Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV01EFP)

• DOT Name: Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L)
• Synonyms: EC 6.3.4.3; Formyltetrahydrofolate synthetase
• Gene Name: MTHFD1L
• Related Disease:
  Acute coronary syndrome
  Advanced cancer
  Carcinoma of esophagus
  Colorectal carcinoma
  Coronary heart disease
  Depression
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Megaloblastic anemia
  Neoplasm
  Neoplasm of esophagus
  Neural tube defect
  Peripheral arterial disease
  Severe combined immunodeficiency
  Hepatocellular carcinoma
  Bladder cancer
  Myocardial infarction
  Schizophrenia
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: C1TM_HUMAN
• EC Number: 6.3.4.3
• Pfam ID: PF01268 ; PF00763 ; PF02882
• Sequence:
  MGTRLPLVLRQLRRPPQPPGPPRRLRVPCRASSGGGGGGGGGREGLLGQRRPQDGQARSS
  CSPGGRTPAARDSIVREVIQNSKEVLSLLQEKNPAFKPVLAIIQAGDDNLMQEINQNLAE
  EAGLNITHICLPPDSSEAEIIDEILKINEDTRVHGLALQISENLFSNKVLNALKPEKDVD
  GVTDINLGKLVRGDAHECFVSPVAKAVIELLEKSGVNLDGKKILVVGAHGSLEAALQCLF
  QRKGSMTMSIQWKTRQLQSKLHEADIVVLGSPKPEEIPLTWIQPGTTVLNCSHDFLSGKV
  GCGSPRIHFGGLIEEDDVILLAAALRIQNMVSSGRRWLREQQHRRWRLHCLKLQPLSPVP
  SDIEISRGQTPKAVDVLAKEIGLLADEIEIYGKSKAKVRLSVLERLKDQADGKYVLVAGI
  TPTPLGEGKSTVTIGLVQALTAHLNVNSFACLRQPSQGPTFGVKGGAAGGGYAQVIPMEE
  FNLHLTGDIHAITAANNLLAAAIDTRILHENTQTDKALYNRLVPLVNGVREFSEIQLARL
  KKLGINKTDPSTLTEEEVSKFARLDIDPSTITWQRVLDTNDRFLRKITIGQGNTEKGHYR
  QAQFDIAVASEIMAVLALTDSLADMKARLGRMVVASDKSGQPVTADDLGVTGALTVLMKD
  AIKPNLMQTLEGTPVFVHAGPFANIAHGNSSVLADKIALKLVGEEGFVVTEAGFGADIGM
  EKFFNIKCRASGLVPNVVVLVATVRALKMHGGGPSVTAGVPLKKEYTEENIQLVADGCCN
  LQKQIQITQLFGVPVVVALNVFKTDTRAEIDLVCELAKRAGAFDAVPCYHWSVGGKGSVD
  LARAVREAASKRSRFQFLYDVQVPIVDKIRTIAQAVYGAKDIELSPEAQAKIDRYTQQGF
  GNLPICMAKTHLSLSHQPDKKGVPRDFILPISDVRASIGAGFIYPLVGTMSTMPGLPTRP
  CFYDIDLDTETEQVKGLF
• Function: May provide the missing metabolic reaction required to link the mitochondria and the cytoplasm in the mammalian model of one-carbon folate metabolism complementing thus the enzymatic activities of MTHFD2.
• Tissue Specificity: Detected in most tissues, highest expression found in placenta, thymus and brain. Low expression is found in liver and skeletal muscle. Up-regulated in colon adenocarcinoma.
• 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)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute coronary syndrome	DIS7DYEW	Strong	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[5]
Depression	DIS3XJ69	Strong	Genetic Variation	[6]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[3]
Megaloblastic anemia	DISVIZPC	Strong	Genetic Variation	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[3]
Neural tube defect	DIS5J95E	Strong	Biomarker	[8]
Peripheral arterial disease	DIS78WFB	Strong	Genetic Variation	[9]
Severe combined immunodeficiency	DIS6MF4Q	Strong	Genetic Variation	[7]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[10]
Bladder cancer	DISUHNM0	Limited	Altered Expression	[11]
Myocardial infarction	DIS655KI	Limited	Genetic Variation	[12]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[13]
Urinary bladder cancer	DISDV4T7	Limited	Altered Expression	[11]
Urinary bladder neoplasm	DIS7HACE	Limited	Altered Expression	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[14]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[22]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[19]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[20]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[21]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[23]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[24]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[25]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[26]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[27]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[28]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[29]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[24]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[31]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[32]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[36]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L).	[37]

References

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