Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTQ4ESF)

• DTT Name: Calgranulin D (S100A12)
• Synonyms: S100 calcium-binding protein A12; Protein S100-A12; P6; Neutrophil S100 protein; Migration inhibitory factor-related protein 6; MRP-6; Extracellular newly identified RAGE-binding protein; EN-RAGE; Calgranulin-C; Calcium-binding protein in amniotic fluid 1; CGRP; CAGC; CAAF1
• Gene Name: S100A12
• DTT Type: Clinical trial target; [1]
• BioChemical Class: S100 calcium-binding protein
• UniProt ID: S10AC_HUMAN
• TTD ID: T07247
• Sequence:
  MTKLEEHLEGIVNIFHQYSVRKGHFDTLSKGELKQLLTKELANTIKNIKDKAVIDEIFQG
  LDANQDEQVDFQEFISLVAIALKAAHYHTHKE
• Function: Its proinflammatory activity involves recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to receptor for advanced glycation endproducts (AGER). Binding to AGER activates the MAP-kinase and NF-kappa-B signaling pathways leading to production of proinflammatory cytokines and up-regulation of cell adhesion molecules ICAM1 and VCAM1. Acts as a monocyte and mast cell chemoattractant. Can stimulate mast cell degranulation and activation which generates chemokines, histamine and cytokines inducing further leukocyte recruitment to the sites of inflammation. Can inhibit the activity of matrix metalloproteinases; MMP2, MMP3 and MMP9 by chelating Zn(2+) from their active sites. Possesses filariacidal and filariastatic activity. Calcitermin possesses antifungal activity against C. albicans and is also active against E. coli and P. aeruginosa but not L. monocytogenes and S. aureus. S100A12 is a calcium-, zinc- and copper-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response.
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Advanced glycosylation endproduct receptor signaling (R-HSA-879415)
  TRAF6 mediated NF-kB activation (R-HSA-933542)
  TAK1-dependent IKK and NF-kappa-B activation (R-HSA-445989)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Atogepant	DMZGKXW	Migraine	8A80	Approved	[1]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)