Talabostat

inhibitors of the serine peptidases DPP8 and DPP9 (DPP8/9) induce pro-caspase-1-dependent pyroptosis in monocytes and macrophages. inhibition of DPP8 and/or DPP9 has been shown to cause severe toxicity in preclinical species

General

Type : Peptide, Pyrrolidine, Boron compound

Chemical_Nomenclature : [(2R)-1-[(2S)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid

Canonical SMILES : B(C1CCCN1C(=O)C(C(C)C)N)(O)O

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

InChIKey : FKCMADOPPWWGNZ-YUMQZZPRSA-N

Other name(s) : Val-boro-pro  ||  Val-boroPro  ||  ValboroPro  ||  UNII-KZ1O2SH88Z  ||  Talabostat(PT100)  ||  VbP  ||  PT-100  ||  DB06182


MW : 214.07

Formula : C9H19BN2O3

CAS_number : 149682-77-9

PubChem : 6918572

UniChem : FKCMADOPPWWGNZ-YUMQZZPRSA-N

Target

Families : Talabostat ligand of proteins in family
DPP4N_Peptidase_S9

Structure :
6X6C 6HP8

Protein :
human-DPP8 human-DPP9 human-FAP

References (18)

Title : DPP9 sequesters the C terminus of NLRP1 to repress inflammasome activation - Hollingsworth_2021_Nature_592_778
Author(s) : Hollingsworth LR , Sharif H , Griswold AR , Fontana P , Mintseris J , Dagbay KB , Paulo JA , Gygi SP , Bachovchin DA , Wu H
Ref : Nature , 592 :778 , 2021
Abstract :
PubMedSearch : Hollingsworth_2021_Nature_592_778
PubMedID: 33731932
Gene_locus related to this paper: human-DPP9

Title : Dipeptidyl peptidase 9 sets a threshold for CARD8 inflammasome formation by sequestering its active C-terminal fragment - Sharif_2021_Immunity__
Author(s) : Sharif H , Hollingsworth LR , Griswold AR , Hsiao JC , Wang Q , Bachovchin DA , Wu H
Ref : Immunity , : , 2021
Abstract :
PubMedSearch : Sharif_2021_Immunity__
PubMedID: 34019797
Gene_locus related to this paper: human-DPP9

Title : Structural mechanism of CARD8 regulation by DPP9 - Sharif_2021_Biorxiv__
Author(s) : Sharif H , Hollingsworth LR , Griswold AR , Hsiao JC , Wang QH , Bachovchin DA , Wu H
Ref : Biorxiv , : , 2021
Abstract :
PubMedSearch : Sharif_2021_Biorxiv__
PubMedID:
Gene_locus related to this paper: human-DPP9

Title : Activation of the CARD8 Inflammasome Requires a Disordered Region - Chui_2020_Cell.Rep_33_108264
Author(s) : Chui AJ , Griswold AR , Taabazuing CY , Orth EL , Gai K , Rao SD , Ball DP , Hsiao JC , Bachovchin DA
Ref : Cell Rep , 33 :108264 , 2020
Abstract :
PubMedSearch : Chui_2020_Cell.Rep_33_108264
PubMedID: 33053349
Gene_locus related to this paper: human-DPP8 , human-DPP9

Title : DPP9 directly sequesters the NLRP1 C-terminus to repress inflammasome activation - Hollingsworth_2020_Biorxiv__
Author(s) : Hollingsworth LR , Sharif H , Griswold AR , Fontana P , Mintseris J , Dagbay KB , Paulo JA , Gygi SP , Bachovchin DA , Wu
Ref : Biorxiv , : , 2020
Abstract :
PubMedSearch : Hollingsworth_2020_Biorxiv__
PubMedID:
Gene_locus related to this paper: human-DPP9

Title : The NLRP1 and CARD8 inflammasomes - Taabazuing_2020_Immunol.Rev_297_13
Author(s) : Taabazuing CY , Griswold AR , Bachovchin DA
Ref : Immunol Rev , 297 :13 , 2020
Abstract :
PubMedSearch : Taabazuing_2020_Immunol.Rev_297_13
PubMedID: 32558991
Gene_locus related to this paper: human-DPP9

Title : DPP9's Enzymatic Activity and Not Its Binding to CARD8 Inhibits Inflammasome Activation - Griswold_2019_ACS.Chem.Biol_14_2424
Author(s) : Griswold AR , Ball DP , Bhattacharjee A , Chui AJ , Rao SD , Taabazuing CY , Bachovchin DA
Ref : ACS Chemical Biology , 14 :2424 , 2019
Abstract :
PubMedSearch : Griswold_2019_ACS.Chem.Biol_14_2424
PubMedID: 31525884
Gene_locus related to this paper: human-DPP9

Title : Inhibition of Dpp8\/9 Activates the Nlrp1b Inflammasome - Okondo_2018_Cell.Chem.Biol_25_262
Author(s) : Okondo MC , Rao SD , Taabazuing CY , Chui AJ , Poplawski SE , Johnson DC , Bachovchin DA
Ref : Cell Chemical Biology , 25 :262 , 2018
Abstract :
PubMedSearch : Okondo_2018_Cell.Chem.Biol_25_262
PubMedID: 29396289
Gene_locus related to this paper: human-DPP8 , human-DPP9

Title : Human DPP9 represses NLRP1 inflammasome and protects against autoinflammatory diseases via both peptidase activity and FIIND domain binding - Zhong_2018_J.Biol.Chem_293_18864
Author(s) : Zhong FL , Robinson K , Teo DET , Tan KY , Lim C , Harapas CR , Yu CH , Xie WH , Sobota RM , Au VB , Hopkins R , D'Osualdo A , Reed JC , Connolly JE , Masters SL , Reversade B
Ref : Journal of Biological Chemistry , 293 :18864 , 2018
Abstract :
PubMedSearch : Zhong_2018_J.Biol.Chem_293_18864
PubMedID: 30291141
Gene_locus related to this paper: human-DPP9

Title : Pyroptosis and Apoptosis Pathways Engage in Bidirectional Crosstalk in Monocytes and Macrophages - Taabazuing_2017_Cell.Chem.Biol_24_507
Author(s) : Taabazuing CY , Okondo MC , Bachovchin DA
Ref : Cell Chemical Biology , 24 :507 , 2017
Abstract :
PubMedSearch : Taabazuing_2017_Cell.Chem.Biol_24_507
PubMedID: 28392147
Gene_locus related to this paper: human-DPP8 , human-DPP9

Title : DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis - Okondo_2017_Nat.Chem.Biol_13_46
Author(s) : Okondo MC , Johnson DC , Sridharan R , Go EB , Chui AJ , Wang MS , Poplawski SE , Wu W , Liu Y , Lai JH , Sanford DG , Arciprete MO , Golub TR , Bachovchin WW , Bachovchin DA
Ref : Nat Chemical Biology , 13 :46 , 2017
Abstract :
PubMedSearch : Okondo_2017_Nat.Chem.Biol_13_46
PubMedID: 27820798
Gene_locus related to this paper: human-DPP8 , human-DPP9

Title : Val-boroPro accelerates T cell priming via modulation of dendritic cell trafficking resulting in complete regression of established murine tumors - Walsh_2013_PLoS.One_8_e58860
Author(s) : Walsh MP , Duncan B , Larabee S , Krauss A , Davis JP , Cui Y , Kim SY , Guimond M , Bachovchin W , Fry TJ
Ref : PLoS ONE , 8 :e58860 , 2013
Abstract :
PubMedSearch : Walsh_2013_PLoS.One_8_e58860
PubMedID: 23554941

Title : 4-Substituted boro-proline dipeptides: synthesis, characterization, and dipeptidyl peptidase IV, 8, and 9 activities - Wu_2012_Bioorg.Med.Chem.Lett_22_5536
Author(s) : Wu W , Liu Y , Milo LJ, Jr. , Shu Y , Zhao P , Li Y , Woznica I , Yu G , Sanford DG , Zhou Y , Poplawski SE , Connolly BA , Sudmeier JL , Bachovchin WW , Lai JH
Ref : Bioorganic & Medicinal Chemistry Lett , 22 :5536 , 2012
Abstract :
PubMedSearch : Wu_2012_Bioorg.Med.Chem.Lett_22_5536
PubMedID: 22853995

Title : Pro-soft Val-boroPro: a strategy for enhancing in vivo performance of boronic acid inhibitors of serine proteases - Poplawski_2011_J.Med.Chem_54_2022
Author(s) : Poplawski SE , Lai JH , Sanford DG , Sudmeier JL , Wu W , Bachovchin WW
Ref : Journal of Medicinal Chemistry , 54 :2022 , 2011
Abstract :
PubMedSearch : Poplawski_2011_J.Med.Chem_54_2022
PubMedID: 21388136

Title : Phase II trial of talabostat and docetaxel in advanced non-small cell lung cancer - Eager_2009_Clin.Oncol.(R.Coll.Radiol)_21_464
Author(s) : Eager RM , Cunningham CC , Senzer N , Richards DA , Raju RN , Jones B , Uprichard M , Nemunaitis J
Ref : Clin Oncol (R Coll Radiol) , 21 :464 , 2009
Abstract :
PubMedSearch : Eager_2009_Clin.Oncol.(R.Coll.Radiol)_21_464
PubMedID: 19501491

Title : Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potency and in vivo efficacy and safety - Connolly_2008_J.Med.Chem_51_6005
Author(s) : Connolly BA , Sanford DG , Chiluwal AK , Healey SE , Peters DE , Dimare MT , Wu W , Liu Y , Maw H , Zhou Y , Li Y , Jin Z , Sudmeier JL , Lai JH , Bachovchin WW
Ref : Journal of Medicinal Chemistry , 51 :6005 , 2008
Abstract :
PubMedSearch : Connolly_2008_J.Med.Chem_51_6005
PubMedID: 18783201

Title : Phase II trial of single agent Val-boroPro (Talabostat) inhibiting Fibroblast Activation Protein in patients with metastatic colorectal cancer - Narra_2007_Cancer.Biol.Ther_6_1691
Author(s) : Narra K , Mullins SR , Lee HO , Strzemkowski-Brun B , Magalong K , Christiansen VJ , McKee PA , Egleston B , Cohen SJ , Weiner LM , Meropol NJ , Cheng JD
Ref : Cancer Biol Ther , 6 :1691 , 2007
Abstract :
PubMedSearch : Narra_2007_Cancer.Biol.Ther_6_1691
PubMedID: 18032930

Title : Effect of deoxycoformycin and Val-boroPro on the associated catalytic activities of lymphocyte CD26 and ecto-adenosine deaminase - Jeanfavre_1996_Biochem.Pharmacol_52_1757
Author(s) : Jeanfavre DD , Woska JR, Jr. , Pargellis CA , Kennedy CA , Prendergast J , Stearns C , Reilly PL , Barton RW , Bormann BJ
Ref : Biochemical Pharmacology , 52 :1757 , 1996
Abstract :
PubMedSearch : Jeanfavre_1996_Biochem.Pharmacol_52_1757
PubMedID: 8986139