Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT46FSKD)

• DOT Name: Cystathionine beta-synthase (CBS)
• Synonyms: EC 4.2.1.22; Beta-thionase; Serine sulfhydrase
• Gene Name: CBS
• Related Disease: Classic homocystinuria
• UniProt ID: CBS_HUMAN
• PDB ID: 1JBQ; 1M54; 4COO; 4L0D; 4L27; 4L28; 4L3V; 4PCU; 4UUU; 5MMS; 7QGT; 8STW
• EC Number: 4.2.1.22
• Pfam ID: PF00571 ; PF00291
• Sequence:
  MPSETPQAEVGPTGCPHRSGPHSAKGSLEKGSPEDKEAKEPLWIRPDAPSRCTWQLGRPA
  SESPHHHTAPAKSPKILPDILKKIGDTPMVRINKIGKKFGLKCELLAKCEFFNAGGSVKD
  RISLRMIEDAERDGTLKPGDTIIEPTSGNTGIGLALAAAVRGYRCIIVMPEKMSSEKVDV
  LRALGAEIVRTPTNARFDSPESHVGVAWRLKNEIPNSHILDQYRNASNPLAHYDTTADEI
  LQQCDGKLDMLVASVGTGGTITGIARKLKEKCPGCRIIGVDPEGSILAEPEELNQTEQTT
  YEVEGIGYDFIPTVLDRTVVDKWFKSNDEEAFTFARMLIAQEGLLCGGSAGSTVAVAVKA
  AQELQEGQRCVVILPDSVRNYMTKFLSDRWMLQKGFLKEEDLTEKKPWWWHLRVQELGLS
  APLTVLPTITCGHTIEILREKGFDQAPVVDEAGVILGMVTLGNMLSSLLAGKVQPSDQVG
  KVIYKQFKQIRLTDTLGRLSHILEMDHFALVVHEQIQYHSTGKSSQRQMVFGVVTAIDLL
  NFVAAQERDQK
• Function: Hydro-lyase catalyzing the first step of the transsulfuration pathway, where the hydroxyl group of L-serine is displaced by L-homocysteine in a beta-replacement reaction to form L-cystathionine, the precursor of L-cysteine. This catabolic route allows the elimination of L-methionine and the toxic metabolite L-homocysteine. Also involved in the production of hydrogen sulfide, a gasotransmitter with signaling and cytoprotective effects on neurons.
• Tissue Specificity: In the adult strongly expressed in liver and pancreas, some expression in heart and brain, weak expression in lung and kidney. In the fetus, expressed in brain, liver and kidney.
• KEGG Pathway:
  Glycine, serine and threonine metabolism (hsa00260)
  Cysteine and methionine metabolism (hsa00270)
  Metabolic pathways (hsa01100)
  Biosynthesis of amino acids (hsa01230)
• Reactome Pathway:
  Metabolism of ingested SeMet, Sec, MeSec into H2Se (R-HSA-2408508)
  Cysteine formation from homocysteine (R-HSA-1614603)
• BioCyc Pathway: MetaCyc:HS08461-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Classic homocystinuria	DIS4CREK	Definitive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Panobinostat	DM58WKG	Approved	Cystathionine beta-synthase (CBS) increases the Platelet aggregation ADR of Panobinostat.	[30]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Milchsaure	DM462BT	Investigative	Cystathionine beta-synthase (CBS) affects the secretion of Milchsaure.	[31]

26 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 Cystathionine beta-synthase (CBS).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cystathionine beta-synthase (CBS).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cystathionine beta-synthase (CBS).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cystathionine beta-synthase (CBS).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cystathionine beta-synthase (CBS).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cystathionine beta-synthase (CBS).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Cystathionine beta-synthase (CBS).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cystathionine beta-synthase (CBS).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cystathionine beta-synthase (CBS).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Cystathionine beta-synthase (CBS).	[11]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Cystathionine beta-synthase (CBS).	[12]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Cystathionine beta-synthase (CBS).	[13]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Cystathionine beta-synthase (CBS).	[14]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Cystathionine beta-synthase (CBS).	[15]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Cystathionine beta-synthase (CBS).	[10]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Cystathionine beta-synthase (CBS).	[16]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of Cystathionine beta-synthase (CBS).	[17]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone decreases the expression of Cystathionine beta-synthase (CBS).	[18]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cystathionine beta-synthase (CBS).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cystathionine beta-synthase (CBS).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cystathionine beta-synthase (CBS).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cystathionine beta-synthase (CBS).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cystathionine beta-synthase (CBS).	[26]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cystathionine beta-synthase (CBS).	[27]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Cystathionine beta-synthase (CBS).	[28]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Cystathionine beta-synthase (CBS).	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cystathionine beta-synthase (CBS).	[20]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Cystathionine beta-synthase (CBS).	[22]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Cystathionine beta-synthase (CBS).	[24]

References

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