Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1LQSGX)

• DOT Name: Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2)
• Gene Name: MTHFD2
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Coronary heart disease
  Acute myelogenous leukaemia
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Classic Hodgkin lymphoma
  Clear cell renal carcinoma
  Colorectal carcinoma
  Glioma
  Hepatocellular carcinoma
  Liver cancer
  Non-small-cell lung cancer
  Renal cell carcinoma
  leukaemia
  Leukemia
  Neoplasm
• UniProt ID: MTDC_HUMAN
• PDB ID: 5TC4; 6JIB; 6JID; 6KG2; 6S4A; 6S4E; 6S4F; 7EHJ; 7EHM; 7EHN; 7EHV
• EC Number: 1.5.1.15; 3.5.4.9
• Pfam ID: PF00763 ; PF02882
• Sequence:
  MAATSLMSALAARLLQPAHSCSLRLRPFHLAAVRNEAVVISGRKLAQQIKQEVRQEVEEW
  VASGNKRPHLSVILVGENPASHSYVLNKTRAAAVVGINSETIMKPASISEEELLNLINKL
  NNDDNVDGLLVQLPLPEHIDERRICNAVSPDKDVDGFHVINVGRMCLDQYSMLPATPWGV
  WEIIKRTGIPTLGKNVVVAGRSKNVGMPIAMLLHTDGAHERPGGDATVTISHRYTPKEQL
  KKHTILADIVISAAGIPNLITADMIKEGAAVIDVGINRVHDPVTAKPKLVGDVDFEGVRQ
  KAGYITPVPGGVGPMTVAMLMKNTIIAAKKVLRLEEREVLKSKELGVATN
• Function: Although its dehydrogenase activity is NAD-specific, it can also utilize NADP at a reduced efficiency.
• KEGG Pathway:
  One carbon pool by folate (hsa00670)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Metabolism of folate and pterines (R-HSA-196757)
• BioCyc Pathway: MetaCyc:HS00858-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Definitive	Biomarker	[1]
Atherosclerosis	DISMN9J3	Definitive	Biomarker	[1]
Coronary heart disease	DIS5OIP1	Definitive	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[5]
Clear cell renal carcinoma	DISBXRFJ	Strong	Posttranslational Modification	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Glioma	DIS5RPEH	Strong	Biomarker	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[9]
Liver cancer	DISDE4BI	Strong	Biomarker	[10]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[11]
Renal cell carcinoma	DISQZ2X8	Strong	Posttranslational Modification	[6]
leukaemia	DISS7D1V	moderate	Biomarker	[12]
Leukemia	DISNAKFL	moderate	Biomarker	[12]
Neoplasm	DISZKGEW	moderate	Altered Expression	[2]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2) affects the response to substance of Mitoxantrone.	[42]
Artesunate	DMR27C8	Approved	Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2) decreases the response to substance of Artesunate.	[43]
Pemetrexed	DMMX2E6	Approved	Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2) increases the response to substance of Pemetrexed.	[5]

32 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 Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[16]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[18]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[20]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[21]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[22]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[23]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[24]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[25]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[26]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[24]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[27]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[22]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[28]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[22]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[29]
Bexarotene	DMOBIKY	Approved	Bexarotene decreases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[30]
Fenretinide	DMRD5SP	Phase 3	Fenretinide affects the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[31]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[22]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[34]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[36]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[38]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[39]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[40]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2).	[37]

References

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