Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT62RL5P)

• DOT Name: D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1)
• Synonyms: EC 1.1.1.30; 3-hydroxybutyrate dehydrogenase; BDH; Short chain dehydrogenase/reductase family 9C member 1
• Gene Name: BDH1
• Related Disease:
  Advanced cancer
  Glioma
  Hyperthyroidism
  Cardiac failure
  Congestive heart failure
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1A
  Myelodysplastic syndrome
  Breast cancer
  Breast carcinoma
  Neoplasm
  Hepatitis
• UniProt ID: BDH_HUMAN
• EC Number: 1.1.1.30
• Pfam ID: PF00106
• Sequence:
  MLATRLSRPLSRLPGKTLSACDRENGARRPLLLGSTSFIPIGRRTYASAAEPVGSKAVLV
  TGCDSGFGFSLAKHLHSKGFLVFAGCLMKDKGHDGVKELDSLNSDRLRTVQLNVCSSEEV
  EKVVEIVRSSLKDPEKGMWGLVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFL
  PLIRRAKGRVVNISSMLGRMANPARSPYCITKFGVEAFSDCLRYEMYPLGVKVSVVEPGN
  FIAATSLYSPESIQAIAKKMWEELPEVVRKDYGKKYFDEKIAKMETYCSSGSTDTSPVID
  AVTHALTATTPYTRYHPMDYYWWLRMQIMTHLPGAISDMIYIR
• KEGG Pathway:
  Butanoate metabolism (hsa00650)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Synthesis of Ketone Bodies (R-HSA-77111)
  Utilization of Ketone Bodies (R-HSA-77108)
• BioCyc Pathway: MetaCyc:HS08579-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Altered Expression	[1]
Glioma	DIS5RPEH	Definitive	Altered Expression	[2]
Hyperthyroidism	DISX87ZH	Definitive	Biomarker	[3]
Cardiac failure	DISDC067	Strong	Biomarker	[4]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[4]
Dilated cardiomyopathy	DISX608J	Strong	Biomarker	[4]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[4]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[6]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[6]
Neoplasm	DISZKGEW	moderate	Altered Expression	[6]
Hepatitis	DISXXX35	Limited	Altered Expression	[7]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cyclophosphamide	DM4O2Z7	Approved	D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1) affects the response to substance of Cyclophosphamide.	[31]

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 D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[25]

22 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 D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[12]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[13]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[15]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[16]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[17]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[18]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[19]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[20]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[21]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[23]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[26]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[28]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[29]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1).	[30]

References

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• [21] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [22] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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• [24] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
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