Protein Information

General Information of the Protein

Protein ID	PT00975
Protein Name	Dipeptidyl peptidase 8
Secondarily Protein Name	Dipeptidyl peptidase IV-related protein 1 Dipeptidyl peptidase VIII Prolyl dipeptidase DPP8
Gene Name	DPP8
Secondarily Gene Name	DPRP1 MSTP097 MSTP135 MSTP141
Sequence	MWKRSEQMKIKSGKCNMAAAMETEQLGVEIFETADCEENIESQDRPKLEPFYVERYSWSQLKKLLADTRKYHGYMMAKAPHDFMFVKRNDPDGPHSDRIYYLAMSGENRENTLFYSEIPKTINRAAVLMLSWKPLLDLFQATLDYGMYSREEELLRERKRIGTVGIASYDYHQGSGTFLFQAGSGIYHVKDGGPQGFTQQPLRPNLVETSCPNIRMDPKLCPADPDWIAFIHSNDIWISNIVTREERRLTYVHNELANMEEDARSAGVATFVLQEEFDRYSGYWWCPKAETTPSGGKILRILYEENDESEVEIIHVTSPMLETRRADSFRYPKTGTANPKVTFKMSEIMIDAEGRIIDVIDKELIQPFEILFEGVEYIARAGWTPEGKYAWSILLDRSQTRLQIVLISPELFIPVEDDVMERQRLIESVPDSVTPLIIYEETTDIWINIHDIFHVFPQSHEEEIEFIFASECKTGFRHLYKITSILKESKYKRSSGGLPAPSDFKCPIKEEIAITSGEWEVLGRHGSNIQVDEVRRLVYFEGTKDSPLEHHLYVVSYVNPGEVTRLTDRGYSHSCCISQHCDFFISKYSNQKNPHCVSLYKLSSPEDDPTCKTKEFWATILDSAGPLPDYTPPEIFSFESTTGFTLYGMLYKPHDLQPGKKYPTVLFIYGGPQVQLVNNRFKGVKYFRLNTLASLGYVVVVIDNRGSCHRGLKFEGAFKYKMGQIEIDDQVEGLQYLASRYDFIDLDRVGIHGWSYGGYLSLMALMQRSDIFRVAIAGAPVTLWIFYDTGYTERYMGHPDQNEQGYYLGSVAMQAEKFPSEPNRLLLLHGFLDENVHFAHTSILLSFLVRAGKPYDLQIYPQERHSIRVPESGEHYELHLLHYLQENLGSRIAALKVI Show/Hide
Organism	Homo sapiens, Human
Protein Classification	Enzyme > Protease > Serine protease > Serine protease SC clan > Serine protease S9B subfamily
Function	Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2 (PubMed:11012666, PubMed:12534281, PubMed:12662155, PubMed:15039077, PubMed:15664838, PubMed:20536396, PubMed:29382749). Acts as a key inhibitor of caspase-1-dependent monocyte and macrophage pyroptosis in resting cells by preventing activation of NLRP1 and CARD8 (PubMed:27820798, PubMed:29967349, PubMed:32796818). Sequesters the cleaved C-terminal part of NLRP1 and CARD8, which respectively constitute the active part of the NLRP1 and CARD8 inflammasomes, in a ternary complex, thereby preventing their oligomerization and activation (PubMed:34019797, PubMed:33731929, PubMed:33731932). The dipeptidyl peptidase activity is required to suppress NLRP1 and CARD8; however, neither NLRP1 nor CARD8 are bona fide substrates of DPP8, suggesting the existence of substrate(s) required for NLRP1 and CARD8 inhibition (By similarity). Show/Hide
Uniprot ID	Primary ID: Q6V1X1 Secondarily ID: Q7Z4C8 Q7Z4D3 Q7Z4E1 Q8IWG7 Q8NEM5 Q96JX1 Q9HBM2 Q9HBM3 Q9HBM4 Q9HBM5 Q9NXF4 Show/Hide
Ensembl ID	ENSG00000074603
HGNC ID	HGNC:16490
Subcellular Location	Cytoplasm

Map of Molecular Bioactivity Related to the Protein

Map of Molecular Bioactivity Related to the Protein Protein Cell Line Compound Bioactivity Value: <= 0.1 μM > 0.1 μM and <= 10 μM > 10 μM Imprecise Activity

Table of Molecular Bioactivities Related to the Protein

Cell Line ID: CL000023 , BTI-Tn-5B1-4

Cell Line Info

Compound ID	Compound Name	Compound Formula
CP0077736 Compound Info	(2S)-1-[(2S)-2-amino-4-{4-[bis(4-fluorophenyl)methyl]piperazin-1-yl}-4-oxobutanoyl]pyrrolidine-2-carbonitrile Show/Hide	C26H29F2N5O2	1
1	IC50 = 14 nM Bioactivity Info	TI LI LO TS
CP0138655 Compound Info	(2S,3R)-2-amino-1-(isoindolin-2-yl)-3-methylpentan-1-one Show/Hide	C14H20N2O	1
1	IC50 = 150 nM Bioactivity Info	TI LI LO TS
CP0377209 Compound Info	(S)-1-((S)-2-amino-5-(1-oxoisoindolin-2-yl)pentanoyl)pyrrolidine-2-carbonitrile Show/Hide	C18H22N4O2	1
1	IC50 = 360 nM Bioactivity Info	TI LI LO TS
CP0417860 Compound Info	(2R)-1-{(2S, 4S)-4-[2-(1,3-Dihydroisoindol-2-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carbonyl}pyrrolidine-2-boronic Acid Show/Hide	C19H24BN3O5	1
1	IC50 = 500 nM Bioactivity Info	TI LI LO TS
CP0067540 Compound Info	(R)-1-(2-(1-naphthamido)acetyl)pyrrolidin-2-ylboronic acid Show/Hide	C17H19BN2O4	1
1	IC50 = 3700 nM Bioactivity Info	TI LI LO TS
CP0172402 Compound Info	(R)-1-(2-(1-oxoisoindolin-2-yl)acetyl)pyrrolidin-2-ylboronic acid Show/Hide	C14H17BN2O4	1
1	IC50 = 11000 nM Bioactivity Info	TI LI LO TS
CP0048107 Compound Info	(2S)-1-{2-[(3-hydroxyadamantan-1-yl)amino]acetyl}pyrrolidine-2-carbonitrile Show/Hide	C17H25N3O2	1
1	IC50 = 14000 nM Bioactivity Info	TI LI LO TS
CP0007316 Compound Info	(1R)-3-oxo-3-[3-(trifluoroethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorobenzyl)propylamine Show/Hide	C16H15F6N5O	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0089998 Compound Info	(2S)-1-({(2S,4S)-4-[2-(1,3-Dihydro-2H-isoindol-2-yl)-2-oxoethyl]-5-oxopyrrolidin-2-yl}carbonyl)-4,4-difluoropyrrolidine-2-carbonitrile Show/Hide	C20H20F2N4O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0117955 Compound Info	(S)-N-(2-(2-cyanopyrrolidin-1-yl)-2-oxoethyl)-1-naphthamide Show/Hide	C18H17N3O2	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0280292 Compound Info	2-(S)-Amino-4-(2-chloro-benzylamino)-1-piperidin-1-yl-butan-1-one Show/Hide	C16H24ClN3O	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0365775 Compound Info	(2S,4S)-1-({(2S,4S)-4-[2-(1,3-Dihydro-2H-isoindol-2-yl)-2-oxoethyl]-5-oxopyrrolidin-2-yl}carbonyl)-4-fluoropyrrolidine-2-carbonitrile Show/Hide	C20H21FN4O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0377210 Compound Info	(S)-1-((2S,4R)-4-(2-(isoindolin-2-yl)-2-oxoethyl)-5-oxopyrrolidine-2-carbonyl)pyrrolidine-2-carbonitrile Show/Hide	C20H22N4O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0377211 Compound Info	(2S)-1-[{(2S,4S)-5-Oxo-4-(2-oxo-2-(piperidin-1-yl)ethyl)pyrrolidine-2-yl}carbonyl]pyrrolidine-2-carbonitrile Show/Hide	C17H24N4O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0377217 Compound Info	(2S)-1-{(2S,4S)-4-[2-(1,3-Dihydroisoindol-2-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carbonyl}pyrrolidine-2-carboxylic Acid tert-Butylamide Show/Hide	C24H32N4O4	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0377219 Compound Info	(2S)-1-({(2S,4S)-4-[2-[4-(Pyridine-4-yl)-piperazin-1-yl]-2-oxoethyl]-5-oxopyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile Show/Hide	C21H26N6O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0386927 Compound Info	(2S)-1-{(2S,4S)-4-[2-(5-Fluoro-1,3-dihydroisoindol-2-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carbonyl}pyrrolidine-2-carbonitrile Show/Hide	C20H21FN4O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0386928 Compound Info	(2S)-1-({(2S,4S)-4-[2-[4-(4-Chlorophenyl)-3,6-dihydropyridin-1(2H)-yl]-2-oxoethyl]-5-oxopyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile Show/Hide	C23H25ClN4O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0398656 Compound Info	(2S)-1-({(2S,4S)-4-[2-(5-Chloro-1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]-5-oxopyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile Show/Hide	C20H21ClN4O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0398665 Compound Info	(2S)-1-({(2S,4S)-4-[2-(1,3-Dihydro-2H-isoquinol-2-yl)-2-oxoethyl]-5-oxopyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile Show/Hide	C21H24N4O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0405590 Compound Info	(3S,5S)-3-[2-(1,3-Dihydro-2H-isoindol-2-yl)-2-oxoethyl]-5-(1,3-thiazolidin-3-ylcarbonyl)pyrrolidin-2-one Show/Hide	C18H21N3O3S	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0405591 Compound Info	(3S,5S)-3-[2-(1,3-Dihydroisoindol-2-yl)-2-oxoethyl]-5-(pyrrolidine-1-carbonyl)pyrrolidin-2-one Show/Hide	C19H23N3O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0405592 Compound Info	(2S)-1-({(2S,4S)-4-[2-(1,3-Dihydroisoindol-2-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carbonyl}pyrrolidine-2-carboxylic Acid Amide Show/Hide	C20H24N4O4	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0405593 Compound Info	(2S)-1-{(2S, 4S)-4-[2-(1,3-Dihydroisoindol-2-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carbonyl}pyrrolidine-2-carbonitrile Show/Hide	C20H22N4O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0416406 Compound Info	(2S)-1-({(2S,4S)-5-Oxo-4-[2-oxo-2-(pyrrolidin-1-yl)ethyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile Show/Hide	C16H22N4O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0416420 Compound Info	2S)-1-({(2S,4S)-5-oxo-4-[2-Oxo-[2-(trifluoromethyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl]ethyl]pyrrolidin-2-yl}carbonyl)-pyrrolidine-2-carbonitrile Show/Hide	C19H21F3N6O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0417856 Compound Info	(2S)-1-({(2S,4S)-5-Oxo-4-[2-oxo-2-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]ethyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile Show/Hide	C18H20F3N7O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0417859 Compound Info	(2S,4S)-1-{(2S,4S)-4-[2-(5-Chloro-1,3-dihydroisoindol-2-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carbonyl}-4-fluoropyrrolidine-2-carbonitrile Show/Hide	C20H20ClFN4O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0469898 Compound Info	2-[(3S,5S)-5-{[(2S)-2-Cyanopyrrolidin-1-yl]carbonyl}-2-oxopyrrolidin-3-yl]-N-phenylacetamide Show/Hide	C18H20N4O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0473229 Compound Info	2S)-1-({(2S,4S)-4-[2-(6,7-Dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-oxoethyl]-5-oxopyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile Show/Hide	C19H22N4O3S	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0477589 Compound Info	(2S)-1-({(2S,4S)-4-[2-(5-Trifluoromethyl-1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]-5-oxopyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile Show/Hide	C21H21F3N4O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0507612 Compound Info	(2S)-1-({(2S,4S)-4-[2-[4-(4-Fluorophenyl)piperazin-1-yl]-2-oxoethyl]-5-oxopyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile Show/Hide	C22H26FN5O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0903652 Compound Info	(2S)-1-((2S)-4-(2-(isoindolin-2-yl)-2-oxoethyl)-5-oxopyrrolidine-2-carbonyl)pyrrolidine-2-carbonitrile Show/Hide	C20H22N4O3	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS

Cell Line ID: CL000053 , COS-7

Cell Line Info

Cell Line ID: CL000025 , HEK-293T

Cell Line Info

Cell Line ID: CL000006 , HEK293

Cell Line Info

Cell Line ID: CL000131 , HEK293-F

Cell Line Info

Cell Line ID: CL000013 , Sf9

Cell Line Info

Biochemical Assays

Compound ID	Compound Name	Compound Formula
CP0048107 Compound Info	(2S)-1-{2-[(3-hydroxyadamantan-1-yl)amino]acetyl}pyrrolidine-2-carbonitrile Show/Hide	C17H25N3O2	11
1	IC50 = 1.85 nM
2	IC50 = 1100 nM
3	IC50 = 1400 nM
4	IC50 = 1520 nM
5	IC50 = 3820 nM
6	IC50 = 9000 nM
7	IC50 = 14000 nM
8	IC50 = 14200 nM
9	IC50 = 14219 nM
10	Ki = 810 nM
11	Ki = 1342 nM
CP0067537 Compound Info	(R)-1-((S)-2-amino-3-methylbutanoyl)pyrrolidin-2-ylboronic acid Show/Hide	C9H19BN2O3	2
1	IC50 = 5.5 nM
2	IC50 = 17 nM
CP0052252 Compound Info	(2S,4S)-1-((2S,3R)-2-amino-3-methylpentanoyl)-4-azidopyrrolidine-2-carbonitrile Show/Hide	C11H18N6O	1
1	IC50 = 11 nM
CP0140807 Compound Info	(2S)-2-amino-4-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]-1-(1,3-dihydroisoindol-2-yl)butane-1,4-dione Show/Hide	C29H30F2N4O2	2
1	IC50 = 12 nM
2	IC50 = 14 nM
CP0077736 Compound Info	(2S)-1-[(2S)-2-amino-4-{4-[bis(4-fluorophenyl)methyl]piperazin-1-yl}-4-oxobutanoyl]pyrrolidine-2-carbonitrile Show/Hide	C26H29F2N5O2	1
1	IC50 = 16 nM
CP0138655 Compound Info	(2S,3R)-2-amino-1-(isoindolin-2-yl)-3-methylpentan-1-one Show/Hide	C14H20N2O	2
1	IC50 = 120 nM
2	IC50 = 122 nM
CP0231981 Compound Info	(R)-1-(2-aminoacetyl)pyrrolidin-2-ylboronic acid Show/Hide	C6H13BN2O3	1
1	IC50 = 180 nM
CP0099440 Compound Info	(R)-1-((S)-2-amino-3-methylbutanamido)ethylboronic acid Show/Hide	C7H17BN2O3	1
1	IC50 = 670 nM
CP0067540 Compound Info	(R)-1-(2-(1-naphthamido)acetyl)pyrrolidin-2-ylboronic acid Show/Hide	C17H19BN2O4	1
1	IC50 = 1200 nM
CP0007316 Compound Info	(1R)-3-oxo-3-[3-(trifluoroethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorobenzyl)propylamine Show/Hide	C16H15F6N5O	10
1	IC50 = 1820 nM
2	IC50 = 19000 nM
3	IC50 = 32000 nM
4	IC50 = 32800 nM
5	IC50 = 48000 nM
6	IC50 = 51000 nM
7	IC50 = 69000 nM
8	IC50 > 20000 nM
9	IC50 > 50000 nM
10	IC50 > 100000 nM
CP0053608 Compound Info	2-({6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl}methyl)benzonitrile Show/Hide	C18H21N5O2	3
1	IC50 > 100 nM
2	IC50 > 25000 nM
3	IC50 > 50000 nM
CP0064961 Compound Info	MK-3102 Show/Hide	C17H20F2N4O3S	1
1	IC50 > 67000 nM
CP0059208 Compound Info	(2R,3S,5R)-2-(2,5-difluorophenyl)-5-(4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-5-yl)oxan-3-amine Show/Hide	C16H18F2N4O	1
1	IC50 > 100000 nM
CP0354373 Compound Info	2-[[4-[(3R)-3-aminopiperidin-1-yl]-3-but-2-ynyl-2,6-dioxopyrimidin-1-yl]methyl]-6-fluorobenzoic acid Show/Hide	C21H23FN4O4	1
1	IC50 > 100000 nM

Clinical Information about the Protein

Target 1 ( Dipeptidyl peptidase 8 (DPP-8) )

Target Type	Clinical trial Target
Disease	1 Target-related Disease				1
1	Constitutional neutropenia [ICD-11: 4B00.0]
Clinical Trial Drug(s)	1 Clinical Trial Drug				1
1	Talabostat	Drug Info	Phase 3	Constitutional neutropenia

Cite

About MolBiC

Correspondence

Prof. Feng ZHU

Prof. Leo, Lianyi Han