Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Beta-galactosidase (GLB1)
• Synonyms: Lactase; Elastin receptor 1; ELNR1; Acid beta-galactosidase
• Gene Name: GLB1
• DTT Type: Preclinical target; [1]
• UniProt ID: BGAL_HUMAN
• TTD ID: T73134
• EC Number: EC 3.2.1.23
• Sequence:
  MPGFLVRILPLLLVLLLLGPTRGLRNATQRMFEIDYSRDSFLKDGQPFRYISGSIHYSRV
  PRFYWKDRLLKMKMAGLNAIQTYVPWNFHEPWPGQYQFSEDHDVEYFLRLAHELGLLVIL
  RPGPYICAEWEMGGLPAWLLEKESILLRSSDPDYLAAVDKWLGVLLPKMKPLLYQNGGPV
  ITVQVENEYGSYFACDFDYLRFLQKRFRHHLGDDVVLFTTDGAHKTFLKCGALQGLYTTV
  DFGTGSNITDAFLSQRKCEPKGPLINSEFYTGWLDHWGQPHSTIKTEAVASSLYDILARG
  ASVNLYMFIGGTNFAYWNGANSPYAAQPTSYDYDAPLSEAGDLTEKYFALRNIIQKFEKV
  PEGPIPPSTPKFAYGKVTLEKLKTVGAALDILCPSGPIKSLYPLTFIQVKQHYGFVLYRT
  TLPQDCSNPAPLSSPLNGVHDRAYVAVDGIPQGVLERNNVITLNITGKAGATLDLLVENM
  GRVNYGAYINDFKGLVSNLTLSSNILTDWTIFPLDTEDAVRSHLGGWGHRDSGHHDEAWA
  HNSSNYTLPAFYMGNFSIPSGIPDLPQDTFIQFPGWTKGQVWINGFNLGRYWPARGPQLT
  LFVPQHILMTSAPNTITVLELEWAPCSSDDPELCAVTFVDRPVIGSSVTYDHPSKPVEKR
  LMPPPPQKNKDSWLDHV
• Function: Isoform 1: Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans.
• KEGG Pathway:
  Galactose metabolism (hsa00052)
  Other glycan degradation (hsa00511)
  Glycosaminoglycan degradation (hsa00531)
  Sphingolipid metabolism (hsa00600)
  Glycosphingolipid biosynthesis - ganglio series (hsa00604)
  Metabolic pathways (hsa01100)
  Lysosome (hsa04142)
• Reactome Pathway:
  Keratan sulfate degradation (R-HSA-2022857)
  HS-GAG degradation (R-HSA-2024096)
  MPS IV - Morquio syndrome B (R-HSA-2206308)
  Sialic acid metabolism (R-HSA-4085001)
  Defective NEU1 causes sialidosis (R-HSA-4341670)
  Neutrophil degranulation (R-HSA-6798695)
  Glycosphingolipid metabolism (R-HSA-1660662)

Molecular Interaction Atlas (MIA) of This DTT

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AXO-AAV-GM1	DMFBMI7	GM1 gangliosidosis	5C56.00	Phase 1/2	[2]
LYS-GM-101	DMPD79C	GM1 gangliosidosis	5C56.00	Phase 1/2	[3]
PBGM01	DMNJEGV	GM1 gangliosidosis	5C56.00	Phase 1/2	[4]

2 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
5N,6S-(N'-butyliminomethylidene)-6-thio-1-deoxygalactonojirimycin	DM7RHOC	GM1 gangliosidosis	5C56.00	Preclinical	[5]
N-Octyl-4-epi-beta-valienamine	DMTQ2UD	GM1 gangliosidosis	5C56.00	Preclinical	[6]

References

• [1] Turnover of beta-galactosidase in fibroblasts from patients with genetically different types of beta-galactosidase deficiency. Biochem J. 1981 Oct 15;200(1):143-51.
• [2] Clinical pipeline report, company report or official report of Axovant Gene Therapies
• [3] ClinicalTrials.gov (NCT04273269) An Open-Label Adaptive-Design Study of Intracisternal Adenoassociated Viral Vector Serotype rh.10 Carrying the Human beta-Galactosidase cDNA for Treatment of GM1 Gangliosidosis. U.S.National Institutes of Health.
• [4] Clinical pipeline report, company report or official report of Passage Bio
• [5] A bicyclic 1-deoxygalactonojirimycin derivative as a novel pharmacological chaperone for GM1 gangliosidosis. Mol Ther. 2013 Mar;21(3):526-32.
• [6] Chemical modification of the beta-glucocerebrosidase inhibitor N-octyl-beta-valienamine: synthesis and biological evaluation of 4-epimeric and 4-O-(beta-D-galactopyranosyl) derivatives. Bioorg Med Chem. 2002 Jun;10(6):1967-72.