Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTWNFC2)

• DTT Name: Soluble guanylyl cyclase (GUCY2D)
• Synonyms: Rod outer segment membrane guanylate cyclase; Retinal guanylyl cyclase 1; ROS-GC; RETGC1; RETGC-1; RETGC; Guanylate cyclase 2D, retinal; GUC2D; GUC1A4; CORD6
• Gene Name: GUCY2D
• DTT Type: Successful target; [1]
• UniProt ID: GUC2D_HUMAN
• TTD ID: T19693
• EC Number: EC 4.6.1.2
• Sequence:
  MTACARRAGGLPDPGLCGPAWWAPSLPRLPRALPRLPLLLLLLLLQPPALSAVFTVGVLG
  PWACDPIFSRARPDLAARLAAARLNRDPGLAGGPRFEVALLPEPCRTPGSLGAVSSALAR
  VSGLVGPVNPAACRPAELLAEEAGIALVPWGCPWTQAEGTTAPAVTPAADALYALLRAFG
  WARVALVTAPQDLWVEAGRSLSTALRARGLPVASVTSMEPLDLSGAREALRKVRDGPRVT
  AVIMVMHSVLLGGEEQRYLLEAAEELGLTDGSLVFLPFDTIHYALSPGPEALAALANSSQ
  LRRAHDAVLTLTRHCPSEGSVLDSLRRAQERRELPSDLNLQQVSPLFGTIYDAVFLLARG
  VAEARAAAGGRWVSGAAVARHIRDAQVPGFCGDLGGDEEPPFVLLDTDAAGDRLFATYML
  DPARGSFLSAGTRMHFPRGGSAPGPDPSCWFDPNNICGGGLEPGLVFLGFLLVVGMGLAG
  AFLAHYVRHRLLHMQMVSGPNKIILTVDDITFLHPHGGTSRKVAQGSRSSLGARSMSDIR
  SGPSQHLDSPNIGVYEGDRVWLKKFPGDQHIAIRPATKTAFSKLQELRHENVALYLGLFL
  ARGAEGPAALWEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHR
  GVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQLWTAPELLRDPALE
  RRGTLAGDVFSLAIIMQEVVCRSAPYAMLELTPEEVVQRVRSPPPLCRPLVSMDQAPVEC
  ILLMKQCWAEQPELRPSMDHTFDLFKNINKGRKTNIIDSMLRMLEQYSSNLEDLIRERTE
  ELELEKQKTDRLLTQMLPPSVAEALKTGTPVEPEYFEQVTLYFSDIVGFTTISAMSEPIE
  VVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPQRNGQRHAAEIANMSLDILSAV
  GTFRMRHMPEVPVRIRIGLHSGPCVAGVVGLTMPRYCLFGDTVNTASRMESTGLPYRIHV
  NLSTVGILRALDSGYQVELRGRTELKGKGAEDTFWLVGRRGFNKPIPKPPDLQPGSSNHG
  ISLQEIPPERRRKLEKARPGQFS
• Function: Probably plays a specific functional role in the rods and/or cones of photoreceptors. It may be the enzyme involved in the resynthesis of cGMP required for recovery of the dark state after phototransduction.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Metabolic pathways (hsa01100)
  Olfactory transduction (hsa04740)
  Phototransduction (hsa04744)
• Reactome Pathway: Inactivation, recovery and regulation of the phototransduction cascade (R-HSA-2514859)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Riociguat	DMXBLMP	Chronic thromboembolic pulmonary hypertension		Approved	[1]
Vericiguat	DM7MDBE	Heart failure	BD10-BD13	Approved	[2]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
FK-409	DMKVXYS	Angina pectoris	BA40	Phase 2	[3]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BAY412272	DM0M59T	Discovery agent	N.A.	Investigative	[4]
NS 2028	DML0N7D	Discovery agent	N.A.	Investigative	[5]
ODQ	DMSAJO8	Discovery agent	N.A.	Investigative	[6]

References

• [1] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [3] Vasorelaxant mechanism of the new vasodilator, FK409. Eur J Pharmacol. 1993 Aug 15;246(3):205-12.
• [4] NO-independent regulatory site on soluble guanylate cyclase. Nature. 2001 Mar 8;410(6825):212-5.
• [5] Characterization of NS 2028 as a specific inhibitor of soluble guanylyl cyclase. Br J Pharmacol. 1998 Jan;123(2):299-309.
• [6] Potent and selective inhibition of nitric oxide-sensitive guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. Mol Pharmacol. 1995 Aug;48(2):184-8.