Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT2L4TV)

• DTT Name: SERPINA1 messenger RNA (SERPINA1 mRNA)
• Synonyms: Alpha-1 protease inhibitor; Alpha-1-antiproteinase; Serpin A1
• Gene Name: SERPINA1
• DTT Type: Clinical trial target; [1]
• UniProt ID: A1AT_HUMAN
• TTD ID: T65941
• Sequence:
  MPSSVSWGILLLAGLCCLVPVSLAEDPQGDAAQKTDTSHHDQDHPTFNKITPNLAEFAFS
  LYRQLAHQSNSTNIFFSPVSIATAFAMLSLGTKADTHDEILEGLNFNLTEIPEAQIHEGF
  QELLRTLNQPDSQLQLTTGNGLFLSEGLKLVDKFLEDVKKLYHSEAFTVNFGDTEEAKKQ
  INDYVEKGTQGKIVDLVKELDRDTVFALVNYIFFKGKWERPFEVKDTEEEDFHVDQVTTV
  KVPMMKRLGMFNIQHCKKLSSWVLLMKYLGNATAIFFLPDEGKLQHLENELTHDIITKFL
  ENEDRRSASLHLPKLSITGTYDLKSVLGQLGITKVFSNGADLSGVTEEAPLKLSKAVHKA
  VLTIDEKGTEAAGAMFLEAIPMSIPPEVKFNKPFVFLMIEQNTKSPLFMGKVVNPTQK
• Function: Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The aberrant form inhibits insulin-induced NO synthesis in platelets, decreases coagulation time and has proteolytic activity against insulin and plasmin.
• KEGG Pathway: Complement and coagulation cascades (hsa04610)
• Reactome Pathway:
  COPII-mediated vesicle transport (R-HSA-204005)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Cargo concentration in the ER (R-HSA-5694530)
  Neutrophil degranulation (R-HSA-6798695)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Platelet degranulation (R-HSA-114608)

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
Fazirsiran	DM772MW	Alpha-1 antitrypsin deficiency	5C5A	Phase 3	[2]
ARO-AAT	DM2UP6Z	Alopecia	ED70	Phase 2	[1]
Belcesiran	DMLMIGI	Alpha-1 antitrypsin deficiency	5C5A	Phase 2	[3]

References

• [1] Clinical pipeline report, company report or official report of Arrowhead Pharmaceuticals.
• [2] Fazirsiran for Liver Disease Associated with Alpha(1)-Antitrypsin Deficiency. N Engl J Med. 2022 Aug 11;387(6):514-524.
• [3] Clinical pipeline report, company report or official report of Dicerna Pharmaceuticals