Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHF4H9U)

• DOT Name: 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2)
• Synonyms: 11-DH2; 11-beta-HSD2; EC 1.1.1.-; 11-beta-hydroxysteroid dehydrogenase type II; 11-HSD type II; 11-beta-HSD type II; Corticosteroid 11-beta-dehydrogenase isozyme 2; NAD-dependent 11-beta-hydroxysteroid dehydrogenase; Short chain dehydrogenase/reductase family 9C member 3
• Gene Name: HSD11B2
• Related Disease: Apparent mineralocorticoid excess
• UniProt ID: DHI2_HUMAN
• EC Number: 1.1.1.-
• Pfam ID: PF00106
• Sequence:
  MERWPWPSGGAWLLVAARALLQLLRSDLRLGRPLLAALALLAALDWLCQRLLPPPAALAV
  LAAAGWIALSRLARPQRLPVATRAVLITGCDSGFGKETAKKLDSMGFTVLATVLELNSPG
  AIELRTCCSPRLRLLQMDLTKPGDISRVLEFTKAHTTSTGLWGLVNNAGHNEVVADAELS
  PVATFRSCMEVNFFGALELTKGLLPLLRSSRGRIVTVGSPAGDMPYPCLGAYGTSKAAVA
  LLMDTFSCELLPWGVKVSIIQPGCFKTESVRNVGQWEKRKQLLLANLPQELLQAYGKDYI
  EHLHGQFLHSLRLAMSDLTPVVDAITDALLAARPRRRYYPGQGLGLMYFIHYYLPEGLRR
  RFLQAFFISHCLPRALQPGQPGTTPPQDAAQDPNLSPGPSPAVAR
• Function: Catalyzes the conversion of biologically active 11beta-hydroxyglucocorticoids (11beta-hydroxysteroid) such as cortisol, to inactive 11-ketoglucocorticoids (11-oxosteroid) such as cortisone, in the presence of NAD(+). Functions as a dehydrogenase (oxidase), thereby decreasing the concentration of active glucocorticoids, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids. Plays an important role in maintaining glucocorticoids balance during preimplantation and protects the fetus from excessive maternal corticosterone exposure. Catalyzes the oxidation of 11beta-hydroxytestosterone (11beta,17beta-dihydroxyandrost-4-ene-3-one) to 11-ketotestosterone (17beta-hydroxyandrost-4-ene-3,11-dione), a major bioactive androgen. Catalyzes the conversion of 11beta-hydroxyandrostenedione (11beta-hydroxyandrost-4-ene-3,17-dione) to 11-ketoandrostenedione (androst-4-ene-3,11,17-trione), which can be further metabolized to 11-ketotestosterone. Converts 7-beta-25-dihydroxycholesterol to 7-oxo-25-hydroxycholesterol in vitro. 7-beta-25-dihydroxycholesterol (not 7-oxo-25-hydroxycholesterol) acts as a ligand for the G-protein-coupled receptor (GPCR) Epstein-Barr virus-induced gene 2 (EBI2) and may thereby regulate immune cell migration. May protect ovulating oocytes and fertilizing spermatozoa from the adverse effects of cortisol.
• Tissue Specificity: Expressed in kidney, placenta, pancreas, prostate, ovary, small intestine and colon, and in lower levels in the spleen and testis . At midgestation, expressed at high levels in placenta and in fetal kidney and, at much lower levels, in fetal lung and testis .
• KEGG Pathway:
  Steroid hormone biosynthesis (hsa00140)
  Metabolic pathways (hsa01100)
  Aldosterone-regulated sodium reabsorption (hsa04960)
• Reactome Pathway:
  Prednisone ADME (R-HSA-9757110)
  Glucocorticoid biosynthesis (R-HSA-194002)
• BioCyc Pathway: MetaCyc:ENSG00000176387-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Apparent mineralocorticoid excess	DISRJBUV	Strong	Autosomal recessive	[1]

This DOT Affected the Regulation of Drug Effects of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Prednisolone	DMQ8FR2	Approved	11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) increases the metabolism of Prednisolone.	[37]
Betamethasone	DMAHJEF	Approved	11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) increases the metabolism of Betamethasone.	[37]
Beclomethasone dipropionate	DM5NW1E	Phase 4	11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) increases the metabolism of Beclomethasone dipropionate.	[37]

This DOT Affected the Biotransformations of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cortisone	DMU5QZX	Approved	11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) increases the chemical synthesis of Cortisone.	[24]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	Investigative	11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) increases the reduction of Nicotinamide-Adenine-Dinucleotide.	[38]

53 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[10]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[12]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[13]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[14]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[15]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[16]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[17]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[11]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone decreases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[18]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[13]
Dinoprostone	DMTYOPD	Approved	Dinoprostone decreases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[17]
Masoprocol	DMMVNZ0	Approved	Masoprocol increases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[11]
Danazol	DML8KTN	Approved	Danazol decreases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[19]
Procainamide	DMNMXR8	Approved	Procainamide increases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[9]
Itraconazole	DMCR1MV	Approved	Itraconazole decreases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[20]
Metyrapone	DMI7FVQ	Approved	Metyrapone decreases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[21]
Zileuton	DMVRIC2	Approved	Zileuton increases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[17]
Oxymetholone	DMFXUT8	Approved	Oxymetholone decreases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[19]
Posaconazole	DMUL5EW	Approved	Posaconazole decreases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[20]
Fluoxymesterone	DMUHCF1	Approved	Fluoxymesterone decreases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[19]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[23]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[6]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram decreases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[24]
BAICALEIN	DM4C7E6	Phase 2	BAICALEIN increases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[11]
LTB4	DME26RS	Phase 2	LTB4 decreases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[25]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[26]
PGF2alpha	DM4XAU7	Clinical trial	PGF2alpha decreases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[27]
AA-861	DMPEB0Z	Terminated	AA-861 increases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[28]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[29]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[30]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[13]
U0126	DM31OGF	Investigative	U0126 increases the expression of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[31]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate decreases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[32]
NSC-1771	DMNXDGQ	Investigative	NSC-1771 decreases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[33]
N-nonylphenol	DMH3OUX	Investigative	N-nonylphenol decreases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[34]
Pyrrolidine dithiocarbamate	DM5ZAS6	Investigative	Pyrrolidine dithiocarbamate decreases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[24]
1,4-Dithiothreitol	DMIFOXE	Investigative	1,4-Dithiothreitol increases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[35]
HPTE	DMRPZD4	Investigative	HPTE decreases the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2).	[36]

References

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