Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTH9VL3)

• DTT Name: Plasmodium Plasmepsin 1 (Malaria PLA1)
• Synonyms: Plasmepsin I; PFAPG; Aspartic hemoglobinase I
• Gene Name: Malaria PLA1
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Peptidase
• UniProt ID: PLM1_PLAFA
• TTD ID: T50547
• Sequence:
  MALSIKEDFSSAFAKNESAVNSSTFNNNMKTWKIQKRFQILYVFFFLLITGALFYYLIDN
  VLFPKNKKINEIMNTSKHVIIGFSIENSHDRIMKTVKQHRLKNYIKESLKFFKTGLTQKP
  HLGNAGDSVTLNDVANVMYYGEAQIGDNKQKFAFIFDTGSANLWVPSAQCNTIGCKTKNL
  YDSNKSKTYEKDGTKVEMNYVSGTVSGFFSKDIVTIANLSFPYKFIEVTDTNGFEPAYTL
  GQFDGIVGLGWKDLSIGSVDPVVVELKNQNKIEQAVFTFYLPFDDKHKGYLTIGGIEDRF
  YEGQLTYEKLNHDLYWQVDLDLHFGNLTVEKATAIVDSGTSSITAPTEFLNKFFEGLDVV
  KIPFLPLYITTCNNPKLPTLEFRSATNVYTLEPEYYLQQIFDFGISLCMVSIIPVDLNKN
  TFILGDPFMRKYFTVFDYDNHTVGFALAKKKL
• Function: Participates in the digestion of the host hemoglobin. Initial cleavage at the hinge region of hemoglobin, than cleaves at other sites, leading to denaturation of the molecule and to further degradation.
• BioCyc Pathway: MetaCyc:MON-15375

Molecular Interaction Atlas (MIA) of This DTT

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pepstatin	DM9S1EA	Malaria	1F40-1F45	Terminated	[1]

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
E-64	DMMOPAK	Discovery agent	N.A.	Investigative	[2]
KNI-10006	DMMISH6	Discovery agent	N.A.	Investigative	[3]
L-mannitol derivative	DMK12C0	Discovery agent	N.A.	Investigative	[4]
Leupeptin	DMU075F	Malaria	1F40-1F45	Investigative	[1]
PS-777621	DM3F7SD	Discovery agent	N.A.	Investigative	[5]
SC-5003	DM2DU80	Discovery agent	N.A.	Investigative	[6]

References

• [1] Novel molecular targets for antimalarial chemotherapy. Int J Antimicrob Agents. 2007 Jul;30(1):4-10.
• [2] Antimalarial synergy of cysteine and aspartic protease inhibitors. Antimicrob Agents Chemother. 1998 Sep;42(9):2254-8.
• [3] alpha-Substituted norstatines as the transition-state mimic in inhibitors of multiple digestive vacuole malaria aspartic proteases. Bioorg Med Chem. 2009 Aug 15;17(16):5933-49.
• [4] Synthesis of malarial plasmepsin inhibitors and prediction of binding modes by molecular dynamics simulations. J Med Chem. 2005 Sep 22;48(19):6090-106.
• [5] High antiplasmodial activity of novel plasmepsins I and II inhibitors. J Med Chem. 2006 Dec 14;49(25):7440-9.
• [6] Protease inhibitors: current status and future prospects. J Med Chem. 2000 Feb 10;43(3):305-41.