Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTE2KUJ)

• DTT Name: Adenosylhomocysteinase (AHCY)
• Synonyms: SAHH; SAH hydrolase; S-adenosyl-L-homocysteine hydrolase
• Gene Name: AHCY
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Ether bond hydrolase
• UniProt ID: SAHH_HUMAN
• TTD ID: T68698
• EC Number: EC 3.3.1.1
• Sequence:
  MSDKLPYKVADIGLAAWGRKALDIAENEMPGLMRMRERYSASKPLKGARIAGCLHMTVET
  AVLIETLVTLGAEVQWSSCNIFSTQDHAAAAIAKAGIPVYAWKGETDEEYLWCIEQTLYF
  KDGPLNMILDDGGDLTNLIHTKYPQLLPGIRGISEETTTGVHNLYKMMANGILKVPAINV
  NDSVTKSKFDNLYGCRESLIDGIKRATDVMIAGKVAVVAGYGDVGKGCAQALRGFGARVI
  ITEIDPINALQAAMEGYEVTTMDEACQEGNIFVTTTGCIDIILGRHFEQMKDDAIVCNIG
  HFDVEIDVKWLNENAVEKVNIKPQVDRYRLKNGRRIILLAEGRLVNLGCAMGHPSFVMSN
  SFTNQVMAQIELWTHPDKYPVGVHFLPKKLDEAVAEAHLGKLNVKLTKLTEKQAQYLGMS
  CDGPFKPDHYRY
• Function: Adenosylhomocysteine is a competitive inhibitor of S-adenosyl-L-methionine-dependent methyl transferase reactions; therefore adenosylhomocysteinase may play a key role in the control of methylations via regulation of the intracellular concentration of adenosylhomocysteine.
• Reactome Pathway:
  Sulfur amino acid metabolism (R-HSA-1614635)
  Metabolism of ingested SeMet, Sec, MeSec into H2Se (R-HSA-2408508)
  Defective AHCY causes HMAHCHD (R-HSA-5578997)
  Methylation (R-HSA-156581)
• BioCyc Pathway: MetaCyc:HS02273-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ARISTEROMYCIN	DMRXB74	N. A.	N. A.	Terminated	[2]

13 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-Propanol, Isopropanol	DML5O0H	Discovery agent	N.A.	Investigative	[3]
3'-Oxo-Adenosine	DM47ZWK	Discovery agent	N.A.	Investigative	[4]
4(Z)-(5'-Deoxyadenosin-5'-ylidene)butanoic acid	DM2YAUX	Discovery agent	N.A.	Investigative	[5]
5'-deoxy-5'-ureidoadenosine	DM8IQX4	Discovery agent	N.A.	Investigative	[6]
5'-S-ethyl-5'-thioadenosine	DM0PQH1	Discovery agent	N.A.	Investigative	[3]
5(E)-(5'-Deoxyadenosin-5'-ylidene)pentanoic acid	DM1IGOD	Discovery agent	N.A.	Investigative	[5]
5-methylenearisteromycin	DMIQ1X3	Discovery agent	N.A.	Investigative	[2]
D-Eritadenine	DM2XT7S	N. A.	N. A.	Investigative	[7]
DZNep	DM0JXBK	Discovery agent	N.A.	Investigative	[8]
FLUORO-NEPLANOCIN A	DM0LR7G	Discovery agent	N.A.	Investigative	[9]
Neplanocin A	DMXULGK	Discovery agent	N.A.	Investigative	[1]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	N. A.	N. A.	Investigative	[7]
NORARISTEROMYCIN	DMZ9024	Discovery agent	N.A.	Investigative	[10]

References

• [1] Molecular approaches for the treatment of hemorrhagic fever virus infections. Antiviral Res. 1993 Sep;22(1):45-75.
• [2] Synthesis of 2-modified aristeromycins and their analogs as potent inhibitors against Plasmodium falciparum S-adenosyl-L-homocysteine hydrolase. Bioorg Med Chem. 2008 Apr 1;16(7):3809-15.
• [3] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [4] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [5] Synthesis of 5'-functionalized nucleosides: S-Adenosylhomocysteine analogues with the carbon-5' and sulfur atoms replaced by a vinyl or halovinyl u... Bioorg Med Chem. 2008 May 15;16(10):5424-33.
• [6] Design, synthesis, and molecular modeling studies of 5'-deoxy-5'-ureidoadenosine: 5'-ureido group as multiple hydrogen bonding donor in the active ... Bioorg Med Chem Lett. 2007 Aug 15;17(16):4456-9.
• [7] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [8] 3-Deazaneplanocin: a new and potent inhibitor of S-adenosylhomocysteine hydrolase and its effects on human promyelocytic leukemia cell line HL-60. Biochem Biophys Res Commun. 1986 Mar 13;135(2):688-94.
• [9] Synthesis of 5'-substituted fluoro-neplanocin A analogues: importance of a hydrogen bonding donor at 5'-position for the inhibitory activity of S-a... Bioorg Med Chem Lett. 2004 Nov 15;14(22):5641-4.
• [10] Synthesis of 4'-modified noraristeromycins to clarify the effect of the 4'-hydroxyl groups for inhibitory activity against S-adenosyl-L-homocystein... Bioorg Med Chem Lett. 2008 Apr 15;18(8):2615-8.