Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT2I6UX)

• DTT Name: Beta-N-acetylhexosaminidase (OGA)
• Synonyms: OGA; Nuclear cytoplasmic OGlcNAcase and acetyltransferase; Meningiomaexpressed antigen 5; MGEA5; Histone acetyltransferase; Bifunctional protein NCOAT
• Gene Name: MGEA5
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Glycosylase
• UniProt ID: OGA_HUMAN
• TTD ID: T19567
• EC Number: EC 3.2.1.169
• Sequence:
  MVQKESQATLEERESELSSNPAASAGASLEPPAAPAPGEDNPAGAGGAAVAGAAGGARRF
  LCGVVEGFYGRPWVMEQRKELFRRLQKWELNTYLYAPKDDYKHRMFWREMYSVEEAEQLM
  TLISAAREYEIEFIYAISPGLDITFSNPKEVSTLKRKLDQVSQFGCRSFALLFDDIDHNM
  CAADKEVFSSFAHAQVSITNEIYQYLGEPETFLFCPTEYCGTFCYPNVSQSPYLRTVGEK
  LLPGIEVLWTGPKVVSKEIPVESIEEVSKIIKRAPVIWDNIHANDYDQKRLFLGPYKGRS
  TELIPRLKGVLTNPNCEFEANYVAIHTLATWYKSNMNGVRKDVVMTDSEDSTVSIQIKLE
  NEGSDEDIETDVLYSPQMALKLALTEWLQEFGVPHQYSSRQVAHSGAKASVVDGTPLVAA
  PSLNATTVVTTVYQEPIMSQGAALSGEPTTLTKEEEKKQPDEEPMDMVVEKQEETDHKND
  NQILSEIVEAKMAEELKPMDTDKESIAESKSPEMSMQEDCISDIAPMQTDEQTNKEQFVP
  GPNEKPLYTAEPVTLEDLQLLADLFYLPYEHGPKGAQMLREFQWLRANSSVVSVNCKGKD
  SEKIEEWRSRAAKFEEMCGLVMGMFTRLSNCANRTILYDMYSYVWDIKSIMSMVKSFVQW
  LGCRSHSSAQFLIGDQEPWAFRGGLAGEFQRLLPIDGANDLFFQPPPLTPTSKVYTIRPY
  FPKDEASVYKICREMYDDGVGLPFQSQPDLIGDKLVGGLLSLSLDYCFVLEDEDGICGYA
  LGTVDVTPFIKKCKISWIPFMQEKYTKPNGDKELSEAEKIMLSFHEEQEVLPETFLANFP
  SLIKMDIHKKVTDPSVAKSMMACLLSSLKANGSRGAFCEVRPDDKRILEFYSKLGCFEIA
  KMEGFPKDVVILGRSL
• Function: Isoform 3: Cleaves GlcNAc but not GalNAc from O- glycosylated proteins. Can use p-nitrophenyl-beta-GlcNAc as substrate but not p-nitrophenyl-beta-GalNAc or p-nitrophenyl- alpha-GlcNAc (in vitro), but has about six times lower specific activity than isoform1. {ECO:0000269|PubMed:20673219}.
• KEGG Pathway: Insulin resistance (hsa04931)
• BioCyc Pathway: MetaCyc:HS03036-MON

Molecular Interaction Atlas (MIA) of This DTT

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LY3372689	DMA2M7V	Alzheimer disease	8A20	Phase 2	[2]
ASN51	DMZWOYL	Alzheimer disease	8A20	Phase 1	[3]
BIIB113	DM7U1AC	Alzheimer disease	8A20	Phase 1	[4]
MK 8719	DMFLP21	Progressive supranuclear palsy	8A00.10	Phase 1	[1]
MK-8719	DMETIBD	Progressive supranuclear palsy	8A00.10	Phase 1	[5]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] ClinicalTrials.gov (NCT05063539) Assessment of Safety, Tolerability, and Efficacy of LY3372689 in Early Symptomatic Alzheimer's Disease. U.S.National Institutes of Health.
• [3] Clinical pipeline report, company report or official report of Asceneuron
• [4] ClinicalTrials.gov (NCT05195008) A Phase 1 Randomized, Blinded, Placebo-Controlled, Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics, With an Open-Label Target Occupancy Study of BIIB113 in Healthy Participants. U.S.National Institutes of Health.
• [5] Discovery of MK-8719, a Potent O-GlcNAcase Inhibitor as a Potential Treatment for Tauopathies. J Med Chem. 2019 Nov 27;62(22):10062-10097.