Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTVG0SN)

• DTT Name: S-nitrosoglutathione reductase (CBR1)
• Synonyms: ProstaglandinE(2) 9reductase; Prostaglandin 9ketoreductase; NADPHdependent carbonyl reductase 1; Carbonyl reductase [NADPH] 1; CBR1; 15hydroxyprostaglandin dehydrogenase [NADP(+)]
• Gene Name: CBR1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Short-chain dehydrogenases reductase
• UniProt ID: CBR1_HUMAN
• TTD ID: T70518
• EC Number: EC 1.1.1.184
• Sequence:
  MSSGIHVALVTGGNKGIGLAIVRDLCRLFSGDVVLTARDVTRGQAAVQQLQAEGLSPRFH
  QLDIDDLQSIRALRDFLRKEYGGLDVLVNNAGIAFKVADPTPFHIQAEVTMKTNFFGTRD
  VCTELLPLIKPQGRVVNVSSIMSVRALKSCSPELQQKFRSETITEEELVGLMNKFVEDTK
  KGVHQKEGWPSSAYGVTKIGVTVLSRIHARKLSEQRKGDKILLNACCPGWVRTDMAGPKA
  TKSPEEGAETPVYLALLPPDAEGPHGQFVSEKRVEQW
• Function: NADPH-dependent reductase with broad substratespecificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol. Can convert prostaglandin E2 to prostaglandin F2-alpha. Can bind glutathione, which explains its higher affinity for glutathione-conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione.
• KEGG Pathway:
  Arachidonic acid metabolism (hsa00590)
  Folate biosynthesis (hsa00790)
  Metabolism of xenobiotics by cytochrome P450 (hsa00980)
  Metabolic pathways (hsa01100)
  Chemical carcinogenesis - DNA adducts (hsa05204)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
• Reactome Pathway: Synthesis of Prostaglandins (PG) and Thromboxanes (TX) (R-HSA-2162123)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
N6022	DMN7EUO	Asthma	CA23	Phase 2	[1]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Asthma	CA23	Nasal and bronchial airway	1.94E-06	0.71	0.77

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

• DTT DME Name: NADPH-dependent carbonyl reductase 1 (CBR1) DME Info
• Gene Name: CBR1

3 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Daunorubicin	DMQUSBT	Acute monocytic leukemia		Approved	[2]
FENOFIBRIC ACID	DMGO2MC	Cardiovascular disease	BA00-BE2Z	Approved	[3]
Menadione	DMSJDTY	Vitamin K deficiency	5B59	Approved	[4]

1 Clinical Trial Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PGF2alpha	DM4XAU7	Solid tumour/cancer	2A00-2F9Z	Clinical trial	[5]

1 Preclinical Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VUFB-11502	DM7WFR0	N. A.	N. A.	Preclinical	[6]

2 Investigative Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BRN-3548355	DM4KXT0	N. A.	N. A.	Investigative	[7]
Phenanthrene-9,10-dione	DMG8KS9	Discovery agent	N.A.	Investigative	[8]

References

• [1] Mechanism of inhibition for N6022, a first-in-class drug targeting S-nitrosoglutathione reductase. Biochemistry. 2012 Mar 13;51(10):2157-68.
• [2] Flavonoids as inhibitors of human carbonyl reductase 1. Chem Biol Interact. 2008 Jul 30;174(2):98-108.
• [3] In vitro metabolism of fenofibric acid by carbonyl reducing enzymes. Chem Biol Interact. 2016 Oct 25;258:153-8.
• [4] Polycyclic aromatic hydrocarbon quinones and glutathione thioethers as substrates and inhibitors of the human placental NADP-linked 15-hydroxyprostaglandin dehydrogenase. J Biol Chem. 1987 Sep 15;262(26):12448-51.
• [5] Metabolism of prostaglandins by the nonpregnant human uterus. J Clin Endocrinol Metab. 1983 Apr;56(4):678-85.
• [6] The critical role of oxidative stress in the toxicity and metabolism of quinoxaline 1,4-di-N-oxides in vitro and in vivo. Drug Metab Rev. 2016 May;48(2):159-82.
• [7] Characterization of enzymes participating in carbonyl reduction of 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) in human placenta. Chem Biol Interact. 2001 Jan 30;130-132(1-3):737-48.
• [8] Studies on reduction of S-nitrosoglutathione by human carbonyl reductases 1 and 3. Chem Biol Interact. 2011 May 30;191(1-3):95-103.