Details of the Target

General Information of Target

Target ID LDTP07728
Target Name Dipeptidyl peptidase 8 (DPP8)
Gene Name DPP8
Gene ID 54878
Synonyms
DPRP1; Dipeptidyl peptidase 8; DP8; EC 3.4.14.5; Dipeptidyl peptidase IV-related protein 1; DPRP-1; Dipeptidyl peptidase VIII; DPP VIII; Prolyl dipeptidase DPP8
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MWKRSEQMKIKSGKCNMAAAMETEQLGVEIFETADCEENIESQDRPKLEPFYVERYSWSQ
LKKLLADTRKYHGYMMAKAPHDFMFVKRNDPDGPHSDRIYYLAMSGENRENTLFYSEIPK
TINRAAVLMLSWKPLLDLFQATLDYGMYSREEELLRERKRIGTVGIASYDYHQGSGTFLF
QAGSGIYHVKDGGPQGFTQQPLRPNLVETSCPNIRMDPKLCPADPDWIAFIHSNDIWISN
IVTREERRLTYVHNELANMEEDARSAGVATFVLQEEFDRYSGYWWCPKAETTPSGGKILR
ILYEENDESEVEIIHVTSPMLETRRADSFRYPKTGTANPKVTFKMSEIMIDAEGRIIDVI
DKELIQPFEILFEGVEYIARAGWTPEGKYAWSILLDRSQTRLQIVLISPELFIPVEDDVM
ERQRLIESVPDSVTPLIIYEETTDIWINIHDIFHVFPQSHEEEIEFIFASECKTGFRHLY
KITSILKESKYKRSSGGLPAPSDFKCPIKEEIAITSGEWEVLGRHGSNIQVDEVRRLVYF
EGTKDSPLEHHLYVVSYVNPGEVTRLTDRGYSHSCCISQHCDFFISKYSNQKNPHCVSLY
KLSSPEDDPTCKTKEFWATILDSAGPLPDYTPPEIFSFESTTGFTLYGMLYKPHDLQPGK
KYPTVLFIYGGPQVQLVNNRFKGVKYFRLNTLASLGYVVVVIDNRGSCHRGLKFEGAFKY
KMGQIEIDDQVEGLQYLASRYDFIDLDRVGIHGWSYGGYLSLMALMQRSDIFRVAIAGAP
VTLWIFYDTGYTERYMGHPDQNEQGYYLGSVAMQAEKFPSEPNRLLLLHGFLDENVHFAH
TSILLSFLVRAGKPYDLQIYPQERHSIRVPESGEHYELHLLHYLQENLGSRIAALKVI
Target Type
Clinical trial
Target Bioclass
Enzyme
Family
Peptidase S9B family, DPPIV subfamily
Subcellular location
Cytoplasm
Function
Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2. Acts as a key inhibitor of caspase-1-dependent monocyte and macrophage pyroptosis in resting cells by preventing activation of NLRP1 and CARD8. 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. 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.
TTD ID
T15855
Uniprot ID
Q6V1X1
DrugMap ID
TTJGLZF
Ensemble ID
ENST00000300141.11
HGNC ID
HGNC:16490
ChEMBL ID
CHEMBL4657

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 5 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C596(1.59)  LDD3331  [1]
4-Iodoacetamidophenylacetylene
 Probe Info  		N.A.  LDD0038  [2]
IA-alkyne
 Probe Info  		C221(0.00); C596(0.00)  LDD0036  [2]
Lodoacetamide azide
 Probe Info  		C221(0.00); C611(0.00); C596(0.00); C286(0.00)  LDD0037  [2]
Acrolein
 Probe Info  		N.A.  LDD0217  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0215  AC10 HEK-293T C211(0.98)  LDD1508  [4]
 LDCM0259  AC14 HEK-293T C611(1.17)  LDD1512  [4]
 LDCM0277  AC18 HEK-293T C211(1.00)  LDD1516  [4]
 LDCM0279  AC2 HEK-293T C211(1.02)  LDD1518  [4]
 LDCM0282  AC22 HEK-293T C611(1.56)  LDD1521  [4]
 LDCM0286  AC26 HEK-293T C211(1.08)  LDD1525  [4]
 LDCM0291  AC30 HEK-293T C611(0.87)  LDD1530  [4]
 LDCM0295  AC34 HEK-293T C211(0.88)  LDD1534  [4]
 LDCM0299  AC38 HEK-293T C611(0.90)  LDD1538  [4]
 LDCM0304  AC42 HEK-293T C211(1.13)  LDD1543  [4]
 LDCM0308  AC46 HEK-293T C611(1.32)  LDD1547  [4]
 LDCM0313  AC50 HEK-293T C211(1.02)  LDD1552  [4]
 LDCM0317  AC54 HEK-293T C611(1.04)  LDD1556  [4]
 LDCM0321  AC58 HEK-293T C211(1.06)  LDD1560  [4]
 LDCM0323  AC6 HEK-293T C611(0.97)  LDD1562  [4]
 LDCM0326  AC62 HEK-293T C611(0.87)  LDD1565  [4]
 LDCM0108  Chloroacetamide HeLa N.A.  LDD0222  [3]
 LDCM0368  CL10 HEK-293T C611(1.09)  LDD1572  [4]
 LDCM0405  CL18 HEK-293T C211(0.89)  LDD1609  [4]
 LDCM0410  CL22 HEK-293T C611(1.30)  LDD1614  [4]
 LDCM0419  CL30 HEK-293T C211(1.18)  LDD1623  [4]
 LDCM0423  CL34 HEK-293T C611(1.35)  LDD1627  [4]
 LDCM0432  CL42 HEK-293T C211(0.98)  LDD1636  [4]
 LDCM0436  CL46 HEK-293T C611(0.86)  LDD1640  [4]
 LDCM0445  CL54 HEK-293T C211(1.28)  LDD1648  [4]
 LDCM0449  CL58 HEK-293T C611(1.21)  LDD1652  [4]
 LDCM0451  CL6 HEK-293T C211(0.85)  LDD1654  [4]
 LDCM0458  CL66 HEK-293T C211(0.89)  LDD1661  [4]
 LDCM0463  CL70 HEK-293T C611(1.03)  LDD1666  [4]
 LDCM0471  CL78 HEK-293T C211(1.14)  LDD1674  [4]
 LDCM0476  CL82 HEK-293T C611(1.30)  LDD1679  [4]
 LDCM0485  CL90 HEK-293T C211(1.16)  LDD1688  [4]
 LDCM0489  CL94 HEK-293T C611(1.06)  LDD1692  [4]
 LDCM0022  KB02 HEK-293T C611(1.14)  LDD1492  [4]
 LDCM0023  KB03 HEK-293T C611(1.09)  LDD1497  [4]
 LDCM0024  KB05 MKN-1 C596(1.59)  LDD3331  [1]

The Interaction Atlas With This Target

The Drug(s) Related To This Target

Phase 3
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Talabostat Small molecular drug D0FQ2U
Investigative
Click To Hide/Show 3 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
1g244 Small molecular drug D0CP1J
Pmid15664838c18 Small molecular drug D02RDY
Pmid20684603c24dd Small molecular drug D08NMS
Patented
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Thiomorpholine Derivative 1 Small molecular drug D06HJX
Thiomorpholine Derivative 2 Small molecular drug D0D4BP

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
3 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
4 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402