Val-boroPro - NLRP1 Inflammasome Inducer, DPP8/9 inhibitor

Dipeptide boronic acid

ABOUT

NLRP1 inflammasome inducer

Val-boroPro (VbP, Talabostat), a dipeptide boronic acid, is a non-selective inhibitor of various dipeptidyl peptidases (DPPs) including DPP4, DPP8 and DPP9 [1]. It exhibits immunostimulatory properties, notably by disrupting the inhibitory interaction between DPP8/9 and the inflammasome sensor NLRP1 (NLR family member, pyrin domain containing 1). Hence, VbP is a potent inducer of NLRP1 inflammasome responses [1-3]. Moreover, this molecule has been shown to exert antitumor activity in vivo through the induction of cytokines and chemokines that participate in innate and adaptive immune responses [1-2]. 

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Key features:

  • Activator of the NLRP1 inflammasome (in human and mice)
  • Pyroptosis inducer
  • Non-selective inhibitor of serine dipeptidyl peptidases
  • Each lot is functionally tested and highly pure (≥95%)

 

Read our review Read our review on NLRP1 & NLRP3 inflammasome sensors

 

References:

1. Okondo MC et al., 2017. DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat Chem Biol. 2017;13(1):46-53.
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 (15): 5471–5480.
3. Hollingsworth LR et al., 2021. DPP9 sequesters the C terminus of NLRP1 to repress inflammasome activation. Nature. 2021;592(7856):778-783.

 

All products are for research use only, and not for human or veterinary use.

SPECIFICATIONS

Specifications

CAS number
150080-09-4
Chemical formula

C9H19BN2O3.CH3SO3H

Molecular weight
310.18 g/mol
Working concentration

10 - 100 µM for cell culture assays

Solubility

40 mg/ml in H2O

Tested applications

cellular assays

Quality control

Biological activity confirmed using cellular assays, absence of bacterial contamination confirmed using HEK-Blue™ TLR2 and HEK-Blue™ TLR4 cells

CONTENTS

Contents

  • Product: 
    Val-boroPro
  • Cat code: 
    tlrl-vbp-10
  • Quantity: 
    10 mg

Shipping & Storage

  • Shipping method:  Room temperature
  • Storage:

    • -20°C

    Caution:

    • Avoid repeated freeze-thaw cycles

Details

VbP (also known as Talabostat, PT-100 or L-valinyl-L-boroproline) is a non-selective DPP inhibitor able to activate both the CARD8 (caspase recruitment domain-containing protein 8) and the NLRP1 inflammasomes [1]. It weakens the inhibitory complex between DPP9 active site and the bioactive C-terminus of NLRP1 by direct competition for DPP9’s catalytic residues. As a result,  the single bound C-terminal NLRP1 is released. At the same time, the full length NLRP1 is displaced from the interaction, which leads to auto-proteolysis of its FIIND domain and to proteasomal degradation of the N-terminal domain  [3]. The bioactive C-terminal CARD domain is released, activates Caspase-1 via oligomerization with ASC proteins, and subsequently, triggers pyroptosis [2-4].

Additionally, VbP exhibits potent antitumor activity in vivo through the induction of cytokines and chemokines activating the innate and adaptive immune system [2,4]. It also increases the effect of antitumor antibodies like Rituximab and Trastuzumab in xenograft models of human CD20+ B cell lymphoma and HER2+ colon carcinoma, respectively [4].

 

1. Sato T, et al., 2019Hatano R, Iwao N, Ohnuma K, Morimoto C. DPP8 is a novel therapeutic target for multiple myeloma. Sci Rep.  2;9(1):18094.
2. Okondo MC, et al., 2017. DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat Chem Biol. 13(1):46-53.  
3. Hollingsworth LR, et al., 2021. DPP9 sequesters the C terminus of NLRP1 to repress inflammasome activation. Nature. 592(7856):778-783. 
4. 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 (15): 5471–5480. 

 

Chemical structure of Val-boroPro:

Chemical structure of Val-boroPro

DOCUMENTS

Documents

Val-boroPro

Technical Data Sheet

Safety Data Sheet

Validation Data Sheet

Certificate of analysis

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