Inhibitor Report for: ABT-279
General
Type Pyrrolidine , Cyanide Chemical_Nomenclature 2-[4-[[2-[(2S,5R)-2-[amino(hydroxy)methyl]-5-ethynylpyrrolidin-1-yl]-2-oxoethyl]amino]-4-methylpiperidin-1-yl]pyridine-4-carboxylic acid Canonical SMILES CC1(CCN(CC1)C2=NC=CC(=C2)C(=O)O)NCC(=O)N3C(CCC3C(N)O)C#C InChI InChI=1S/C21H29N5O4/c1-3-15-4-5-16(19(22)28)26(15)18(27)13-24-21(2)7-10-25(11-8-21)17-12-14(20(29)30)6-9-23-17/h1,6,9,12,15-16,19,24,28H,4-5,7-8,10-11,13,22H2,2H3,(H,29,30)/t15-,16-,19?/m0/s1 InChIKey XIDTWITXVPICLF-NRAVZPKASA-N Other name(s) AXD ; 2-[4-({2-[(2s,5r)-2-(Aminomethyl)-5-Ethynylpyrrolidin-1-Yl]-2-Oxoethyl}amino)-4-Methylpiperidin-1-Yl]isonicotinic Acid
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Target
Families | ABT-279 ligand of proteins in family: DPP4N_Peptidase_S9 Stucture | 1 structure : 2I03 : Crystal structure of human dipeptidyl peptidase 4 (DPP-IV) with potent alkynyl cyanopyrrolidine (ABT-279) Protein | human-DPP4
References:
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ABT-279
Title: Discovery of 2-[4-{{2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]- 4-methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279): a very potent, selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-IV, useful for the treatment of diabetes
Madar DJ , Kopecka H , Pireh D , Yong H , Pei Z , Li X , Wiedeman PE , Djuric SW , von Geldern TW and Trevillyan JM <21 more author(s)>
Madar DJ , Kopecka H , Pireh D , Yong H , Pei Z , Li X , Wiedeman PE , Djuric SW , von Geldern TW , Fickes MG , Bhagavatula L , McDermott T , Wittenberger S , Richards SJ , Longenecker KL , Stewart KD , Lubben TH , Ballaron SJ , Stashko MA , Long MA , Wells H , Zinker BA , Mika AK , Beno DW , Kempf-Grote AJ , Polakowski J , Segreti J , Reinhart GA , Fryer RM , Sham HL , Trevillyan JM (- 21)
Ref: Journal of Medicinal Chemistry, 49 :6416, 2006 : PubMed Abstract ESTHER: Madar_2006_J.Med.Chem_49_6416 PubMedSearch: Madar 2006 J.Med.Chem 49 6416 PubMedID: 17034148 Gene_locus related to this paper: human-DPP4 Inhibitor(s) related to this paper: ABT-279 Abstract
Dipeptidyl peptidase-IV (DPP-IV) inhibitors are poised to be the next major drug class for the treatment of type 2 diabetes. Structure-activity studies of substitutions at the C5 position of the 2-cyanopyrrolidide warhead led to the discovery of potent inhibitors of DPP-IV that lack activity against DPP8 and DPP9. Further modification led to an extremely potent (Ki(DPP)(-)(IV) = 1.0 nM) and selective (Ki(DPP8) > 30 microM; Ki(DPP9) > 30 microM) clinical candidate, ABT-279, that is orally available, efficacious, and remarkably safe in preclinical safety studies.