Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT4LM0E)

• DTT Name: Progranulin (PGRN)
• Synonyms: Proepithelin; PGRN; PEPI; PCDGF; PC cell-derived growth factor; Granulin precursor; Glycoprotein of 88 Kda; Glycoprotein 88; GP88; Epithelin precursor; Acrogranin
• Gene Name: GRN
• DTT Type: Literature-reported target; [1]
• UniProt ID: GRN_HUMAN
• TTD ID: T45182
• Sequence:
  MWTLVSWVALTAGLVAGTRCPDGQFCPVACCLDPGGASYSCCRPLLDKWPTTLSRHLGGP
  CQVDAHCSAGHSCIFTVSGTSSCCPFPEAVACGDGHHCCPRGFHCSADGRSCFQRSGNNS
  VGAIQCPDSQFECPDFSTCCVMVDGSWGCCPMPQASCCEDRVHCCPHGAFCDLVHTRCIT
  PTGTHPLAKKLPAQRTNRAVALSSSVMCPDARSRCPDGSTCCELPSGKYGCCPMPNATCC
  SDHLHCCPQDTVCDLIQSKCLSKENATTDLLTKLPAHTVGDVKCDMEVSCPDGYTCCRLQ
  SGAWGCCPFTQAVCCEDHIHCCPAGFTCDTQKGTCEQGPHQVPWMEKAPAHLSLPDPQAL
  KRDVPCDNVSSCPSSDTCCQLTSGEWGCCPIPEAVCCSDHQHCCPQGYTCVAEGQCQRGS
  EIVAGLEKMPARRASLSHPRDIGCDQHTSCPVGQTCCPSLGGSWACCQLPHAVCCEDRQH
  CCPAGYTCNVKARSCEKEVVSAQPATFLARSPHVGVKDVECGEGHFCHDNQTCCRDNRQG
  WACCPYRQGVCCADRRHCCPAGFRCAARGTKCLRREAPRWDAPLRDPALRQLL
• Function: Secreted proteins that act as key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation. Functions as regulator of proteins trafficking to lysosome and activity of lysosomal enzymes. Facilitates also the acidification of lysosomes, causing degradation of mature CTSD by CTSB. In addition, functions as wound-related growth factor that acts directly on dermal fibroblasts and endothelial cells to promote division, migration and the formation of capillary-like tubule structure (By similarity). Also promotes epithelial cell proliferation by blocking TNF-mediated neutrophil activation preventing release of oxidants and proteases. Moreover, modulates inflammation in neuron by preserving neuron survival, axonal outgrowth and neuronal integrity.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DTT

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DNL593	DMMSA9Y	Frontotemporal dementia	6D83	Phase 1/2	[2]
PBFT02	DMMXU5U	Frontotemporal dementia	6D83	Phase 1/2	[3]
PR-006	DMM7HKG	Frontotemporal dementia	6D83	Phase 1/2	[4]

References

• [1] Granulin-epithelin precursor renders hepatocellular carcinoma cells resistant to natural killer cytotoxicity. Cancer Immunol Res. 2014 Dec;2(12):1209-19.
• [2] Clinical pipeline report, company report or official report of Denali
• [3] Clinical pipeline report, company report or official report of Passage Bio
• [4] Clinical pipeline report, company report or official report of Prevail Therapeutics