Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT9LX82)

• DTT Name: Serum paraoxonase/arylesterase 1 (PON1)
• Synonyms: Serum paraoxonase; Serum aryldialkylphosphatase 1; Serum aryldiakylphosphatase 1; PON 1; PON; K-45; Aromatic esterase 1; A-esterase 1
• Gene Name: PON1
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Carboxylic ester hydrolase
• UniProt ID: PON1_HUMAN
• TTD ID: T34562
• EC Number: EC 3.1.1.2
• Sequence:
  MAKLIALTLLGMGLALFRNHQSSYQTRLNALREVQPVELPNCNLVKGIETGSEDLEILPN
  GLAFISSGLKYPGIKSFNPNSPGKILLMDLNEEDPTVLELGITGSKFDVSSFNPHGISTF
  TDEDNAMYLLVVNHPDAKSTVELFKFQEEEKSLLHLKTIRHKLLPNLNDIVAVGPEHFYG
  TNDHYFLDPYLQSWEMYLGLAWSYVVYYSPSEVRVVAEGFDFANGINISPDGKYVYIAEL
  LAHKIHVYEKHANWTLTPLKSLDFNTLVDNISVDPETGDLWVGCHPNGMKIFFYDSENPP
  ASEVLRIQNILTEEPKVTQVYAENGTVLQGSTVASVYKGKLLIGTVFHKALYCEL
• Function: Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic acid esters. Mediates an enzymatic protection of low density lipoproteins against oxidative modification and the consequent series of events leading to atheroma formation. Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides.
• Reactome Pathway:
  Atorvastatin ADME (R-HSA-9754706)
  Synthesis of 5-eicosatetraenoic acids (R-HSA-2142688)

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Serum paraoxonase/arylesterase 1 (PON1) DME Info
• Gene Name: PON1

2 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Loteprednol Etabonate	DM8QTJI	Eye inflammation	9A02	Approved	[2]
Prulifloxacin	DMOK965	Urinary tract infection	GC08	Approved	[3]

1 Clinical Trial Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RTR-003632	DM45NHF	N. A.	N. A.	Phase 2	[4]

6 Investigative Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Coumaranone	DM7TCPG	N. A.	N. A.	Investigative	[4]
Dihydrocoumarin	DMGLX1R	N. A.	N. A.	Investigative	[4]
gamma-butyrolactone	DMDCZWY	Discovery agent	N.A.	Investigative	[4]
Gamma-thiobutyrolactone	DM83HUI	N. A.	N. A.	Investigative	[4]
Homogentisic acid	DMQD0YW	N. A.	N. A.	Investigative	[4]
PARAOXON	DMN4ZKC	Discovery agent	N.A.	Investigative	[4]

References

• [1] Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice. Circulation. 2002 Jul 23;106(4):484-90.
• [2] Identification of esterase involved in the metabolism of two corticosteroid soft drugs. Biochem Pharmacol. 2017 Mar 1;127:82-89.
• [3] Paraoxonases-1, -2 and -3: what are their functions? Chem Biol Interact. 2016 Nov 25;259(Pt B):51-62.
• [4] Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters. Drug Metab Dispos. 2000 Nov;28(11):1335-42.