Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFHWIY8)

• DOT Name: Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2)
• Synonyms: EC 1.1.1.-; Dicarbonyl reductase HEP27; Protein D; Short chain dehydrogenase/reductase family 25C member 1; Protein SDR25C1
• Gene Name: DHRS2
• Related Disease:
  Acute otitis media
  Advanced cancer
  Breast cancer
  Colorectal carcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Influenza
  Kidney cancer
  Ovarian cancer
  Ovarian neoplasm
  Renal carcinoma
  Otitis media
  Chronic obstructive pulmonary disease
  Nasopharyngeal carcinoma
• UniProt ID: DHRS2_HUMAN
• EC Number: 1.1.1.-
• Pfam ID: PF13561
• Sequence:
  MLSAVARGYQGWFHPCARLSVRMSSTGIDRKGVLANRVAVVTGSTSGIGFAIARRLARDG
  AHVVISSRKQQNVDRAMAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVDFLVCS
  AGVNPLVGSTLGTSEQIWDKILSVNVKSPALLLSQLLPYMENRRGAVILVSSIAAYNPVV
  ALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDFSKVFHGNESLWKNFKEHH
  QLQRIGESEDCAGIVSFLCSPDASYVNGENIAVAGYSTRL
• Function: NADPH-dependent oxidoreductase which catalyzes the reduction of dicarbonyl compounds. Displays reductase activity in vitro with 3,4-hexanedione, 2,3-heptanedione and 1-phenyl-1,2-propanedione as substrates. May function as a dicarbonyl reductase in the enzymatic inactivation of reactive carbonyls involved in covalent modification of cellular components. Also displays a minor hydroxysteroid dehydrogenase activity toward bile acids such as ursodeoxycholic acid (UDCA) and isoursodeoxycholic acid (isoUDCA), which makes it unlikely to control hormone levels. Doesn't show any activity in vitro with retinoids and sugars as substrates. Attenuates MDM2-mediated p53/TP53 degradation, leading to p53/TP53 stabilization and increased transcription activity, resulting in the accumulation of MDM2 and CDKN1A/p21. Reduces proliferation, migration and invasion of cancer cells and well as the production of ROS in cancer.
• Tissue Specificity: Widely expressed, with highest levels in liver and kidney, followed by heart, spleen, skeletal muscle and placenta. In hemopoietic cells, expressed in dendritic cells, but not in monocytes, macrophages, granulocytes, nor in B and T lymphocytes.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute otitis media	DISL8D8G	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[5]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[2]
Influenza	DIS3PNU3	Strong	Biomarker	[6]
Kidney cancer	DISBIPKM	Strong	Biomarker	[7]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[5]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[5]
Renal carcinoma	DISER9XT	Strong	Biomarker	[7]
Otitis media	DISGZDUO	moderate	Biomarker	[6]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Biomarker	[8]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[9]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2) affects the response to substance of Methotrexate.	[34]
Mitoxantrone	DMM39BF	Approved	Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2) affects the response to substance of Mitoxantrone.	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[15]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[16]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[17]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[18]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[19]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[20]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[20]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[21]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[23]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[16]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[24]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[25]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[26]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[28]
Mivebresib	DMCPF90	Phase 1	Mivebresib increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[25]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[21]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[30]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[31]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[32]
(E)-4-(3,5-dimethoxystyryl)phenol	DMYXI2V	Investigative	(E)-4-(3,5-dimethoxystyryl)phenol increases the expression of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2).	[29]

References

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