Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU3J0ZL)

• DOT Name: Dehydrogenase/reductase SDR family member 11 (DHRS11)
• Synonyms: 17-beta-hydroxysteroid dehydrogenase; 3-beta-hydroxysteroid 3-dehydrogenase; EC 1.1.1.270; Estradiol 17-beta-dehydrogenase; EC 1.1.1.62; Short-chain dehydrogenase/reductase family 24C member 1
• Gene Name: DHRS11
• Related Disease:
  46,XY disorder of sex development
  46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
  Advanced cancer
  Alzheimer disease
  Breast neoplasm
  Castration-resistant prostate carcinoma
  Choriocarcinoma
  Colon adenocarcinoma
  Colorectal carcinoma
  Disorder of sexual differentiation
  Endometrial cancer
  Endometrial carcinoma
  Gastric cancer
  Gastric disease
  Hypospadias
  Multiple sclerosis
  Non-alcoholic fatty liver disease
  Peroxisomal disorder
  Pheochromocytoma
  Polycystic ovarian syndrome
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
  Breast carcinoma
  Hereditary breast ovarian cancer syndrome
  Breast cancer
  Endometriosis
  Invasive ductal breast carcinoma
  Parkinson disease
• UniProt ID: DHR11_HUMAN
• PDB ID: 1XG5
• EC Number: 1.1.1.270; 1.1.1.62
• Pfam ID: PF00106
• Sequence:
  MARPGMERWRDRLALVTGASGGIGAAVARALVQQGLKVVGCARTVGNIEELAAECKSAGY
  PGTLIPYRCDLSNEEDILSMFSAIRSQHSGVDICINNAGLARPDTLLSGSTSGWKDMFNV
  NVLALSICTREAYQSMKERNVDDGHIININSMSGHRVLPLSVTHFYSATKYAVTALTEGL
  RQELREAQTHIRATCISPGVVETQFAFKLHDKDPEKAAATYEQMKCLKPEDVAEAVIYVL
  STPAHIQIGDIQMRPTEQVT
• Function: Catalyzes the conversion of the 17-keto group of estrone, 4- and 5-androstenes and 5-alpha-androstanes into their 17-beta-hydroxyl metabolites and the conversion of the 3-keto group of 3-, 3,17- and 3,20- diketosteroids into their 3-hydroxyl metabolites. Exhibits reductive 3-beta-hydroxysteroid dehydrogenase activity toward 5-beta-androstanes, 5-beta-pregnanes, 4-pregnenes and bile acids. May also reduce endogenous and exogenous alpha-dicarbonyl compounds and xenobiotic alicyclic ketones.
• Tissue Specificity: Isoform 1: Ubiquitously expressed, with highest levels in testis, small intestine, colon, kidney, brain and heart. Isoform 3: Expressed in brain, heart and skeletal muscle.
• KEGG Pathway: Steroid hormone biosynthesis (hsa00140)

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
46,XY disorder of sex development	DIS78CGG	Strong	Genetic Variation	[1]
46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency	DISR1LAL	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[5]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Biomarker	[6]
Choriocarcinoma	DISDBVNL	Strong	Altered Expression	[7]
Colon adenocarcinoma	DISDRE0J	Strong	Altered Expression	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[8]
Disorder of sexual differentiation	DISRMAEZ	Strong	Genetic Variation	[9]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[10]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[10]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[11]
Gastric disease	DISNZNTG	Strong	Altered Expression	[12]
Hypospadias	DIS48CCP	Strong	Genetic Variation	[13]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[14]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[15]
Peroxisomal disorder	DISV185U	Strong	Biomarker	[16]
Pheochromocytoma	DIS56IFV	Strong	Altered Expression	[17]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Altered Expression	[18]
Prostate cancer	DISF190Y	Strong	Biomarker	[19]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[19]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[11]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[3]
Hereditary breast ovarian cancer syndrome	DISWDUGU	moderate	Genetic Variation	[20]
Breast cancer	DIS7DPX1	Limited	Biomarker	[3]
Endometriosis	DISX1AG8	Limited	Genetic Variation	[21]
Invasive ductal breast carcinoma	DIS43J58	Limited	Altered Expression	[22]
Parkinson disease	DISQVHKL	Limited	Altered Expression	[23]

This DOT Affected the Biotransformations of 18 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the oxidation of Estradiol.	[29]
Testosterone	DM7HUNW	Approved	Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the oxidation of Testosterone.	[29]
Menadione	DMSJDTY	Approved	Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the reduction of Menadione.	[29]
Estrone	DM5T6US	Approved	Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the reduction of Estrone.	[29]
Prasterone	DM67VKL	Approved	Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the reduction of Prasterone.	[29]
Dihydrotestosterone	DM3S8XC	Phase 4	Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the oxidation of Dihydrotestosterone.	[29]
Androsterone	DMITJAK	Phase 3	Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the reduction of Androsterone.	[29]
HE2100	DMCP2KH	Discontinued in Phase 1	Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the oxidation of HE2100.	[29]
	DM9CEI5		Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the oxidation of .	[29]
Phenanthrene-9,10-dione	DMG8KS9	Investigative	Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the reduction of Phenanthrene-9,10-dione.	[29]
[3H]estrone-3-sulphate	DMGPF0N	Investigative	Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the reduction of [3H]estrone-3-sulphate.	[29]
4-ANDROSTENE-3-17-DIONE	DMSE8NU	Investigative	Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the reduction of 4-ANDROSTENE-3-17-DIONE.	[29]
1H-Indole-2,3-dione	DMOZ91H	Investigative	Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the reduction of 1H-Indole-2,3-dione.	[29]
1-Phenyl-propane-1,2-dione	DM04SWY	Investigative	Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the reduction of 1-Phenyl-propane-1,2-dione.	[29]
Phenylglyoxal	DMHW93J	Investigative	Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the reduction of Phenylglyoxal.	[29]
ACENAPHTHOQUINONE	DMU3DMH	Investigative	Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the reduction of ACENAPHTHOQUINONE.	[29]
3-keto-lithocholic acid	DM5LUED	Investigative	Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the reduction of 3-keto-lithocholic acid.	[29]
Dehydrocholic acid	DMFK8Y9	Investigative	Dehydrogenase/reductase SDR family member 11 (DHRS11) increases the reduction of Dehydrocholic acid.	[29]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[25]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[26]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[27]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[28]
Quercetin	DM3NC4M	Approved	Quercetin decreases the activity of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[29]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[30]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[31]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[32]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[33]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the activity of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[29]
Sulindac	DM2QHZU	Approved	Sulindac decreases the activity of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[29]
Ketoprofen	DMRKXPT	Approved	Ketoprofen decreases the activity of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[29]
Flufenamic Acid	DMC8VNH	Approved	Flufenamic Acid decreases the activity of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[29]
Fenoprofen	DML5VQ0	Approved	Fenoprofen decreases the activity of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[29]
Suprofen	DMKXJZ7	Approved	Suprofen decreases the activity of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[29]
Flavonoid derivative 1	DMCQP0B	Patented	Flavonoid derivative 1 decreases the activity of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[29]
Zomepirac	DM7APNJ	Withdrawn from market	Zomepirac decreases the activity of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[35]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[32]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[36]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[37]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the activity of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[29]
Kaempferol	DMHEMUB	Investigative	Kaempferol decreases the activity of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[29]
Apigenin	DMI3491	Investigative	Apigenin decreases the activity of Dehydrogenase/reductase SDR family member 11 (DHRS11).	[29]

References

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