Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Vitamin K-dependent protein C (PROC)
• Synonyms: Vitamin K-dependent protein C light chain; Vitamin K-dependent protein C heavy chain; PROC; Blood coagulation factor XIV; Autoprothrombin IIA; Anticoagulant protein C; Activation peptide
• Gene Name: PROC
• DTT Type: Successful target; [1]
• BioChemical Class: Peptidase
• UniProt ID: PROC_HUMAN
• TTD ID: T24836
• EC Number: EC 3.4.21.69
• Sequence:
  MWQLTSLLLFVATWGISGTPAPLDSVFSSSERAHQVLRIRKRANSFLEELRHSSLERECI
  EEICDFEEAKEIFQNVDDTLAFWSKHVDGDQCLVLPLEHPCASLCCGHGTCIDGIGSFSC
  DCRSGWEGRFCQREVSFLNCSLDNGGCTHYCLEEVGWRRCSCAPGYKLGDDLLQCHPAVK
  FPCGRPWKRMEKKRSHLKRDTEDQEDQVDPRLIDGKMTRRGDSPWQVVLLDSKKKLACGA
  VLIHPSWVLTAAHCMDESKKLLVRLGEYDLRRWEKWELDLDIKEVFVHPNYSKSTTDNDI
  ALLHLAQPATLSQTIVPICLPDSGLAERELNQAGQETLVTGWGYHSSREKEAKRNRTFVL
  NFIKIPVVPHNECSEVMSNMVSENMLCAGILGDRQDACEGDSGGPMVASFHGTWFLVGLV
  SWGEGCGLLHNYGVYTKVSRYLDWIHGHIRDKEAPQKSWAP
• Function: Protein C is avitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids.
• KEGG Pathway: Complement and coagulation cascades (hsa04610)
• Reactome Pathway:
  Common Pathway of Fibrin Clot Formation (R-HSA-140875)
  Gamma-carboxylation of protein precursors (R-HSA-159740)
  Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus (R-HSA-159763)
  Removal of aminoterminal propeptides from gamma-carboxylated proteins (R-HSA-159782)
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Intrinsic Pathway of Fibrin Clot Formation (R-HSA-140837)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sodium Tetradecyl Sulfate	DM4QFXJ	Hemangioma	2E81-2F2Y	Approved	[1]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ancrod	DMK2Y4V	Blood forming organ disorder	JB64.1	Phase 3	[2]
3K3A-APC	DMTLR6Y	Cerebrovascular ischaemia	8B1Z	Phase 2	[3]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GED-aPC	DM041IZ	Cardiovascular disease	BA00-BE2Z	Discontinued in Phase 1	[4]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID24418773C37	DMG4NQV	Discovery agent	N.A.	Investigative	[5]
RPR-118071	DM61VHF	Discovery agent	N.A.	Investigative	[6]
RPR-120844	DM1V0MD	Discovery agent	N.A.	Investigative	[6]

References

• [1] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
• [2] Ancrod (Arvin) as an alternative to heparin anticoagulation for cardiopulmonary bypass. Anesthesiology. 1989 Dec;71(6):870-7.
• [3] Preclinical safety and pharmacokinetic profile of 3K3A-APC, a novel, modified activated protein C for ischemic stroke. Curr Pharm Des. 2012;18(27):4215-22.
• [4] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2396).
• [5] Design, synthesis, and SAR of a series of activated protein C (APC) inhibitors with selectivity against thrombin for the treatment of haemophilia. Bioorg Med Chem Lett. 2014 Feb 1;24(3):821-7.
• [6] Design and structure-activity relationships of potent and selective inhibitors of blood coagulation factor Xa. J Med Chem. 1999 Sep 9;42(18):3557-71.