Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMMISH6)

• Drug Name: KNI-10006 Drug Info
• Synonyms: KNI-10006; CHEMBL231522; (4r)-3-[(2s,3s)-3-{[(2,6-Dimethylphenoxy)acetyl]amino}-2-Hydroxy-4-Phenylbutanoyl]-N-[(1s,2r)-2-Hydroxy-2,3-Dihydro-1h-Inden-1-Yl]-5,5-Dimethyl-1,3-Thiazolidine-4-Carboxamide; 3kdb; 3fnu; 3qs1; SCHEMBL13788265; BDBM50209559; 461444-55-3

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 9895503
  TTD Drug ID: DMMISH6

Molecule-Related Drug Atlas

Drug(s) Targeting Plasmodium Plasmepsin 2 (Malaria PLA2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
US9353089, 135	DMWG98Z	N. A.	N. A.	Patented	[3]
US9353089, 330	DMK02LS	N. A.	N. A.	Patented	[3]
US9353089, 327	DMB4MJ0	N. A.	N. A.	Patented	[3]
Pepstatin	DM9S1EA	Malaria	1F40-1F45	Terminated	[4]
Leupeptin	DMU075F	Malaria	1F40-1F45	Investigative	[4]
E-64	DMMOPAK	Discovery agent	N.A.	Investigative	[5]
PS-777621	DM3F7SD	Discovery agent	N.A.	Investigative	[6]
PS-662477	DMT4YFR	Discovery agent	N.A.	Investigative	[7]
KNI-10740	DMPWY6H	Discovery agent	N.A.	Investigative	[2]
KNI-10265	DMQLB3T	Discovery agent	N.A.	Investigative	[8]

Drug(s) Targeting Plasmodium Plasmepsin 1 (Malaria PLA1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pepstatin	DM9S1EA	Malaria	1F40-1F45	Terminated	[4]
Leupeptin	DMU075F	Malaria	1F40-1F45	Investigative	[4]
E-64	DMMOPAK	Discovery agent	N.A.	Investigative	[5]
PS-777621	DM3F7SD	Discovery agent	N.A.	Investigative	[6]
SC-5003	DM2DU80	Discovery agent	N.A.	Investigative	[9]
L-mannitol derivative	DMK12C0	Discovery agent	N.A.	Investigative	[10]

Drug(s) Targeting Cathepsin D (CTSD)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID10498202C1	DMXE0F2	Multiple sclerosis	8A40	Clinical trial	[11]
CI-992	DMBHYIJ	Hypertension	BA00-BA04	Terminated	[12]
Alpha-D-Mannose	DMF5DLW	Discovery agent	N.A.	Investigative	[13]
Grassystatin a	DM1PWX2	Discovery agent	N.A.	Investigative	[14]
PMID8410973C3	DM6J5KY	Discovery agent	N.A.	Investigative	[15]
GRL-7234	DMR93MK	Discovery agent	N.A.	Investigative	[16]
S-Methylcysteine	DMAMRKS	Discovery agent	N.A.	Investigative	[13]
Carbocyclic Peptidomimetic	DM87SOX	Discovery agent	N.A.	Investigative	[17]
N-Aminoethylmorpholine	DMWXBYC	Discovery agent	N.A.	Investigative	[13]
1h-Benoximidazole-2-Carboxylic Acid	DMNZAVE	Discovery agent	N.A.	Investigative	[13]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cathepsin D (CTSD)	TTPT2QI	CATD_HUMAN	Inhibitor	[1]
Plasmodium Plasmepsin 1 (Malaria PLA1)	TTH9VL3	PLM1_PLAFA	Inhibitor	[1]
Plasmodium Plasmepsin 2 (Malaria PLA2)	TTXMNHO	PLM2_PLAFA	Inhibitor	[2]

References

• [1] 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.
• [2] Improvement of both plasmepsin inhibitory activity and antimalarial activity by 2-aminoethylamino substitution. Bioorg Med Chem Lett. 2010 Aug 15;20(16):4836-9.
• [3] Compositions and methods for the treatment of malaria. US9353089.
• [4] Novel molecular targets for antimalarial chemotherapy. Int J Antimicrob Agents. 2007 Jul;30(1):4-10.
• [5] Antimalarial synergy of cysteine and aspartic protease inhibitors. Antimicrob Agents Chemother. 1998 Sep;42(9):2254-8.
• [6] High antiplasmodial activity of novel plasmepsins I and II inhibitors. J Med Chem. 2006 Dec 14;49(25):7440-9.
• [7] Identification of potent inhibitors of Plasmodium falciparum plasmepsin II from an encoded statine combinatorial library. Bioorg Med Chem Lett. 1998 Sep 8;8(17):2315-20.
• [8] Antimalarial activity enhancement in hydroxymethylcarbonyl (HMC) isostere-based dipeptidomimetics targeting malarial aspartic protease plasmepsin. Bioorg Med Chem. 2008 Dec 1;16(23):10049-60.
• [9] Protease inhibitors: current status and future prospects. J Med Chem. 2000 Feb 10;43(3):305-41.
• [10] Synthesis of malarial plasmepsin inhibitors and prediction of binding modes by molecular dynamics simulations. J Med Chem. 2005 Sep 22;48(19):6090-106.
• [11] Synthesis and structure activity relationships of novel small molecule cathepsin D inhibitors. Bioorg Med Chem Lett. 1999 Sep 6;9(17):2531-6.
• [12] Structure-activity relationships of a series of 2-amino-4-thiazole-containing renin inhibitors. J Med Chem. 1992 Jul 10;35(14):2562-72.
• [13] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [14] Grassystatins A-C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation. J Med Chem. 2009 Sep 24;52(18):5732-47.
• [15] Specificity in the binding of inhibitors to the active site of human/primate aspartic proteinases: analysis of P2-P1-P1'-P2' variation. J Med Chem. 1993 Sep 3;36(18):2614-20.
• [16] Design, synthesis, and X-ray structure of potent memapsin 2 (beta-secretase) inhibitors with isophthalamide derivatives as the P2-P3-ligands. J Med Chem. 2007 May 17;50(10):2399-407.
• [17] Structure-based design, synthesis, and memapsin 2 (BACE) inhibitory activity of carbocyclic and heterocyclic peptidomimetics. J Med Chem. 2005 Aug 11;48(16):5175-90.