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| [(2R)-1-[(2S)-2-Amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid mesylate Basic information |
| Product Name: | [(2R)-1-[(2S)-2-Amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid mesylate | | Synonyms: | [(2R)-1-[(2S)-2-Amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid mesylate;Boronic acid, ((2R)-1-((2S)-2-amino-3-methyl-1-oxobutyl)-2-pyrrolidinyl)-, monomethanesulfonate;Unii-V8zg4Y1B51;Methanesulfonic acid ((R)-1-((S)-2-amino-3-methyl-butanoyl)pyrrolidin-2-yl)boronic acid (1:1);Talabostat mesylate;Val-boroPro mesylate;CS-1219;Talabostat-mesylate, PT-100 | | CAS: | 150080-09-4 | | MF: | C10H23BN2O6S | | MW: | 310.17 | | EINECS: | | Product Categories: | | Mol File: | 150080-09-4.mol |
| [(2R)-1-[(2S)-2-Amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid mesylate Chemical Properties |
| Melting point | >160°C (dec.) | | storage temp. | under inert gas (nitrogen or Argon) at 2–8 °C | | solubility | Soluble in DMSO (up to at least 25 mg/ml) | | form | solid | | color | White | | Stability: | Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month. |
| [(2R)-1-[(2S)-2-Amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid mesylate Usage And Synthesis |
| Description | Talabostat is a non-selective inhibitor of dipeptidyl peptidases (DPPs), including DPP-4, DPP-7, DPP-8, DPP-9, fibroblast activation protein (FAP), and prolyl endopeptidase (PREP; IC50s = >4, 310, 4, 11, 560, and 390 nM, respectively). It inhibits proliferation of superantigen-stimulated human peripheral blood mononuclear cells (PBMCs; IC50 = ~10 nM). Talabostat (5 μg twice per day) increases expression of a variety of cytokines, including those encoding IL-1β, IL-6, and G-CSF, and chemokines in tumors and tumor-draining lymph nodes in a WEHI-164 fibrosarcoma mouse model. It reduces tumor growth in WEHI-164, MM45T.Sp, and MM52.T fibrosarcoma, EL-4 and A20/2J lymphoma, B16/F10 melanoma, and P815 mastocytoma syngeneic mouse models. Talabostat also increases the efficacy of the antitumor antibodies rituximab and trastuzumab in Namalwa B cell lymphoma and LS180 colon carcinoma mouse xenograft models, respectively. | | Uses | Treatment of cancer; hematopoetic stimulant. | | Uses | Talabostat Mesylate can be used in biological study and pharmacological activity of treatment of cancer using immunomodulation. | | General Description | A prolineboronic acid-based broad-spectrum DDP IV activity and/or structural homologue (DASH) family dipeptidyl peptidases inhibitor that converts in solution between the protonated active form and a cyclized inactive form due to a reversible intramolecular B-N dative bond formation of the non-protonated Val-boroPro (kinact = 6.4 x 10--4 s- and kcyc = 6.4 x 10-5 s- at pH 7.8). Although equilibrium favors cyclization at basic pH, high affinity binding (kon & koff toward CD26 at pH 7.8 = 5.02 x 106 M-s- and 77.8 x 10-6 s-, respectively) drives the equilibrium away from cyclization and traps the active form in enzyme-bound state with prolonged incubation. Reported to inhibit DPP7/DPPII/QPP (IC50/[Substrate]/rxn time at pH 5.5 = 15 nM/500 μM Lys-Pro-MNA/1 h & 310 nM/50 μM Nle-Pro-AMC/15 min), CD26/DPPIV (IC50 = 26 nM; 500 μM Ala-Pro-MNA for 1 h at pH 7.8), fibroblast activation protein/FAP (IC50 = 40 nM; 250 μM Ala-Pro-AFC at pH 2.0), DPP8 (IC50 = 4 nM; 100 μM Ala-Pro-AFC for 15 min at pH 8.0), DDP9 (IC50 = 11 nM; 100 μM Gly-Pro-AMC for 30 min at pH 7.4) with little potency against 9 other proteases (IC50 >100 μM; aminopeptidase P, chymoptrypsin, leukocyte elastase, plasma kallikrein, plasmin, prolidase, thrombin, trypsin, tryptase), while contradictory reports regarding prolyl endopeptidase/PEP/PREP inhibition exist (e.g. IC50 = 390 nM/50 μM Z-Gly-Pro-AMC/pH 7.5/30 min vs. 25 μM/500 μM Z-Gly-Pro-MNA/pH 7.8/60 min). Shown to promote the propagation of human BM CD34+ cells by stimulating stromal cells cytokine production in vitro (min EC 0.1 nM) and display hematopoietic stimulatory effect in mice in vivo (min ED 2 μg/mouse/12 h; p.o.). Although orally available in mice and rats, caution must be taken not to exceed toxicity levels (MTD = 25 μg/mL using Sprague-Dawley rats; LD50 ~0.5 mg/mL in 24 survival test using Fisher rats; p.o.) for in vivo studies. | | Biochem/physiol Actions | Cell permeable: yes | | 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. | | IC 50 | 1 nm | | References | 1) Lankas et al. (2005) Dipeptidyl Peptidase IV Inhibition for the Treatment of Type 2 Diabetes; Diabetes 54 2988
2) Adams et al. (2004) PT-100,a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism; Cancer Res. 64 5471
3) Walsh et al. (2013) Val-BoroPro Accelerates T Cell Priming via Modulation of Dendritic Cell Trafficking Resulting in Complete Regression of Established Murine Tumors; PLoS One 8 e58860
4) Okondo et al. (2017) DPP8/9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis; Nat. Chem. Biol. 13 46
5) Okondo et al. (2018) Inhibition of DPP8/9 Activates the Nlrp1b Inflammasome; Cell Chem. Biol. 25 1 |
| [(2R)-1-[(2S)-2-Amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid mesylate Preparation Products And Raw materials |
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