Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT5FLYB)

• DTT Name: Staphylococcus Alpha-hemolysin (Stap-coc hly)
• Synonyms: hla; Alpha-toxin; Alpha-hemolysin; Alpha-HL
• Gene Name: Stap-coc hly
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Alpha-hemolysin channel-forming toxin
• UniProt ID: HLA_STAAU
• TTD ID: T04321
• Sequence:
  MKTRIVSSVTTTLLLGSILMNPVAGAADSDINIKTGTTDIGSNTTVKTGDLVTYDKENGM
  HKKVFYSFIDDKNHNKKLLVIRTKGTIAGQYRVYSEEGANKSGLAWPSAFKVQLQLPDNE
  VAQISDYYPRNSIDTKEYMSTLTYGFNGNVTGDDTGKIGGLIGANVSIGHTLKYVQPDFK
  TILESPTDKKVGWKVIFNNMVNQNWGPYDRDSWNPVYGNQLFMKTRNGSMKAADNFLDPN
  KASSLLSSGFSPDFATVITMDRKASKQQTNIDVIYERVRDDYQLHWTSTNWKGTNTKDKW
  TDRSSERYKIDWEKEEMTN
• Function: Alpha-toxin binds to the membrane of eukaryotic cells (particularly red blood cells, RBC) forming pores, resulting in hemolysis, with the release of low-molecular weight molecules leading to eventual osmotic RBC lysis. Human RBCs bind much less alpha-toxin than do rabbit RBCs. Heptamer oligomerization and pore formation is required for lytic activity.
• Reactome Pathway: The NLRP3 inflammasome (R-HSA-844456)

Molecular Interaction Atlas (MIA) of This DTT

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AR-301	DM2YQK8	Ventilator-associated pneumonia	PK81.0	Phase 3	[2]
Cyrtominetin	DM0JA9N	Phlegmy cough	SA80-SA8Z	Phase 3	[1]
MEDI4893	DMXB4NL	Ventilator-associated pneumonia	PK81.0	Phase 2b	[3]
ASN100	DMWPGLS	Hospital-acquired pneumonia	CA40.Z	Phase 2	[4]

References

• [1] Molecular insight into the inhibition mechanism of cyrtominetin to alpha-hemolysin by molecular dynamics simulation. Eur J Med Chem. 2013 Apr;62:320-8.
• [2] Clinical pipeline report, company report or official report of Aridis Pharmaceuticals.
• [3] Mechanisms of neutralization of a human anti-alpha-toxin antibody. J Biol Chem. 2014 Oct 24;289(43):29874-80.
• [4] Antibacterial antibodies gain traction. Nat Rev Drug Discov. 2015 Nov;14(11):737-8.