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PDBsum entry 2onc
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Contents |
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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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Crystal structure of human dpp-4
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Structure:
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Dipeptidyl peptidase 4. Chain: a, b, c, d. Synonym: dipeptidyl peptidase, dpp iv, t-cell activation antigen cd26, tp103, adenosine deaminase complexing protein 2, adabp. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: dpp4, adcp2, cd26. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
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Resolution:
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2.55Å
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R-factor:
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0.198
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R-free:
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0.254
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Authors:
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J.Feng,Z.Zhang,M.B.Wallace,J.A.Stafford,S.W.Kaldor,D.B.Kassel, M.Navre,L.Shi,R.J.Skene,T.Asakawa,K.Takeuchi,R.Xu,D.R.Webb, S.L.Gwaltney
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Key ref:
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J.Feng
et al.
(2007).
Discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV.
J Med Chem,
50,
2297-2300.
PubMed id:
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Date:
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23-Jan-07
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Release date:
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04-Mar-08
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PROCHECK
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Headers
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References
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P27487
(DPP4_HUMAN) -
Dipeptidyl peptidase 4 from Homo sapiens
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Seq:
Struc:
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766 a.a.
724 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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Enzyme class:
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E.C.3.4.14.5
- dipeptidyl-peptidase Iv.
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Reaction:
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Release of an N-terminal dipeptide, Xaa-Xbb-|-Xcc, from a polypeptide, preferentially when Xbb is Pro, provided Xcc is neither Pro nor hydroxyproline.
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J Med Chem
50:2297-2300
(2007)
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PubMed id:
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Discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV.
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J.Feng,
Z.Zhang,
M.B.Wallace,
J.A.Stafford,
S.W.Kaldor,
D.B.Kassel,
M.Navre,
L.Shi,
R.J.Skene,
T.Asakawa,
K.Takeuchi,
R.Xu,
D.R.Webb,
S.L.Gwaltney.
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ABSTRACT
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Alogliptin is a potent, selective inhibitor of the serine protease dipeptidyl
peptidase IV (DPP-4). Herein, we describe the structure-based design and
optimization of alogliptin and related quinazolinone-based DPP-4 inhibitors.
Following an oral dose, these noncovalent inhibitors provide sustained reduction
of plasma DPP-4 activity and a lowering of blood glucose in animal models of
diabetes. Alogliptin is currently undergoing phase III trials in patients with
type 2 diabetes.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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D.L.Cao,
F.Y.Yan,
M.Wang,
C.Y.Li,
and
L.Chen
(2012).
2-Chloro-quinazolin-4(3H)-one.
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Acta Crystallogr Sect E Struct Rep Online,
68,
o1958.
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C.F.Deacon
(2011).
Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review.
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Diabetes Obes Metab,
13,
7.
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K.Motoshima,
K.Sugita,
Y.Hashimoto,
and
M.Ishikawa
(2011).
Non-competitive and selective dipeptidyl peptidase IV inhibitors with phenethylphenylphthalimide skeleton derived from thalidomide-related α-glucosidase inhibitors and liver X receptor antagonists.
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Bioorg Med Chem Lett,
21,
3041-3045.
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X.Zhang,
Z.Wang,
Y.Huang,
and
J.Wang
(2011).
Effects of chronic administration of alogliptin on the development of diabetes and β-cell function in high fat diet/streptozotocin diabetic mice.
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Diabetes Obes Metab,
13,
337-347.
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Z.H.Israili
(2011).
Advances in the treatment of type 2 diabetes mellitus.
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Am J Ther,
18,
117-152.
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C.Triplitt,
E.Cersosimo,
and
R.A.DeFronzo
(2010).
Pioglitazone and alogliptin combination therapy in type 2 diabetes: a pathophysiologically sound treatment.
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Vasc Health Risk Manag,
6,
671-690.
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H.Zettl,
M.Schubert-Zsilavecz,
and
D.Steinhilber
(2010).
Medicinal Chemistry of Incretin Mimetics and DPP-4 Inhibitors.
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ChemMedChem,
5,
179-185.
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J.J.Neumiller,
L.Wood,
and
R.K.Campbell
(2010).
Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus.
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Pharmacotherapy,
30,
463-484.
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Y.Moritoh,
K.Takeuchi,
and
M.Hazama
(2010).
Combination treatment with alogliptin and voglibose increases active GLP-1 circulation, prevents the development of diabetes and preserves pancreatic beta-cells in prediabetic db/db mice.
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Diabetes Obes Metab,
12,
224-233.
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C.F.Deacon,
and
J.J.Holst
(2009).
Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes.
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Adv Ther,
26,
488-499.
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J.Jiang,
J.Qing,
and
L.Z.Gong
(2009).
Asymmetric synthesis of 3-amino-delta-lactams and benzo[a]quinolizidines by catalytic cyclization reactions involving azlactones.
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Chemistry,
15,
7031-7034.
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J.Rosenstock,
M.S.Rendell,
J.L.Gross,
P.R.Fleck,
C.A.Wilson,
and
Q.Mekki
(2009).
Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA(1C) without causing weight gain or increased hypoglycaemia.
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Diabetes Obes Metab,
11,
1145-1152.
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M.A.Nauck,
G.C.Ellis,
P.R.Fleck,
C.A.Wilson,
and
Q.Mekki
(2009).
Efficacy and safety of adding the dipeptidyl peptidase-4 inhibitor alogliptin to metformin therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a multicentre, randomised, double-blind, placebo-controlled study.
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Int J Clin Pract,
63,
46-55.
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R.E.Pratley,
J.E.Reusch,
P.R.Fleck,
C.A.Wilson,
Q.Mekki,
P.Castano,
J.Cuadrado,
L.Maffei,
G.Sposetti,
M.Ulla,
C.Allan,
M.dEmden,
D.Oneal,
A.Roberts,
C.Chrisman,
J.Gross,
C.Hayashida,
R.Rea,
K.Derwahl,
J.Hensen,
G.Klausmann,
S.Laus,
R.Lehmann,
V.von Behren,
A.Granandos-Fuentes,
E.Turcios-Juarez,
L.Koranyi,
K.Nagy,
G.Bantwal,
S.Chowdhury,
K.Prasanna Kumar,
N.Thomas,
M.Viswanathan,
R.van Leendert,
A.Dissanayake,
R.Scott,
S.Young,
L.Gonzales,
G.Molina,
L.More,
G.Ellis,
M.Seeber,
L.De Teresa,
J.Moreiro,
J.Barrera,
A.Behnke,
G.Bonabi,
R.Broker,
A.Caos,
C.Chappel,
W.Cheatham,
L.Cohen,
C.Corder,
W.Curtis,
P.Davis,
L.Dunn,
J.Earl,
S.Elliott,
J.Fidelholtz,
N.Fishman,
D.Fitz-Patrick,
L.Fogelfeld,
S.Glenn,
A.Guevara,
M.Hassman,
C.Herring,
D.Hurley,
C.Jones,
J.Kang,
E.Kerwin,
M.Kipnes,
W.Koppel,
J.Krasner,
S.Landgarten,
S.Lerman,
D.Levenson,
J.Liljenquist,
M.Lindley,
R.Lipetz,
T.Littlejohn,
W.Long,
C.Lowder,
J.Lucas,
L.Lynn,
G.Mark,
R.Marple,
S.Mayeda,
D.Morin,
J.Mullen,
P.Norwood,
S.Oates,
A.Odugbesan,
F.Phillips,
S.Plevin,
L.Popeil,
R.Pratley,
K.Pudi,
G.Raad,
J.Reed,
and
M.Rendell
(2009).
Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin added to pioglitazone in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study.
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Curr Med Res Opin,
25,
2361-2371.
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R.E.Pratley,
M.S.Kipnes,
P.R.Fleck,
C.Wilson,
Q.Mekki,
P.Castano,
J.Cuadrado,
L.Maffei,
F.Massari,
G.Sposetti,
M.Ulla,
S.Colagiuri,
M.dEmden,
D.O'Neal,
J.Prins,
A.Roberts,
M.Dinato,
A.Forti,
J.Gross,
C.Hayashida,
J.Neto,
R.Rea,
L.Aguirre,
G.Gonzalo,
F.Munizaga,
F.Luna-Sevez,
A.Granandos-Fuentes,
L.Ramirez-Roca,
F.Sanchez-Morales,
K.Prasanna Kumar,
N.Rais,
V.Seshiah,
N.Thomas,
M.Viswanathan,
V.Viswanathan,
C.Dueñas-Garcia,
G.Gonzalez-Galvez,
C.Gonzalez-Villalpando,
F.Mar-Arevalo,
E.Morales-Villegas,
F.Salinas-Gonzalez,
A.Dees,
A.Deijl,
A.Dissanayake,
J.Krebs,
R.Scott,
S.Young,
H.Arbañil,
S.Corigliano,
L.Gonzales,
A.Luna,
G.Molina,
L.More,
J.Kuleta,
J.Loba,
P.Mader,
A.Mikolajczyk-Swatko,
J.Sawer-Szewczyk,
A.Stankiewicz,
A.Stepien,
W.Boyd,
L.Burgess,
G.Ellis,
P.Joshi,
L.De Teresa,
T.Hall,
C.McKinnon,
J.Ryan,
J.Barrera,
G.Bonabi,
C.Chappel,
W.Cheatham,
L.Cohen,
C.Corder,
S.Elliott,
D.Fitz-Patrick,
M.Hassman,
P.Hollander,
D.Hurley,
C.Jones,
M.Kipnes,
W.Koppel,
S.Landgarten,
A.Lewin,
M.Lindley,
R.Lipetz,
T.Littlejohn,
J.Lucas,
G.Mark,
R.Marple,
E.Mattson,
S.Mayeda,
M.McAdoo,
D.Morin,
J.Mullen,
J.Neutel,
P.Norwood,
S.Oates,
A.Odugbesan,
and
F.Phillips
(2009).
Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy.
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Diabetes Obes Metab,
11,
167-176.
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Y.Moritoh,
K.Takeuchi,
T.Asakawa,
O.Kataoka,
and
H.Odaka
(2009).
Combining a dipeptidyl peptidase-4 inhibitor, alogliptin, with pioglitazone improves glycaemic control, lipid profiles and beta-cell function in db/db mice.
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Br J Pharmacol,
157,
415-426.
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R.A.DeFronzo,
P.R.Fleck,
C.A.Wilson,
and
Q.Mekki
(2008).
Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes and inadequate glycemic control: a randomized, double-blind, placebo-controlled study.
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Diabetes Care,
31,
2315-2317.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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Links
