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

General Information of Drug (ID: DM9S1EA)

• Drug Name: Pepstatin Drug Info
• Synonyms: AC1NUZ3J; L-Valinamide, N-(3-methyl-1-oxobutyl)-L-valyl-N-(4-((2-((1-(2-carboxy-1-hydroxyethyl)-3-methylbutyl)amino)-1-methyl-2-oxoethyl)amino)-2-hydroxy-1-(2-methylpropyl)-4-oxobutyl)-, (1S-(1R*,2R*,4(R*(R*(R*)))))-; N-Isovaleryl-L-valyl-L-valyl-3-hydroxy-6-methyl-gamma-aminoheptanoyl-L-alanyl-3-hydroxy-6-methyl-gamma-aminoheptanoic acid

Indication

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Terminated	[1]

• Cross-matching ID:
  PubChem CID: 5478883
  ChEBI ID: CHEBI:7989
  CAS Number: CAS 26305-03-3
  TTD Drug ID: DM9S1EA

Molecule-Related Drug Atlas

Drug(s) Targeting Plasmodium Cysteine protease falcipain-2 (Malaria CPF2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Leupeptin	DMU075F	Malaria	1F40-1F45	Investigative	[3]
Vinylsulphones	DMNFVO7	Infection of P. falciparum	1F40	Investigative	[5]
FITC-LMNNAEHINQFYMFI	DMW2VOX	Discovery agent	N.A.	Investigative	[6]

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	[7]
US9353089, 330	DMK02LS	N. A.	N. A.	Patented	[7]
US9353089, 327	DMB4MJ0	N. A.	N. A.	Patented	[7]
Leupeptin	DMU075F	Malaria	1F40-1F45	Investigative	[2]
E-64	DMMOPAK	Discovery agent	N.A.	Investigative	[8]
KNI-10006	DMMISH6	Discovery agent	N.A.	Investigative	[9]
PS-777621	DM3F7SD	Discovery agent	N.A.	Investigative	[10]
PS-662477	DMT4YFR	Discovery agent	N.A.	Investigative	[11]
KNI-10740	DMPWY6H	Discovery agent	N.A.	Investigative	[9]
KNI-10265	DMQLB3T	Discovery agent	N.A.	Investigative	[12]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Leupeptin	DMU075F	Malaria	1F40-1F45	Investigative	[2]
E-64	DMMOPAK	Discovery agent	N.A.	Investigative	[8]
KNI-10006	DMMISH6	Discovery agent	N.A.	Investigative	[13]
PS-777621	DM3F7SD	Discovery agent	N.A.	Investigative	[10]
SC-5003	DM2DU80	Discovery agent	N.A.	Investigative	[14]
L-mannitol derivative	DMK12C0	Discovery agent	N.A.	Investigative	[15]

Drug(s) Targeting Plasmodium Cysteine protease falcipain (Malaria CPF)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Leupeptin	DMU075F	Malaria	1F40-1F45	Investigative	[2]

Drug(s) Affected By Cathepsin D (CTSD)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[16]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[17]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[18]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[19]
Glucosamine	DM4ZLFD	Osteoarthritis	FA00-FA05	Approved	[20]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[21]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[22]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[23]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[24]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Plasmodium Cysteine protease falcipain (Malaria CPF)	TTJNPTK	NOUNIPROTAC	Inhibitor	[2]
Plasmodium Cysteine protease falcipain-2 (Malaria CPF2)	TT7EASG	Q9N6S8_PLAFA	Inhibitor	[3]
Plasmodium Plasmepsin 1 (Malaria PLA1)	TTH9VL3	PLM1_PLAFA	Inhibitor	[2]
Plasmodium Plasmepsin 2 (Malaria PLA2)	TTXMNHO	PLM2_PLAFA	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cathepsin D (CTSD)	OTQZ36F3	CATD_HUMAN	Gene/Protein Processing	[4]

References

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• [4] Evidence of a lysosomal pathway for apoptosis induced by the synthetic retinoid CD437 in human leukemia HL-60 cells. Cell Death Differ. 2001 May;8(5):477-85. doi: 10.1038/sj.cdd.4400843.
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• [13] 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.
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• [15] Synthesis of malarial plasmepsin inhibitors and prediction of binding modes by molecular dynamics simulations. J Med Chem. 2005 Sep 22;48(19):6090-106.
• [16] Resveratrol modulates the phosphoinositide 3-kinase pathway through an estrogen receptor alpha-dependent mechanism: relevance in cell proliferation. Int J Cancer. 2004 Mar 20;109(2):167-73. doi: 10.1002/ijc.11720.
• [17] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [18] The G protein-coupled receptor GPR30 mediates c-fos up-regulation by 17beta-estradiol and phytoestrogens in breast cancer cells. J Biol Chem. 2004 Jun 25;279(26):27008-16. doi: 10.1074/jbc.M403588200. Epub 2004 Apr 16.
• [19] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [20] Glucosamine sulfate-induced apoptosis in chronic myelogenous leukemia K562 cells is associated with translocation of cathepsin D and downregulation of Bcl-xL. Apoptosis. 2006 Oct;11(10):1851-60. doi: 10.1007/s10495-006-9529-6.
• [21] Src Family Kinase Inhibitor PP2 Has Different Effects on All-Trans-Retinoic Acid or Arsenic Trioxide-Induced Differentiation of an Acute Promyelocytic Leukemia Cell Line. Cancer Res Treat. 2013 Jun;45(2):126-33. doi: 10.4143/crt.2013.45.2.126. Epub 2013 Jun 30.
• [22] Genomic and proteomic analysis of the effects of cannabinoids on normal human astrocytes. Brain Res. 2008 Jan 29;1191:1-11.
• [23] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [24] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [25] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.