| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Ki: 0.18 nM (DPP-IV), 1.5 nM (DPP8), 0.76 nM (DPP9)[1]
The primary targets of Talabostat are dipeptidyl peptidases (DPPs), particularly DPP-IV, DPP8, and DPP9. It acts as a nonselective inhibitor with an IC50 < 4 nM for DPP-IV and a Ki of 0.18 nM. It also inhibits fibroblast activation protein (FAP). By inhibiting these enzymes, it modulates immune responses and induces cytokine production. |
|---|---|
| ln Vitro |
Talabostat (Val-boroPro) inhibits dipeptidyl peptidases, like FAP, by cleaving the N-terminal Xaa-Pro or Xaa-Ala residues. This stimulates the synthesis of cytokines and chemokines, as well as specific T-cell immunity and T-cell reliant activity[3]. Talabostat (Val-boroPro) interacts with the catalytic region with high affinity and competitively inhibits the dipeptidyl peptidase (DPP) activity of FAP and CD26/DPP-IV[4].
In vitro, Talabostat inhibits DPP-IV, DPP8, and DPP9 with high potency (IC50 < 4 nM for DPP-IV). It induces cytokine and chemokine production in monocytes and macrophages. It stimulates T-cell proliferation and enhances immune responses. It also inhibits FAP, which is expressed in tumor stroma. |
| ln Vivo |
Both the innate and adaptive immune systems' tumor-fighting capabilities can be enhanced by talabostat (Val-boroPro; PT100). Talabostat (Val-boroPro), in the WEHI 164 fibrosarcoma and EL4 and A20/2J lymphoma models, induces tumor regression and rejection. It seems that protective immune memory and tumor-specific CTL are involved in the anticancer impact. Treatment with talabostat (Val-boroPro) increases the mRNA expression of cytokines and chemokines in WEHI 164-inoculated mice, which are known to facilitate T-cell priming and chemoattraction of T cells and innate effector cells[4].
In vivo, Talabostat stimulates innate immunity and induces cytokine production in animal models. It exhibits antitumor activity in various tumor models, including melanoma and colon cancer. It is orally active and enhances the efficacy of chemotherapy. Its immunomodulatory effects contribute to its anticancer activity. |
| Enzyme Assay |
For DPP enzyme inhibition assays, recombinant DPP-IV, DPP8, or DPP9 is incubated with a fluorogenic substrate in the presence of Talabostat. Enzyme activity is measured by fluorescence release. IC50 values are determined from dose-response curves. FAP inhibition is assessed using a similar assay.
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| Cell Assay |
For cellular assays, monocytes or macrophages are treated with Talabostat. Cytokine and chemokine levels in culture supernatants are measured by ELISA. T-cell proliferation is assessed by [3H]thymidine incorporation. DPP activity in cell lysates is measured using fluorogenic substrates.
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| Animal Protocol |
Mice: BLM (0.5mg/kg/day) is administered on days -7, -6, -5, -2, -1, 0 in the nostrils of male mice. Talabostat (40 μg/mouse) or vehicle (0.9% NaCl) is dosed per os twice daily from day 1-14. MRI is performed before BLM and at days 0, 7 and 14. After the last MRI acquisition, animals are euthanised and the lungs harvested for histological and quantitative real-time polymerase chain reaction (qRT-PCR) analyses[4].
For in vivo studies, tumor-bearing mice receive Talabostat orally at various doses. Tumor volume is measured twice weekly. Cytokine levels in serum and tumor tissue are measured by ELISA. Immune cell populations in spleen and tumor are analyzed by flow cytometry. Survival is monitored. |
| References |
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| Additional Infomation |
Talabostat is a small molecule drug with antitumor and hematopoietic stimulating activities. It stimulates the production of cytokines and chemokines and enhances specific T-cell immunity and T-cell-dependent activity by cleaving N-terminal Xaa-Pro or Xaa-Ala residues, thereby inhibiting dipeptidyl peptidases (such as fibroblast activation protein (FAP)). Furthermore, this drug may 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.
See also: Talabostat mesylate (note moved to). Drug Indications It has been investigated for the treatment of lymphoma (non-Hodgkin lymphoma), leukemia (lymphoid), lung cancer, melanoma, and pancreatic cancer. |
| Molecular Formula |
C9H19BN2O3
|
|---|---|
| Molecular Weight |
214.07
|
| Exact Mass |
214.148
|
| CAS # |
149682-77-9
|
| Related CAS # |
Talabostat mesylate;150080-09-4;Talabostat isomer mesylate
|
| PubChem CID |
6918572
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| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.2±0.1 g/cm3
|
| Boiling Point |
421.4±55.0 °C at 760 mmHg
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| Flash Point |
208.7±31.5 °C
|
| Vapour Pressure |
0.0±2.3 mmHg at 25°C
|
| Index of Refraction |
1.514
|
| LogP |
0.01
|
| tPSA |
86.79
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
15
|
| Complexity |
235
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CC(C)[C@H](N)C(N1[C@H](B(O)O)CCC1)=O
|
| InChi Key |
FKCMADOPPWWGNZ-YUMQZZPRSA-N
|
| InChi Code |
InChI=1S/C9H19BN2O3/c1-6(2)8(11)9(13)12-5-3-4-7(12)10(14)15/h6-8,14-15H,3-5,11H2,1-2H3/t7-,8-/m0/s1
|
| Chemical Name |
((R)-1-(L-Valyl)pyrrolidin-2-yl)boronic acid
|
| Synonyms |
PT100 Val-boroPro PT-100 Talabostat
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ≥ 40 mg/mL (~186.85 mM)
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.6714 mL | 23.3568 mL | 46.7137 mL | |
| 5 mM | 0.9343 mL | 4.6714 mL | 9.3427 mL | |
| 10 mM | 0.4671 mL | 2.3357 mL | 4.6714 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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