talabostat   Click here for help

GtoPdb Ligand ID: 9892

Synonyms: compound 1 [PMID: 18783201] | PT-100 | PT100 | Val-boro-pro | Val-boroPro
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Talabostat (PT-100, or Val-boroPro) is a compound with potent anti-tumour activity. It is a non-selective inhibitor of post-proline-cleaving serine proteases (DPP enzymes). Talabostat activates macrophages at least in part via inhibition of the serine peptidase, fibroblast activation protein (FAP), an action that has been examined for anti-cancer utility [2,4-5] and anti-fibrotic potential [3]. More recently talabostat has been reported as an inhibitor of the cytosolic serine dipeptidyl peptidases DPP8 and DPP9, and that inhibition of these related enzymes stimulates the immune system via the selective promotion of proinflammatory cell death (pyroptosis) of monocytes and macrophages [6]. This process involves DPP8/9-induced activation of the NOD-like pattern recognition receptor NLRP1, a protein that acts as an inflammasome sensor, followed by activation of pro-caspase-1 and eventually to pyroptosis [7].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 3
Rotatable bonds 4
Topological polar surface area 86.79
Molecular weight 214.15
XLogP -0.57
No. Lipinski's rules broken 0
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Isomeric SMILES CC([C@@H](C(=O)N1CCC[C@H]1B(O)O)N)C
InChI 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
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Summary of Clinical Use Click here for help
Talabostat has completed Phase 2 clinical trials for cancer indications (e.g. advanced melanoma [2], and metastatic colorectal cancer [5]) but both of these trials showed minimal clinical activity in the selected patients groups. Two Phase 3 trials in NSCLC (NCT00243204 and NCT00290017) were put on hold at the behest of the FDA, and the studies were terminated.