Details of Drug Off-Target (DOT)

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

• DOT Name: Guanylate cyclase soluble subunit beta-1 (GUCY1B1)
• Synonyms: GCS-beta-1; EC 4.6.1.2; Guanylate cyclase soluble subunit beta-3; GCS-beta-3; Soluble guanylate cyclase small subunit
• Gene Name: GUCY1B1
• UniProt ID: GCYB1_HUMAN
• PDB ID: 2WZ1; 3UVJ; 4NI2; 5MNW; 6JT0; 6JT1; 6JT2; 7D9R; 7D9S; 7D9T; 7D9U; 8HBE; 8HBF; 8HBH
• EC Number: 4.6.1.2
• Pfam ID: PF00211 ; PF07700 ; PF07701
• Sequence:
  MYGFVNHALELLVIRNYGPEVWEDIKKEAQLDEEGQFLVRIIYDDSKTYDLVAAASKVLN
  LNAGEILQMFGKMFFVFCQESGYDTILRVLGSNVREFLQNLDALHDHLATIYPGMRAPSF
  RCTDAEKGKGLILHYYSEREGLQDIVIGIIKTVAQQIHGTEIDMKVIQQRNEECDHTQFL
  IEEKESKEEDFYEDLDRFEENGTQESRISPYTFCKAFPFHIIFDRDLVVTQCGNAIYRVL
  PQLQPGNCSLLSVFSLVRPHIDISFHGILSHINTVFVLRSKEGLLDVEKLECEDELTGTE
  ISCLRLKGQMIYLPEADSILFLCSPSVMNLDDLTRRGLYLSDIPLHDATRDLVLLGEQFR
  EEYKLTQELEILTDRLQLTLRALEDEKKKTDTLLYSVLPPSVANELRHKRPVPAKRYDNV
  TILFSGIVGFNAFCSKHASGEGAMKIVNLLNDLYTRFDTLTDSRKNPFVYKVETVGDKYM
  TVSGLPEPCIHHARSICHLALDMMEIAGQVQVDGESVQITIGIHTGEVVTGVIGQRMPRY
  CLFGNTVNLTSRTETTGEKGKINVSEYTYRCLMSPENSDPQFHLEHRGPVSMKGKKEPMQ
  VWFLSRKNTGTEETKQDDD
• Function: Mediates responses to nitric oxide (NO) by catalyzing the biosynthesis of the signaling molecule cGMP.
• Tissue Specificity: Detected in brain cortex and cerebellum (at protein level).
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Metabolic pathways (hsa01100)
  cGMP-PKG sig.ling pathway (hsa04022)
  Vascular smooth muscle contraction (hsa04270)
  Gap junction (hsa04540)
  Platelet activation (hsa04611)
  Circadian entrainment (hsa04713)
  Long-term depression (hsa04730)
  Oxytocin sig.ling pathway (hsa04921)
  Renin secretion (hsa04924)
  Salivary secretion (hsa04970)
• Reactome Pathway:
  Smooth Muscle Contraction (R-HSA-445355)
  Nitric oxide stimulates guanylate cyclase (R-HSA-392154)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Guanylate cyclase soluble subunit beta-1 (GUCY1B1) affects the response to substance of Cisplatin.	[16]
Mitoxantrone	DMM39BF	Approved	Guanylate cyclase soluble subunit beta-1 (GUCY1B1) affects the response to substance of Mitoxantrone.	[16]

1 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 Guanylate cyclase soluble subunit beta-1 (GUCY1B1).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Guanylate cyclase soluble subunit beta-1 (GUCY1B1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Guanylate cyclase soluble subunit beta-1 (GUCY1B1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Guanylate cyclase soluble subunit beta-1 (GUCY1B1).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Guanylate cyclase soluble subunit beta-1 (GUCY1B1).	[5]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Guanylate cyclase soluble subunit beta-1 (GUCY1B1).	[6]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Guanylate cyclase soluble subunit beta-1 (GUCY1B1).	[7]
Glyceryl trinitrate	DMF72W3	Phase 4	Glyceryl trinitrate increases the expression of Guanylate cyclase soluble subunit beta-1 (GUCY1B1).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Guanylate cyclase soluble subunit beta-1 (GUCY1B1).	[9]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Guanylate cyclase soluble subunit beta-1 (GUCY1B1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Guanylate cyclase soluble subunit beta-1 (GUCY1B1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Guanylate cyclase soluble subunit beta-1 (GUCY1B1).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Guanylate cyclase soluble subunit beta-1 (GUCY1B1).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Guanylate cyclase soluble subunit beta-1 (GUCY1B1).	[14]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Guanylate cyclase soluble subunit beta-1 (GUCY1B1).	[15]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 2008 Oct;7(10):1607-18.
• [6] Expression profiling of nucleotide metabolism-related genes in human breast cancer cells after treatment with 5-fluorouracil. Cancer Invest. 2009 Jun;27(5):561-7.
• [7] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [8] Glyceryl trinitrate treatment up-regulates soluble guanylyl cyclase in rat dura mater. Neuroreport. 2001 Dec 21;12(18):3993-6. doi: 10.1097/00001756-200112210-00028.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [10] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [11] 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.
• [12] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [13] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [14] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [15] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [16] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.