Ignet

Gene Information

Gene symbol: DPP8

Gene name: dipeptidyl-peptidase 8

HGNC ID: 16490

Synonyms: DP8, DPRP1, MSTP141, FLJ14920, FLJ20283, MGC26191

Related Genes

#	Gene Symbol	Number of hits
1	ANPEP	1 hits
2	DPP10	1 hits
3	DPP4	1 hits
4	DPP7	1 hits
5	DPP9	1 hits
6	DSPP	1 hits
7	F2	1 hits
8	FAP	1 hits
9	IL6	1 hits
10	INS	1 hits
11	NPY	1 hits
12	PEPD	1 hits
13	PRCP	1 hits
14	PREP	1 hits
15	PYY	1 hits
16	XPNPEP2	1 hits

Related Sentences

#	PMID	Sentence
1	11012666	Here we describe DPP8, a novel human postproline dipeptidyl aminopeptidase that is homologous to DPPIV and FAP.
2	11012666	Northern-blot hybridization showed that the tissue expression of DPP8 mRNA is ubiquitous, similar to that of DPPIV.
3	11012666	The DPP8 gene was localized to chromosome 15q22, distinct from a closely related gene at 19p13.3 which we named DPP9.
4	11012666	The full-length DPP8 cDNA codes for an 882-amino-acid protein that has about 27% identity and 51% similarity to DPPIV and FAP, but no transmembrane domain and no N-linked or O-linked glycosylation.
5	11012666	Purified recombinant DPP8 hydrolyzed the DPPIV substrates Ala-Pro, Arg-Pro and Gly-Pro.
6	11012666	Thus recombinant DPP8 shares a postproline dipeptidyl aminopeptidase activity with DPPIV and FAP.
7	11012666	The similarities between DPP8 and DPPIV in tissue expression pattern and substrates suggests a potential role for DPP8 in T-cell activation and immune function.
8	11012666	Here we describe DPP8, a novel human postproline dipeptidyl aminopeptidase that is homologous to DPPIV and FAP.
9	11012666	Northern-blot hybridization showed that the tissue expression of DPP8 mRNA is ubiquitous, similar to that of DPPIV.
10	11012666	The DPP8 gene was localized to chromosome 15q22, distinct from a closely related gene at 19p13.3 which we named DPP9.
11	11012666	The full-length DPP8 cDNA codes for an 882-amino-acid protein that has about 27% identity and 51% similarity to DPPIV and FAP, but no transmembrane domain and no N-linked or O-linked glycosylation.
12	11012666	Purified recombinant DPP8 hydrolyzed the DPPIV substrates Ala-Pro, Arg-Pro and Gly-Pro.
13	11012666	Thus recombinant DPP8 shares a postproline dipeptidyl aminopeptidase activity with DPPIV and FAP.
14	11012666	The similarities between DPP8 and DPPIV in tissue expression pattern and substrates suggests a potential role for DPP8 in T-cell activation and immune function.
15	11012666	Here we describe DPP8, a novel human postproline dipeptidyl aminopeptidase that is homologous to DPPIV and FAP.
16	11012666	Northern-blot hybridization showed that the tissue expression of DPP8 mRNA is ubiquitous, similar to that of DPPIV.
17	11012666	The DPP8 gene was localized to chromosome 15q22, distinct from a closely related gene at 19p13.3 which we named DPP9.
18	11012666	The full-length DPP8 cDNA codes for an 882-amino-acid protein that has about 27% identity and 51% similarity to DPPIV and FAP, but no transmembrane domain and no N-linked or O-linked glycosylation.
19	11012666	Purified recombinant DPP8 hydrolyzed the DPPIV substrates Ala-Pro, Arg-Pro and Gly-Pro.
20	11012666	Thus recombinant DPP8 shares a postproline dipeptidyl aminopeptidase activity with DPPIV and FAP.
21	11012666	The similarities between DPP8 and DPPIV in tissue expression pattern and substrates suggests a potential role for DPP8 in T-cell activation and immune function.
22	11012666	Here we describe DPP8, a novel human postproline dipeptidyl aminopeptidase that is homologous to DPPIV and FAP.
23	11012666	Northern-blot hybridization showed that the tissue expression of DPP8 mRNA is ubiquitous, similar to that of DPPIV.
24	11012666	The DPP8 gene was localized to chromosome 15q22, distinct from a closely related gene at 19p13.3 which we named DPP9.
25	11012666	The full-length DPP8 cDNA codes for an 882-amino-acid protein that has about 27% identity and 51% similarity to DPPIV and FAP, but no transmembrane domain and no N-linked or O-linked glycosylation.
26	11012666	Purified recombinant DPP8 hydrolyzed the DPPIV substrates Ala-Pro, Arg-Pro and Gly-Pro.
27	11012666	Thus recombinant DPP8 shares a postproline dipeptidyl aminopeptidase activity with DPPIV and FAP.
28	11012666	The similarities between DPP8 and DPPIV in tissue expression pattern and substrates suggests a potential role for DPP8 in T-cell activation and immune function.
29	11012666	Here we describe DPP8, a novel human postproline dipeptidyl aminopeptidase that is homologous to DPPIV and FAP.
30	11012666	Northern-blot hybridization showed that the tissue expression of DPP8 mRNA is ubiquitous, similar to that of DPPIV.
31	11012666	The DPP8 gene was localized to chromosome 15q22, distinct from a closely related gene at 19p13.3 which we named DPP9.
32	11012666	The full-length DPP8 cDNA codes for an 882-amino-acid protein that has about 27% identity and 51% similarity to DPPIV and FAP, but no transmembrane domain and no N-linked or O-linked glycosylation.
33	11012666	Purified recombinant DPP8 hydrolyzed the DPPIV substrates Ala-Pro, Arg-Pro and Gly-Pro.
34	11012666	Thus recombinant DPP8 shares a postproline dipeptidyl aminopeptidase activity with DPPIV and FAP.
35	11012666	The similarities between DPP8 and DPPIV in tissue expression pattern and substrates suggests a potential role for DPP8 in T-cell activation and immune function.
36	11012666	Here we describe DPP8, a novel human postproline dipeptidyl aminopeptidase that is homologous to DPPIV and FAP.
37	11012666	Northern-blot hybridization showed that the tissue expression of DPP8 mRNA is ubiquitous, similar to that of DPPIV.
38	11012666	The DPP8 gene was localized to chromosome 15q22, distinct from a closely related gene at 19p13.3 which we named DPP9.
39	11012666	The full-length DPP8 cDNA codes for an 882-amino-acid protein that has about 27% identity and 51% similarity to DPPIV and FAP, but no transmembrane domain and no N-linked or O-linked glycosylation.
40	11012666	Purified recombinant DPP8 hydrolyzed the DPPIV substrates Ala-Pro, Arg-Pro and Gly-Pro.
41	11012666	Thus recombinant DPP8 shares a postproline dipeptidyl aminopeptidase activity with DPPIV and FAP.
42	11012666	The similarities between DPP8 and DPPIV in tissue expression pattern and substrates suggests a potential role for DPP8 in T-cell activation and immune function.
43	11012666	Here we describe DPP8, a novel human postproline dipeptidyl aminopeptidase that is homologous to DPPIV and FAP.
44	11012666	Northern-blot hybridization showed that the tissue expression of DPP8 mRNA is ubiquitous, similar to that of DPPIV.
45	11012666	The DPP8 gene was localized to chromosome 15q22, distinct from a closely related gene at 19p13.3 which we named DPP9.
46	11012666	The full-length DPP8 cDNA codes for an 882-amino-acid protein that has about 27% identity and 51% similarity to DPPIV and FAP, but no transmembrane domain and no N-linked or O-linked glycosylation.
47	11012666	Purified recombinant DPP8 hydrolyzed the DPPIV substrates Ala-Pro, Arg-Pro and Gly-Pro.
48	11012666	Thus recombinant DPP8 shares a postproline dipeptidyl aminopeptidase activity with DPPIV and FAP.
49	11012666	The similarities between DPP8 and DPPIV in tissue expression pattern and substrates suggests a potential role for DPP8 in T-cell activation and immune function.
50	12534281	Dipeptidyl peptidase IV (DP-IV/CD26), fibroblast activation protein (FAP), DP-like 1 (DPL1), DP8, DP9, and DPL2 comprise the CD26 gene family.
51	12534281	DPIV substrates include the glucagonlike peptides, neuropeptide Y, and the chemokines CCL3, CCL5, CCL11, CCL22, and CXCL12.
52	12534281	We have proposed that the extracellular region of CD26 is analogous to prolyl oligopeptidase in consisting of an alpha/beta hydrolase domain contributed by both N- and C-terminal portions of the polypeptide and a seven-blade beta-propeller domain.
53	12534281	Replacing the C-terminal portion of the predicted alpha/beta hydrolase domain of CD26 (residues 501-766) with the homologous portion of DP8 or DP9 produced intact proteins.
54	12534281	Glu(259) of DP8, a residue distant from the catalytic triad yet greatly conserved in the CD26 gene family, was shown to be required for peptidase activity.
55	12534281	These data concord with our predicted CD26 structure, indicate that biosynthesis of a functional fragment of CD26 is difficult, and confirm the functional homology of DP8 with CD26.
56	12534281	Dipeptidyl peptidase IV (DP-IV/CD26), fibroblast activation protein (FAP), DP-like 1 (DPL1), DP8, DP9, and DPL2 comprise the CD26 gene family.
57	12534281	DPIV substrates include the glucagonlike peptides, neuropeptide Y, and the chemokines CCL3, CCL5, CCL11, CCL22, and CXCL12.
58	12534281	We have proposed that the extracellular region of CD26 is analogous to prolyl oligopeptidase in consisting of an alpha/beta hydrolase domain contributed by both N- and C-terminal portions of the polypeptide and a seven-blade beta-propeller domain.
59	12534281	Replacing the C-terminal portion of the predicted alpha/beta hydrolase domain of CD26 (residues 501-766) with the homologous portion of DP8 or DP9 produced intact proteins.
60	12534281	Glu(259) of DP8, a residue distant from the catalytic triad yet greatly conserved in the CD26 gene family, was shown to be required for peptidase activity.
61	12534281	These data concord with our predicted CD26 structure, indicate that biosynthesis of a functional fragment of CD26 is difficult, and confirm the functional homology of DP8 with CD26.
62	12534281	Dipeptidyl peptidase IV (DP-IV/CD26), fibroblast activation protein (FAP), DP-like 1 (DPL1), DP8, DP9, and DPL2 comprise the CD26 gene family.
63	12534281	DPIV substrates include the glucagonlike peptides, neuropeptide Y, and the chemokines CCL3, CCL5, CCL11, CCL22, and CXCL12.
64	12534281	We have proposed that the extracellular region of CD26 is analogous to prolyl oligopeptidase in consisting of an alpha/beta hydrolase domain contributed by both N- and C-terminal portions of the polypeptide and a seven-blade beta-propeller domain.
65	12534281	Replacing the C-terminal portion of the predicted alpha/beta hydrolase domain of CD26 (residues 501-766) with the homologous portion of DP8 or DP9 produced intact proteins.
66	12534281	Glu(259) of DP8, a residue distant from the catalytic triad yet greatly conserved in the CD26 gene family, was shown to be required for peptidase activity.
67	12534281	These data concord with our predicted CD26 structure, indicate that biosynthesis of a functional fragment of CD26 is difficult, and confirm the functional homology of DP8 with CD26.
68	12534281	Dipeptidyl peptidase IV (DP-IV/CD26), fibroblast activation protein (FAP), DP-like 1 (DPL1), DP8, DP9, and DPL2 comprise the CD26 gene family.
69	12534281	DPIV substrates include the glucagonlike peptides, neuropeptide Y, and the chemokines CCL3, CCL5, CCL11, CCL22, and CXCL12.
70	12534281	We have proposed that the extracellular region of CD26 is analogous to prolyl oligopeptidase in consisting of an alpha/beta hydrolase domain contributed by both N- and C-terminal portions of the polypeptide and a seven-blade beta-propeller domain.
71	12534281	Replacing the C-terminal portion of the predicted alpha/beta hydrolase domain of CD26 (residues 501-766) with the homologous portion of DP8 or DP9 produced intact proteins.
72	12534281	Glu(259) of DP8, a residue distant from the catalytic triad yet greatly conserved in the CD26 gene family, was shown to be required for peptidase activity.
73	12534281	These data concord with our predicted CD26 structure, indicate that biosynthesis of a functional fragment of CD26 is difficult, and confirm the functional homology of DP8 with CD26.
74	12941425	This class includes dipeptidyl peptidase IV (DPP IV; also termed CD26), fibroblast activation protein alpha (FAP; seprase), DPP7 (DPP II; quiescent cell proline dipeptidase), DPP8, DPP9, and prolyl carboxypeptidase (PCP; angiotensinase C).
75	12941425	More distant members include prolyl oligopeptidase (POP; post proline cleaving enzyme) and acylaminoacylpeptidase (AAP; acylpeptide hydrolase).
76	15584901	Four members of this family, DPIV, FAP (fibroblast activation protein), DP8 and DP9, have a rare substrate specificity, hydrolysis of a prolyl bond two residues from the N-terminus.
77	15584901	DPIV has a variety of peptide substrates, the best studied being GLP-1 (glucagon-like peptide-1), NPY (neuropeptide Y) and CXCL12.
78	15584901	The DPL (DP-like) glycoproteins that lack peptidase activity, DPL1 and DPL2, are brain-expressed potassium channel modulators.
79	15664838	To identify potent and selective chemical compounds against DPP8, we have synthesized a series of isoquinoline and isoindoline derivatives and have tested their inhibitory activity against DPP8, DPP-IV and DPP-II.
80	15664838	Isoindoline with a 1-(4,4'-difluor-benzhydryl)-piperazine group at the P2 site was observed to be a very potent DPP8 inhibitor, having an IC(50) value of 14nM with at least a 2500-fold selectivity over either DPP-IV or DPP-II.
81	15664838	To identify potent and selective chemical compounds against DPP8, we have synthesized a series of isoquinoline and isoindoline derivatives and have tested their inhibitory activity against DPP8, DPP-IV and DPP-II.
82	15664838	Isoindoline with a 1-(4,4'-difluor-benzhydryl)-piperazine group at the P2 site was observed to be a very potent DPP8 inhibitor, having an IC(50) value of 14nM with at least a 2500-fold selectivity over either DPP-IV or DPP-II.
83	15907807	In this paper, we report on (1) the kinetics of binding, (2) the type of inhibition, (3) the selectivity with respect to other peptidases, and (4) the inhibitory potency on the DPP IV catalyzed degradation of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and substance P.
84	15907807	It is a micromolar inhibitor for dipeptidyl-peptidase 8 and does not significantly inhibit dipeptidyl-peptidase II (EC 3.4.11.2), prolyl oligopeptidase (EC 3.4.21.26), aminopeptidase P (EC 3.4.11.9) or aminopeptidase M (EC 3.4.11.2).
85	15907807	There was no evidence for substrate specific inhibition of DPP IV by Vildagliptin or for important allosteric factors affecting the inhibition constant in presence of GIP and GLP-1.
86	16186403	DPP-IV is a member of a family of serine peptidases that includes quiescent cell proline dipeptidase (QPP), DPP8, and DPP9; DPP-IV is a key regulator of incretin hormones, but the functions of other family members are unknown.
87	16186403	To determine the importance of selective DPP-IV inhibition for the treatment of diabetes, we tested selective inhibitors of DPP-IV, DPP8/DPP9, or QPP in 2-week rat toxicity studies and in acute dog tolerability studies.
88	16186403	The QPP inhibitor produced reticulocytopenia in rats only, and no toxicities were noted in either species for the selective DPP-IV inhibitor.
89	16186403	The DPP8/9 inhibitor was also shown to attenuate T-cell activation in human in vitro models; a selective DPP-IV inhibitor was inactive in these assays.
90	16186403	Moreover, we found DPP-IV inhibitors that were previously reported to be active in models of immune function to be more potent inhibitors of DPP8/9.
91	16186403	DPP-IV is a member of a family of serine peptidases that includes quiescent cell proline dipeptidase (QPP), DPP8, and DPP9; DPP-IV is a key regulator of incretin hormones, but the functions of other family members are unknown.
92	16186403	To determine the importance of selective DPP-IV inhibition for the treatment of diabetes, we tested selective inhibitors of DPP-IV, DPP8/DPP9, or QPP in 2-week rat toxicity studies and in acute dog tolerability studies.
93	16186403	The QPP inhibitor produced reticulocytopenia in rats only, and no toxicities were noted in either species for the selective DPP-IV inhibitor.
94	16186403	The DPP8/9 inhibitor was also shown to attenuate T-cell activation in human in vitro models; a selective DPP-IV inhibitor was inactive in these assays.
95	16186403	Moreover, we found DPP-IV inhibitors that were previously reported to be active in models of immune function to be more potent inhibitors of DPP8/9.
96	16186403	DPP-IV is a member of a family of serine peptidases that includes quiescent cell proline dipeptidase (QPP), DPP8, and DPP9; DPP-IV is a key regulator of incretin hormones, but the functions of other family members are unknown.
97	16186403	To determine the importance of selective DPP-IV inhibition for the treatment of diabetes, we tested selective inhibitors of DPP-IV, DPP8/DPP9, or QPP in 2-week rat toxicity studies and in acute dog tolerability studies.
98	16186403	The QPP inhibitor produced reticulocytopenia in rats only, and no toxicities were noted in either species for the selective DPP-IV inhibitor.
99	16186403	The DPP8/9 inhibitor was also shown to attenuate T-cell activation in human in vitro models; a selective DPP-IV inhibitor was inactive in these assays.
100	16186403	Moreover, we found DPP-IV inhibitors that were previously reported to be active in models of immune function to be more potent inhibitors of DPP8/9.
101	16186403	DPP-IV is a member of a family of serine peptidases that includes quiescent cell proline dipeptidase (QPP), DPP8, and DPP9; DPP-IV is a key regulator of incretin hormones, but the functions of other family members are unknown.
102	16186403	To determine the importance of selective DPP-IV inhibition for the treatment of diabetes, we tested selective inhibitors of DPP-IV, DPP8/DPP9, or QPP in 2-week rat toxicity studies and in acute dog tolerability studies.
103	16186403	The QPP inhibitor produced reticulocytopenia in rats only, and no toxicities were noted in either species for the selective DPP-IV inhibitor.
104	16186403	The DPP8/9 inhibitor was also shown to attenuate T-cell activation in human in vitro models; a selective DPP-IV inhibitor was inactive in these assays.
105	16186403	Moreover, we found DPP-IV inhibitors that were previously reported to be active in models of immune function to be more potent inhibitors of DPP8/9.
106	16980568	The trifluoroacetate salt form of ER-319711, ER-319711-15, inhibited human DPP-IV with an IC(50) value of 0.089 microM, whereas its IC(50) values toward human DPP8 and DPP9 were >100 microM.
107	16980568	ER-319711-15 (1 mg/kg) reduced glucose excursion in an oral glucose tolerance test (OGTT) using Zucker fa/fa rats, with significant increases in plasma insulin and active glucagon-like peptide-1 levels.
108	17034148	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.
109	17034148	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.
110	17034148	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.
111	17034148	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.
112	17194587	More than 20 compounds were evaluated for their in vitro DPP-IV inhibition and selectivity profile over DPP-II, DPP8, and FAP enzymes.
113	17287297	Until now, only recombinant forms of DPP8 and DPP9 have been characterized.
114	17287297	All leukocyte types tested (lymphocytes, monocytes, Jurkat, and U937 cells) were shown to contain similar DPP8/9-specific activities, and DPPII- and DPPIV-specific activities varied considerably.
115	17287297	Subcellular fractionation localized the preponderance of DPP8/9 activity to the cytosol and DPPIV in the membrane fractions.
116	17287297	Until now, only recombinant forms of DPP8 and DPP9 have been characterized.
117	17287297	All leukocyte types tested (lymphocytes, monocytes, Jurkat, and U937 cells) were shown to contain similar DPP8/9-specific activities, and DPPII- and DPPIV-specific activities varied considerably.
118	17287297	Subcellular fractionation localized the preponderance of DPP8/9 activity to the cytosol and DPPIV in the membrane fractions.
119	17287297	Until now, only recombinant forms of DPP8 and DPP9 have been characterized.
120	17287297	All leukocyte types tested (lymphocytes, monocytes, Jurkat, and U937 cells) were shown to contain similar DPP8/9-specific activities, and DPPII- and DPPIV-specific activities varied considerably.
121	17287297	Subcellular fractionation localized the preponderance of DPP8/9 activity to the cytosol and DPPIV in the membrane fractions.
122	17352677	The emergence of glucagon-like peptide 1 (GLP-1) as a well validated approach to the treatment of type 2 diabetes and preclinical validation of dipeptidyl peptidase IV (DPP-4) inhibition as an alternate, oral approach to GLP-1 therapy prompted the initiation of a DPP-4 inhibitor program at Merck in 1999.
123	17352677	The observation that both compounds inhibit the related proline peptidases DPP8 and DPP9 led to the hypothesis that inhibition of DPP8 and/or DPP9 could evoke severe toxicities in preclinical species.
124	17352677	Indeed, the observed toxicities were recapitulated with a selective dual DPP8/9 inhibitor but not with an inhibitor selective for DPP-4.
125	17352677	The emergence of glucagon-like peptide 1 (GLP-1) as a well validated approach to the treatment of type 2 diabetes and preclinical validation of dipeptidyl peptidase IV (DPP-4) inhibition as an alternate, oral approach to GLP-1 therapy prompted the initiation of a DPP-4 inhibitor program at Merck in 1999.
126	17352677	The observation that both compounds inhibit the related proline peptidases DPP8 and DPP9 led to the hypothesis that inhibition of DPP8 and/or DPP9 could evoke severe toxicities in preclinical species.
127	17352677	Indeed, the observed toxicities were recapitulated with a selective dual DPP8/9 inhibitor but not with an inhibitor selective for DPP-4.
128	17352682	This review will mainly focus on proline-specific dipeptidyl peptidases related to DPP IV: fibroblast activation protein (FAP), dipeptidyl peptidase 8 (DPP8), dipeptidyl peptidase 9 (DPP9) and dipeptidyl peptidase II (DPP II).
129	17543192	Dipeptidyl peptidase IV is a serine protease with an indirect role in antihyperglycaemia via degradation of the incretin hormones glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide.
130	17543192	In this study, we have investigated upon selectivity of dipeptidyl peptidase IV compared to two other members of the S9b family, dipeptidyl peptidase 8 and 9, based on kinetic analyses of the pancreatic peptide hormones neuropeptide Y and peptide YY.
131	17543192	We report a striking 250-fold preference for cleavage of neuropeptide Y compared to peptide YY observed for DPP-8/-9, but not for DPP-IV.
132	17543192	Dipeptidyl peptidase IV is a serine protease with an indirect role in antihyperglycaemia via degradation of the incretin hormones glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide.
133	17543192	In this study, we have investigated upon selectivity of dipeptidyl peptidase IV compared to two other members of the S9b family, dipeptidyl peptidase 8 and 9, based on kinetic analyses of the pancreatic peptide hormones neuropeptide Y and peptide YY.
134	17543192	We report a striking 250-fold preference for cleavage of neuropeptide Y compared to peptide YY observed for DPP-8/-9, but not for DPP-IV.
135	17869513	Substitution at the 1- and 3-positions produced increased selectivity for DPP-4 relative to DPP-8 and DPP-9.
136	18223196	BI 1356 was >/=10,000-fold more selective for DPP-4 than DPP-8, DPP-9, amino-peptidases N and P, prolyloligopeptidase, trypsin, plasmin, and thrombin and was 90-fold more selective than for fibroblast activation protein in vitro.
137	18398600	In contrast, ASP8497 did not potently inhibit human DPP8 or DPP9 activity (IC(50)=1,700 nM and 100 nM, respectively) and exhibited selectivity against several proteases, including proline-specific proteases (IC(50)>10 microM).
138	18398600	This was accompanied by increases in the plasma active GLP-1 and insulin levels.
139	18468582	In contrast, ASP8497 did not potently inhibit DPP8 or DPP9 activity (IC(50)>200 nM).
140	18468582	In streptozotocin-nicotinamide-induced diabetic mice, ASP8497 (3 mg/kg) significantly reduced glucose excursion during the oral glucose tolerance test conducted 0.5 and 8.5 h after administration, with increases in plasma insulin and active glucagon-like peptide-1 (GLP-1) levels.
141	19217790	DPP-4, a protease that specifically cleaves dipeptides from proteins and oligopeptides after a penultimate N-terminal proline or alanine, is involved in the degradation of a number of neuropeptides, peptide hormones and cytokines, including the incretins GLP-1 and GIP.
142	19217790	As soon as released from the gut in response to food intake, GLP-1 and GIP exert a potent glucose-dependent insulinotropic action, thereby playing a key role in the maintenance of post-meal glycemic control.
143	19217790	Consequently, inhibiting DPP-4 prolongs the action of GLP-1 and GIP, which in turn improves glucose homeostasis with a low risk of hypoglycemia and potential for disease modification.
144	19217790	Achieving desired selectivity for DPP-4 over other related peptidases such as DPP-8 and DPP-9 (inhibition of which was linked to toxicity in animal studies) and long-acting potential for maximal efficacy (particularly in more severe diabetic patients) were the major challenges.
145	19439267	By Ki measurement, 1G244 is 15- and 8-fold more potent against DPP8 and DPP9, respectively, than the "DPP8/9 inhibitor".
146	19482472	The inhibitors show good to moderate biochemical potency against DPP4 and display distinct selectivity profiles towards DPP7, DPP8 and DPP9 depending on their substitution.
147	19689275	Since implicated in the regulation of the biological activity of hormones and chemokines, such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, DPP4 inhibition offers a new potential therapeutic approach for type 2 diabetes mellitus, as monotherapy and adjunct therapy to other oral agents.
148	19689275	The clinical use of presently available orally active inhibitors of DPP4, however, has been associated with side effects that have been in part attributed to the inhibition of related serine proteases, such as DPP8 and DPP9.
149	19837468	Dipeptidyl peptidase (DPP)-4 is a member of the S9b serine protease family, which also includes DPP8 and DPP9.
150	19837468	Recent data suggest that the early DPP4-specific inhibitors might also bind DPP8 and DPP9, thus exerting their effects through non-specific binding.
151	19837468	Dipeptidyl peptidase (DPP)-4 is a member of the S9b serine protease family, which also includes DPP8 and DPP9.
152	19837468	Recent data suggest that the early DPP4-specific inhibitors might also bind DPP8 and DPP9, thus exerting their effects through non-specific binding.
153	21262219	TS-021 exhibited significant inhibition selectivity against DPP-8 (>600 fold), DPP-9 (>1200 fold) and other peptidases examined (>15,000 fold).
154	21262219	In Zucker fatty (fa/fa) rats, a rat model of obesity and impaired glucose tolerance, the oral administration of TS-021 resulted in the suppression of plasma DPP-IV activity and an increase in the active form of GLP-1.
155	21996520	7-Oxopyrrolopyridine-derived DPP4 inhibitors-mitigation of CYP and hERG liabilities via introduction of polar functionalities in the active site.
156	21996520	Compound (+)-3t, with a K(i) against DPP4, DPP8, and DPP9 of 0.37 nM, 2.2, and 5.7 μM, respectively, showed a significant improvement in insulin response after single doses of 3 and 10 μmol/kg in ob/ob mice.
157	22994702	Among these, compounds 7j, 7q, and 7s displayed good dipeptidyl peptidase-4 activity and excellent selectivity versus other proteases including dipeptidyl peptidase-8, dipeptidyl peptidase-9, and FAP.
158	23358258	Compounds H4 and H9 showed good DPP-4 inhibition and more than 100-fold selectivity over DPP-7 and DPP-8.
159	23608773	However, until now the expression and role of other DPPs such as DPP8 and DPP9 in atherosclerosis is completely unknown.
160	23608773	In contrast, DPP8 and DPP9 were abundantly present in macrophage-rich regions of plaques.
161	23608773	During monocyte to macrophage differentiation, DPP9 was upregulated both in pro-inflammatory M1 (3.7 ± 0.3-fold increase) and anti-inflammatory M2 macrophages (3.7 ± 0.4-fold increase) whereas DPP8 expression remained unchanged.
162	23608773	Inhibition of DPP8/9 activity with compound 1G244 reduced activation of M1 macrophages (IL-6 88 ± 16 vs. 146 ± 19 pg/ml; TNFα 3.8 ± 1.0 vs. 6.6 ± 1.9 ng/ml in treated vs. untreated cells), but not of M2 macrophages.
163	23608773	Likewise, DPP9 silencing reduced TNFα and IL-6 secretion, pointing to a DPP9-mediated effect of the inhibitor.
164	23608773	However, until now the expression and role of other DPPs such as DPP8 and DPP9 in atherosclerosis is completely unknown.
165	23608773	In contrast, DPP8 and DPP9 were abundantly present in macrophage-rich regions of plaques.
166	23608773	During monocyte to macrophage differentiation, DPP9 was upregulated both in pro-inflammatory M1 (3.7 ± 0.3-fold increase) and anti-inflammatory M2 macrophages (3.7 ± 0.4-fold increase) whereas DPP8 expression remained unchanged.
167	23608773	Inhibition of DPP8/9 activity with compound 1G244 reduced activation of M1 macrophages (IL-6 88 ± 16 vs. 146 ± 19 pg/ml; TNFα 3.8 ± 1.0 vs. 6.6 ± 1.9 ng/ml in treated vs. untreated cells), but not of M2 macrophages.
168	23608773	Likewise, DPP9 silencing reduced TNFα and IL-6 secretion, pointing to a DPP9-mediated effect of the inhibitor.
169	23608773	However, until now the expression and role of other DPPs such as DPP8 and DPP9 in atherosclerosis is completely unknown.
170	23608773	In contrast, DPP8 and DPP9 were abundantly present in macrophage-rich regions of plaques.
171	23608773	During monocyte to macrophage differentiation, DPP9 was upregulated both in pro-inflammatory M1 (3.7 ± 0.3-fold increase) and anti-inflammatory M2 macrophages (3.7 ± 0.4-fold increase) whereas DPP8 expression remained unchanged.
172	23608773	Inhibition of DPP8/9 activity with compound 1G244 reduced activation of M1 macrophages (IL-6 88 ± 16 vs. 146 ± 19 pg/ml; TNFα 3.8 ± 1.0 vs. 6.6 ± 1.9 ng/ml in treated vs. untreated cells), but not of M2 macrophages.
173	23608773	Likewise, DPP9 silencing reduced TNFα and IL-6 secretion, pointing to a DPP9-mediated effect of the inhibitor.
174	23608773	However, until now the expression and role of other DPPs such as DPP8 and DPP9 in atherosclerosis is completely unknown.
175	23608773	In contrast, DPP8 and DPP9 were abundantly present in macrophage-rich regions of plaques.
176	23608773	During monocyte to macrophage differentiation, DPP9 was upregulated both in pro-inflammatory M1 (3.7 ± 0.3-fold increase) and anti-inflammatory M2 macrophages (3.7 ± 0.4-fold increase) whereas DPP8 expression remained unchanged.
177	23608773	Inhibition of DPP8/9 activity with compound 1G244 reduced activation of M1 macrophages (IL-6 88 ± 16 vs. 146 ± 19 pg/ml; TNFα 3.8 ± 1.0 vs. 6.6 ± 1.9 ng/ml in treated vs. untreated cells), but not of M2 macrophages.
178	23608773	Likewise, DPP9 silencing reduced TNFα and IL-6 secretion, pointing to a DPP9-mediated effect of the inhibitor.
179	23671024	Liver microsome stability and cytochrome P450 metabolic tests were performed on this series, revealing undesirable pharmacokinetic profiles for the triazole compounds.
180	23671024	Based on its enzyme activity, metabolic stability, and selectivity over DPP8 and DPP9, we selected compound 21 r for further study of its in vivo effects in mice using an oral glucose tolerance test (OGTT).
181	23938053	Furthermore, the 4-fluorobenzyl substituted phenylalanine derivative 6g not only displayed the potent DPP-4 inhibition with an IC50 value of 3.79 nM, but also showed better selectivity against DPP-4 over other related enzymes including DPP-7, DPP-8, and DPP-9.
182	23972441	Optimization of the series provided inhibitors with good DPP-4 potency and selectivity over other peptidases (QPP, DPP8, and FAP).