Talabostat . mesylate
| Code | Size | Price |
|---|
| AG-CR1-3541-M010 | 10 mg | £70.00 |
Quantity:
| AG-CR1-3541-M050 | 50 mg | £210.00 |
Quantity:
Prices exclude any Taxes / VAT
Overview
Regulatory Status: RUO
Shipping:
AMBIENT
Storage:
Short Term: +4°C, Long Term: -20°C
Documents
Further Information
Alternate Names/Synonyms:
Valinyl-L-boroproline; Val-boro-Pro; BXCL 701; PT-100; B-[(2R)-1-[(2S)-2-Amino-3-methyl-1-oxobutyl]-2-pyrrolidinyl]boronic acid methanesulfonate
Appearance:
White to off-white solid.
CAS:
150080-09-4
EClass:
32160000
Form (Short):
liquid
Handling Advice:
Keep cool and dry.
InChi:
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)/p-1/t7-,8-;/m0./s1
InChiKey:
OXYYOEIGQRXGPI-WSZWBAFRSA-M
Long Description:
Chemical. CAS: 150080-09-4. Formula: C9H19BN2O3 . CH4O3S. MW: 310.2. Talabostat is an orally bioavailable non-selective inhibitor of dipeptidyl-peptidases (DPPs), including DPP-4, DPP-7/QPP, DPP-8, DPP-9, fibroblast activation protein (FAP) and prolyl endopeptidase (PREP; PEP) (IC50s = >4, 310, 4, 11, 560 and 390 nM, respectively). Talabostat induces powerful anti-tumor immune responses in cancer models. Talabostat is a NLRP1 and caspase recruitment domain family member 8 (CARD8) inflammasome activator. Talabostat triggers an immunostimulatory form of programmed cell death known as pyroptosis selectively in monocytes and macrophages. DPP8/9 inhibition by Talabostat activates the inflammasome sensor protein Nlrp1b, which in turn activates pro-caspase-1 to mediate pyroptosis, suggesting that DPP8/9 serve as an intracellular checkpoint to restrain Nlrp1b and the innate immune system. Talabostat has anti-obesity properties and lowers body weight, blood glucose, plasma insulin and total cholesterol while improving glucose tolerance and insulin sensitivity in mouse models. It has also been shown to elevate FGF21 levels in plasma.
MDL:
MFCD13194906
Molecular Formula:
C9H19BN2O3 . CH4O3S
Molecular Weight:
310.2
Other data:
For NLRP1 Inflammasome activation protocol, see reference H. Guo & J.P.Y. Ting; Curr. Protocols Immunol. 131, e107 (2020).
Package Type:
Vial
Product Description:
Talabostat is an orally bioavailable non-selective inhibitor of dipeptidyl-peptidases (DPPs), including DPP-4, DPP-7/QPP, DPP-8, DPP-9, fibroblast activation protein (FAP) and prolyl endopeptidase (PREP; PEP) (IC50s = >4, 310, 4, 11, 560 and 390 nM, respectively). Talabostat induces powerful anti-tumor immune responses in cancer models. Talabostat is a NLRP1 and caspase recruitment domain family member 8 (CARD8) inflammasome activator. Talabostat triggers an immunostimulatory form of programmed cell death known as pyroptosis selectively in monocytes and macrophages. DPP8/9 inhibition by Talabostat activates the inflammasome sensor protein Nlrp1b, which in turn activates pro-caspase-1 to mediate pyroptosis, suggesting that DPP8/9 serve as an intracellular checkpoint to restrain Nlrp1b and the innate immune system. Talabostat has anti-obesity properties and lowers body weight, blood glucose, plasma insulin and total cholesterol while improving glucose tolerance and insulin sensitivity in mouse models. It has also been shown to elevate FGF21 levels in plasma.
Purity:
>98% (HPLC)
SMILES:
CC(C)[C@H](N)C(N1CCC[C@H]1B(O)O)=O.CS(=O)([O-])=O
Solubility Chemicals:
Soluble in DMSO (25mg/ml) or water (25mg/ml).
Transportation:
Non-hazardous
UNSPSC Category:
Biochemical Reagents
UNSPSC Number:
12352200
Use & Stability:
Stable for at least 2 years after receipt when stored at -20°C.
References
PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism: S. Adams, et al.; Cancer Res. 64, 5471 (2004) | Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: Potential importance of selectivity over dipeptidyl peptidases 8 and 9: G.R. Lankas, et al.; Diabetes 54, 2988 (2005) | Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potency and in vivo efficacy and safety: B.A. Connolly, et al.; J. Med. Chem. 51, 6005 (2008) | Val-BoroPro Accelerates T Cell Priming via Modulation of Dendritic Cell Trafficking Resulting in Complete Regression of Established Murine Tumors: M.P. Walsh, et al.; PLoS One 8, e58860 (2013) | Fibroblast activation protein (FAP) as a novel metabolic target: M.A. Sanchez-Garrido, et al.; Mol. Metab. 5, 1015 (2016) | DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis: M.C. Okondo, et al.; Nat. Chem. Biol. 13, 46 (2017) | Inhibition of Dpp8/9 activates the Nlrp1b inflammasome: M.C. Okondo, et al.; Cell Chem. Biol. 25, 262 (2018) | DPP8/DPP9 inhibitor-induced pyroptosis for treatment of acute myeloid leukemia: D.C. Johnson, et al.; Nat. Med. 24, 1151 (2018) | Human DPP9 represses NLRP1 inflammasome and protects against autoinflammatory diseases via both peptidase activity and FIIND domain binding: F.L. Zhong, et al.; J. Biol. Chem. 293, 18864 (2018) | Enteroviral 3C protease activates the human NLRP1 inflammasome in airway epithelia: K.S. Robinson, et al.; Science 370, 1182 (2020) | DPP8/9 inhibitors activate the CARD8 inflammasome in resting lymphocytes: D.C. Johnson, et al.; Cell Death Dis. 11, 628 (2020) | The NLRP1 Inflammasome in Human Skin and Beyond: G. Fenini, et al.; Int. J. Mol. Sci. 21, 4788 (2020) (Review) | Inflammasome Assays In Vitro and in Mouse Models: H. Guo & J.P.Y. Ting; Curr. Protocols Immunol. 131, e107 (2020) [Protocol] | Talabostat Alleviates Obesity and Associated Metabolic Dysfunction via Suppression of Macrophage-Driven Adipose Inflammation: Y. Wu, et al.; Obesity 29, 327 (2021) | Virus-mediated inactivation of anti-apoptotic Bcl-2 family members promotes Gasdermin-E-dependent pyroptosis in barrier epithelial cells: M.H. Orzalli, et al.; Immunity 54, P1447 (2021)