat typically involve evaluating its inhibitory activity against purified DPP-IV, DPP8, DPP9, or FAP using fluorometric or chromogenic assays. IC50 and Ki values are determined by measuring residual enzyme activity.
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| Cell Assay |
For in vitro cell-based assays, talabostat mesylate is dissolved in DMSO or aqueous buffers and applied to cultured immune cells or cancer cells at concentrations ranging from 1 nM to 10 µM. Effects on cell proliferation, immune activation, or cytokine production are assessed after 24-72 hours of treatment.
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| Animal Protocol |
Mice: BLM (0.5mg/kg/day) is injected into male mice's nostrils on days -7, -6, -5, -2, -1, and 0. From day 1 to day 14, talabostat (40 µg/mouse) or vehicle (0.9% NaCl) is dosed twice a day. MRIs are done on days 0, 7, and 14 as well as prior to BLM. The animals are put to sleep after the final MRI scan, and their lungs are taken out for histology and quantitative real-time polymerase chain reaction (qRT-PCR) analysis[4].
In vivo animal studies commonly use mouse tumor models. Talabostat mesylate is administered orally at doses ranging from 0.1-10 mg/kg. Anti-tumor efficacy and immune activation are evaluated by measuring tumor growth, immune cell infiltration, and cytokine levels. |
| ADME/Pharmacokinetics |
Talabostat mesylate is orally active. It has a molecular weight of 310.18 g/mol. It is soluble in DMSO and aqueous buffers.
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| Toxicity/Toxicokinetics |
Talabostat mesylate has a manageable toxicity profile. Toxicity caused by DPP8/9 inhibition has been observed with non-selective DPP-IV inhibitors.
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| References |
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| Additional Infomation |
Talabostharol mesylate is an orally administered small molecule drug in its mesylate form, possessing antitumor and hematopoietic stimulating activities. Talabostharol inhibits dipeptidyl peptidases (such as fibroblast activating protein (FAP)) by cleaving N-terminal Xaa-Pro or Xaa-Ala residues, thereby stimulating the production of cytokines and chemokines and enhancing specific T-cell immunity and T-cell-dependent activity. This drug may also stimulate the production of colony-stimulating factors (such as granulocyte colony-stimulating factor (G-CSF)), thus promoting hematopoiesis. Dipeptidyl peptidases are involved in the activation of polypeptide hormones and chemokines.
Talabostat mesylate is a clinical-stage compound with antitumor and hematopoietic stimulating activities. It is being evaluated for cancer immunotherapy. Its mechanism of action involves inhibition of serine proteases involved in immune regulation. |
| Molecular Formula |
C10H23BN2O6S
|
|---|---|
| Molecular Weight |
310.17
|
| Exact Mass |
310.136
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| Elemental Analysis |
C, 50.50; H, 8.95; B, 5.05; N, 13.09; O, 22.42
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| CAS # |
150080-09-4
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| Related CAS # |
Talabostat isomer mesylate;Talabostat;149682-77-9
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| PubChem CID |
11522448
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| Appearance |
White to off-white solid powder
|
| LogP |
0.615
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
20
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| Complexity |
328
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
S(C([H])([H])[H])(=O)(=O)O[H].O=C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])[H])N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])B(O[H])O[H]
|
| InChi Key |
OXYYOEIGQRXGPI-WSZWBAFRSA-N
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| InChi Code |
InChI=1S/C9H19BN2O3.CH4O3S/c1-6(2)8(11)9(13)12-5-3-4-7(12)10(14)15;1-5(2,3)4/h6-8,14-15H,3-5,11H2,1-2H3;1H3,(H,2,3,4)/t7-,8-;/m0./s1
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| Chemical Name |
[(2R)-1-[(2S)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid;methanesulfonic acid
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| Synonyms |
Talabostat; BXCL701; BXCL-701; BXCL 701; Val-boro-pro; PT-100; PT100, PT 100; D05989
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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: Please store this product in a sealed and protected environment, 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) |
H2O: ~250 mg/mL (~806 mM)
DMSO: ≥ 40 mg/mL (~129 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.06 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 (8.06 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 (8.06 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (322.39 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Solubility in Formulation 5: 50 mg/mL (161.20 mM) in Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2240 mL | 16.1202 mL | 32.2404 mL | |
| 5 mM | 0.6448 mL | 3.2240 mL | 6.4481 mL | |
| 10 mM | 0.3224 mL | 1.6120 mL | 3.2240 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 |
| NCT04171219 | Active Recruiting |
Biological: Pembrolizumab Drug: Talabostat Mesylate |
Advanced Malignant Solid Neoplasm Recurrent Malignant Solid Neoplasm |
M.D. Anderson Cancer Center | March 19, 2020 | Phase 2 |
| NCT00303940 | Completed | Drug: carboplatin Drug: talabostat mesylate |
Kidney Cancer Liver Cancer |
National Institutes of Health Clinical Center (CC) |
December 2005 | Phase 1 |
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