Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRE1M1T)

• DOT Name: Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB)
• Synonyms: EC 1.3.5.1; Iron-sulfur subunit of complex II; Ip
• Gene Name: SDHB
• Related Disease:
  Carney-Stratakis syndrome
  Gastrointestinal stromal tumour
  Hereditary pheochromocytoma-paraganglioma
  Mitochondrial disease
  Paragangliomas 4
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Cardiomyopathy
  Chromosomal disorder
  Chronic obstructive pulmonary disease
  Coffin-Siris syndrome
  Colorectal carcinoma
  Diabetic retinopathy
  Dilated cardiomyopathy 1A
  Exanthem
  Hereditary leiomyomatosis and renal cell cancer
  Hereditary neoplastic syndrome
  High blood pressure
  Kidney cancer
  Kidney neoplasm
  Leiomyoma
  Leukodystrophy
  Mitochondrial complex 2 deficiency, nuclear type 4
  Multiple endocrine neoplasia
  Multiple endocrine neoplasia type 1
  Multiple endocrine neoplasia type 2
  Multiple endocrine neoplasia type 2A
  Neurofibromatosis type 1
  Precancerous condition
  Renal cell carcinoma
  Skin cancer
  Subarachnoid hemorrhage
  Thyroid cancer
  Thyroid tumor
  Urinary bladder cancer
  Urinary bladder neoplasm
  Uterine fibroids
  Dementia
  Hepatocellular carcinoma
  Small lymphocytic lymphoma
  Cowden disease
  Obsolete mitochondrial complex II deficiency
  Thyroid gland carcinoma
  Adenocarcinoma
  Corpus callosum, agenesis of
  Gastric cancer
  Neuroendocrine neoplasm
  Renal carcinoma
  Thyroid gland papillary carcinoma
• UniProt ID: SDHB_HUMAN
• PDB ID: 7KCL; 7KCM; 7KLU; 7KLV; 8GS8
• EC Number: 1.3.5.1
• Pfam ID: PF13085 ; PF13534
• Sequence:
  MAAVVALSLRRRLPATTLGGACLQASRGAQTAAATAPRIKKFAIYRWDPDKAGDKPHMQT
  YEVDLNKCGPMVLDALIKIKNEVDSTLTFRRSCREGICGSCAMNINGGNTLACTRRIDTN
  LNKVSKIYPLPHMYVIKDLVPDLSNFYAQYKSIEPYLKKKDESQEGKQQYLQSIEEREKL
  DGLYECILCACCSTSCPSYWWNGDKYLGPAVLMQAYRWMIDSRDDFTEERLAKLQDPFSL
  YRCHTIMNCTRTCPKGLNPGKAIAEIKKMMATYKEKKASV
• Function: Iron-sulfur protein (IP) subunit of the succinate dehydrogenase complex (mitochondrial respiratory chain complex II), responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
• KEGG Pathway:
  Citrate cycle (TCA cycle) (hsa00020)
  Oxidative phosphorylation (hsa00190)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Thermogenesis (hsa04714)
  Non-alcoholic fatty liver disease (hsa04932)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Citric acid cycle (TCA cycle) (R-HSA-71403)
  Respiratory electron transport (R-HSA-611105)
• BioCyc Pathway: MetaCyc:ENSG00000117118-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carney-Stratakis syndrome	DISP3P3F	Definitive	Mitochondrial	[1]
Gastrointestinal stromal tumour	DIS6TJYS	Definitive	Autosomal dominant	[2]
Hereditary pheochromocytoma-paraganglioma	DISP9K7L	Definitive	Autosomal dominant	[3]
Mitochondrial disease	DISKAHA3	Definitive	Autosomal recessive	[3]
Paragangliomas 4	DISTCBTV	Definitive	Autosomal dominant	[4]
Bladder cancer	DISUHNM0	Strong	Genetic Variation	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[7]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[8]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Altered Expression	[9]
Coffin-Siris syndrome	DIS8L03H	Strong	Biomarker	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[11]
Diabetic retinopathy	DISHGUJM	Strong	Genetic Variation	[12]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Altered Expression	[13]
Exanthem	DISAFOQN	Strong	Genetic Variation	[14]
Hereditary leiomyomatosis and renal cell cancer	DISN22G2	Strong	Biomarker	[15]
Hereditary neoplastic syndrome	DISGXLG5	Strong	CausalMutation	[16]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[17]
Kidney cancer	DISBIPKM	Strong	Biomarker	[18]
Kidney neoplasm	DISBNZTN	Strong	Biomarker	[19]
Leiomyoma	DISLDDFN	Strong	Genetic Variation	[20]
Leukodystrophy	DISVY1TT	Strong	Genetic Variation	[21]
Mitochondrial complex 2 deficiency, nuclear type 4	DISGOCEA	Strong	Autosomal recessive	[7]
Multiple endocrine neoplasia	DISZGBKW	Strong	Biomarker	[22]
Multiple endocrine neoplasia type 1	DIS0RJRK	Strong	Genetic Variation	[23]
Multiple endocrine neoplasia type 2	DISPQ4Y5	Strong	Altered Expression	[24]
Multiple endocrine neoplasia type 2A	DIS7D3W2	Strong	Altered Expression	[24]
Neurofibromatosis type 1	DIS53JH9	Strong	Biomarker	[25]
Precancerous condition	DISV06FL	Strong	Altered Expression	[26]
Renal cell carcinoma	DISQZ2X8	Strong	Autosomal dominant	[27]
Skin cancer	DISTM18U	Strong	Biomarker	[28]
Subarachnoid hemorrhage	DISI7I8Y	Strong	Biomarker	[29]
Thyroid cancer	DIS3VLDH	Strong	Genetic Variation	[30]
Thyroid tumor	DISLVKMD	Strong	Genetic Variation	[31]
Urinary bladder cancer	DISDV4T7	Strong	Genetic Variation	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Genetic Variation	[5]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[20]
Dementia	DISXL1WY	moderate	Biomarker	[32]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[33]
Small lymphocytic lymphoma	DIS30POX	moderate	Genetic Variation	[34]
Cowden disease	DISMYKCE	Supportive	Autosomal dominant	[35]
Obsolete mitochondrial complex II deficiency	DIS67XU0	Supportive	Autosomal recessive	[7]
Thyroid gland carcinoma	DISMNGZ0	Disputed	Genetic Variation	[30]
Adenocarcinoma	DIS3IHTY	Limited	Genetic Variation	[36]
Corpus callosum, agenesis of	DISO9P40	Limited	Altered Expression	[37]
Gastric cancer	DISXGOUK	Limited	Posttranslational Modification	[36]
Neuroendocrine neoplasm	DISNPLOO	Limited	Genetic Variation	[38]
Renal carcinoma	DISER9XT	Limited	Biomarker	[18]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Olaparib	DM8QB1D	Approved	Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB) increases the response to substance of Olaparib.	[15]
Talazoparib	DM1KS78	Approved	Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB) increases the response to substance of Talazoparib.	[15]

16 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 Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[40]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[41]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[42]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[43]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[44]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[46]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[47]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[48]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[49]
Zidovudine	DM4KI7O	Approved	Zidovudine decreases the expression of Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[50]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[51]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[52]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[53]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[55]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[56]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[57]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB).	[54]

References

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