Details of Drug Off-Target (DOT)

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

• DOT Name: Sodium-dependent glucose transporter 1 (MFSD4B)
• Synonyms: Major facilitator superfamily domain-containing protein 4B
• Gene Name: MFSD4B
• Related Disease:
  Colorectal carcinoma
  Type-1 diabetes
  Psoriasis
  Psoriatic arthritis
  Rheumatoid arthritis
• UniProt ID: MFS4B_HUMAN
• Pfam ID: PF07690
• Sequence:
  MLCASFLGLGLSVAIVGPTFQDLATNVNRNISSLSFIFVGRALGYLSGSVIGGFLVDVMN
  YFLLLGISMSATTVGLYLVPFCKTAILLTVMMSIFGVSIGILDTGGNVLILAIWGDKGAP
  HMQALHFSFALGAFLAPLLAKLALGPTASAENHTESDFHPALNQSSDADSEALFGVPNDK
  NLLWAYAVIGTYMFLVSVIFFCLFLKNSSKQEKARASAETFRRAKYHNALLCLLFLFFFF
  YVGAEVTYGSYVFSFATTHAGMKESEAAGLNSIFWGTFAACRGLAIFFATCLQPGTMIVL
  SNIGSLTSSLFLVLFDKNPICLWIATSVYGASMATTFPSGVSWIEQYTTIHGKSAAFFVI
  GASLGEMAIPAVIGILQGKYPDLPVVLYTSLGASIATGILFPVLYKLATSPLDRQRKEDR
  KSEDQKALLSSSGLNEYEEENEEEDAEKWNEMDFEMIETNDTMRHSIIETSRSSLTEPTA
  EVYNQYPSNALVFESSPFNTGSAHVKHLPETRTKGTNV
• Function: May function as a sodium-dependent glucose transporter. Potential channels for urea in the inner medulla of kidney.
• Reactome Pathway: Cellular hexose transport (R-HSA-189200)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[1]
Type-1 diabetes	DIS7HLUB	moderate	Altered Expression	[2]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[3]
Psoriatic arthritis	DISLWTG2	Limited	Genetic Variation	[4]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[5]

6 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 Sodium-dependent glucose transporter 1 (MFSD4B).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sodium-dependent glucose transporter 1 (MFSD4B).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Sodium-dependent glucose transporter 1 (MFSD4B).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Sodium-dependent glucose transporter 1 (MFSD4B).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sodium-dependent glucose transporter 1 (MFSD4B).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Sodium-dependent glucose transporter 1 (MFSD4B).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Sodium-dependent glucose transporter 1 (MFSD4B).	[11]

References

• [1] The Fanconi anemia DNA damage repair pathway in the spotlight for germline predisposition to colorectal cancer.Eur J Hum Genet. 2016 Oct;24(10):1501-5. doi: 10.1038/ejhg.2016.44. Epub 2016 May 11.
• [2] Characterisation of glucose transporters in the intact coronary artery endothelium in rats: GLUT-2 upregulated by long-term hyperglycaemia.Diabetologia. 2004 Dec;47(12):2081-92. doi: 10.1007/s00125-004-1583-4. Epub 2004 Dec 10.
• [3] Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility.Nat Commun. 2015 Apr 23;6:6916. doi: 10.1038/ncomms7916.
• [4] Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis.Ann Rheum Dis. 2019 Mar;78(3):e214158. doi: 10.1136/annrheumdis-2018-214158. Epub 2018 Dec 14.
• [5] Immunochip identifies novel, and replicates known, genetic risk loci for rheumatoid arthritis in black South Africans.Mol Med. 2014 Aug 14;20(1):341-9. doi: 10.2119/molmed.2014.00097.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [9] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [12] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.