Talabostat mesylate
IC50: 1 nM
Talabostat mesilate (PT-100; Val-boroPro) is an orally active, specific inhibitor of dipeptidyl peptidases for DPP4, including tumor-associated fibroblast activation protein- (FAP).
Fibroblast activation protein- (FAP), as an integral membrane serine protease and member of the post-prolyl peptidase family, closely related to dipeptidyl peptidase IV (DPPIV) and displays a DPPIV-like fold with the characteristic /-hydrolase and eightbladed -propeller domains [1].
In vitro: By the cleavage of N-terminal Xaa-Pro or Xaa-Ala residues, talabostat blocks dipeptidyl peptidases, such as fibroblast activation protein (FAP), resulting in inducing the production of cytokine and chemokine (besides specific T-cell immunity and T-cell-dependent activity). This agent may also induce the production of colony stimulating factors, for instance, granulocyte colony stimulating factor (G-CSF), resulting in the inducement of hematopoiesis. Dipeptidyl peptidases are referred to the activation of polypeptide hormones and chemokines.
Talabostat slightly lowered the growth rates of the FAP-expressing tumors but because PT-630 and LAF-237 did not, the growth blockade was likely not related to inhibit FAP or the related post-prolyl peptidase dipeptidyl peptidase IV.[1]
In vivo: So far, no study in vivo has been conducted.
Clinical trial: Clinical study has been conducted.
Reference:
[1]. Huang Y, Simms AE, Mazur A, Wang S, León NR, Jones B, Aziz N, Kelly T. Fibroblast activation protein-α promotes tumor growth and invasion of breast cancer cells through non-enzymatic functions. Clin Exp Metastasis. 2011 Aug;28(6):567-79.
- 1. Yeonhee Cho, Zhongzheng Cao, et al. "NLRP10 maintains epidermal homeostasis by promoting keratinocyte survival and P63-dependent differentiation and barrier function." Cell Death Dis. 2024 Oct 18;15(10):759. PMID: 39424623
- 2. Inga Szymanska, Stefan Bauernfried, et al. "Vaccinia virus F1L blocks the ribotoxic stress response to subvert ZAKα‐dependent NLRP1 inflammasome activation." Eur J Immunol. 2024 Jul 31:e2451135 PMID: 39086059
- 3. Xiaoyu Houa, Mingyang Liu, et al. "Differential releasing hydrogel loaded with oncolytic viruses and anti-CAFs drug to enhance oncology therapeutic efficacy." S1001-8417(24)00625-9
- 4. Christine Wolf, Hannah Fischer, et al. "Hemophagocytic lymphohistiocytosis–like hyperinflammation due to a de novo mutation in DPP9." J Allergy Clin Immunol. 2023 Aug 5;S0091-6749(23)00978-8. PMID: 37544411
- 5. Andreas Linder, Stefan Bauernfried, et al. "CARD8 inflammasome activation triggers pyroptosis in human T cells." EMBO J 2020 Aug 25;e105071. PMID:32840892
- 6. Chen M, Lei X, et al. "Pericyte-targeting prodrug overcomes tumor resistance to vascular disrupting agents." J Clin Invest. 2017 Oct 2;127(10):3689-3701. PMID:28846068
- 7. Feng X, Wang Q, et al. "A synthetic urinary probe-coated nanoparticles sensitive to fibroblast activation protein α for solid tumor diagnosis." Int J Nanomedicine. 2017 Jul 27;12:5359-5372. PMID:28794628
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 310.18 |
| Cas No. | 150080-09-4 |
| Formula | C10H23BN2O6S |
| Solubility | ≥11.45 mg/mL in DMSO; ≥31 mg/mL in H2O; ≥8.2 mg/mL in EtOH with ultrasonic |
| SDF | Download SDF |
| Canonical SMILES | OS(=O)(C)=O.O=C([C@H](C(C)C)N)N1[C@H](B(O)O)CCC1 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
MDA MB-435 cells and human breast cancer cell lines WTY-1 and WTY-6 |
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Preparation method |
This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
10 μM |
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Applications |
In MDA MB-231 cells that do not express FAP, Talabostat showed no effect in FAP activity assay. In WTY-1 and WTY-6 cells that express wild type and active FAP to high levels, Talabostat significantly inhibited FAP activity. |
| Animal experiment [1]: | |
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Animal models |
SCID mice bearing human breast cancer cell lines WTY-1 and WTY-6, as well as MDA MB-435 cells |
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Dosage form |
1.3 mg/kg; p.o.; q.d. |
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Applications |
In SCID mice bearing human breast cancer cell lines WTY-1 and WTY-6, as well as MDA MB-435 cells, Talabostat slightly slowed tumor growth. In mice bearing MDA MB-435 cells, Talabostat delayed production of measurable tumors by nearly 12 days, which however, was not statistically different. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Huang Y, Simms AE, Mazur A, Wang S, León NR, Jones B, Aziz N, Kelly T. Fibroblast activation protein-α promotes tumor growth and invasion of breast cancer cells through non-enzymatic functions. Clin Exp Metastasis. 2011 Aug;28(6):567-79. |
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Quality Control & MSDS
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