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

General Information of Drug (ID: DMU075F)

• Drug Name: Leupeptin Drug Info
• Synonyms: 2-(2-Acetamido-4-methylvaleramido)-N-(1-formyl-4-guanidinobutyl)-4-methylvaleramide; AC1L97IT; Valeramide, 2-(2-acetamido-4-methylvaleramido)-N-(1-formyl-4-guanidinobutyl)-4-methyl-; 24365-55-7; (2S)-2-acetamido-N-[1-[[5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-4-methylpentanamide

Indication

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

• Cross-matching ID:
  PubChem CID: 72429
  ChEBI ID: CHEBI:6426
  CAS Number: CAS 55123-66-5
  TTD Drug ID: DMU075F
  VARIDT Drug ID: DR01268

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pepstatin	DM9S1EA	Malaria	1F40-1F45	Terminated	[2]
Vinylsulphones	DMNFVO7	Infection of P. falciparum	1F40	Investigative	[7]
FITC-LMNNAEHINQFYMFI	DMW2VOX	Discovery agent	N.A.	Investigative	[8]

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	[9]
US9353089, 330	DMK02LS	N. A.	N. A.	Patented	[9]
US9353089, 327	DMB4MJ0	N. A.	N. A.	Patented	[9]
Pepstatin	DM9S1EA	Malaria	1F40-1F45	Terminated	[1]
E-64	DMMOPAK	Discovery agent	N.A.	Investigative	[10]
KNI-10006	DMMISH6	Discovery agent	N.A.	Investigative	[11]
PS-777621	DM3F7SD	Discovery agent	N.A.	Investigative	[12]
PS-662477	DMT4YFR	Discovery agent	N.A.	Investigative	[13]
KNI-10740	DMPWY6H	Discovery agent	N.A.	Investigative	[11]
KNI-10265	DMQLB3T	Discovery agent	N.A.	Investigative	[14]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pepstatin	DM9S1EA	Malaria	1F40-1F45	Terminated	[1]
E-64	DMMOPAK	Discovery agent	N.A.	Investigative	[10]
KNI-10006	DMMISH6	Discovery agent	N.A.	Investigative	[15]
PS-777621	DM3F7SD	Discovery agent	N.A.	Investigative	[12]
SC-5003	DM2DU80	Discovery agent	N.A.	Investigative	[16]
L-mannitol derivative	DMK12C0	Discovery agent	N.A.	Investigative	[17]

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

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

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[18]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[19]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[3]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[20]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[3]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[3]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[21]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[3]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[22]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[23]

Drug(s) Affected By Kallikrein-8 (KLK8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[24]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[25]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[26]
Potassium Chloride	DMMTAJC	Hypokalemia	5C77	Approved	[4]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[27]
Magnesium	DMU4ORS	Ischemic stroke	8B11.5Z	Approved	[4]
Magnesium Sulfate	DMVEK07	Acute pain	MG31	Approved	[4]
Permethrin	DMZ0Q1G	Pediculus capitis infestation	1G00.0	Approved	[28]
Triclosan	DMZUR4N	Malaria	1F40-1F45	Approved	[29]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[30]

Drug(s) Affected By Pro-epidermal growth factor (EGF)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[31]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[32]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[33]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[34]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[24]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[35]
Nevirapine	DM6HX9B	Human immunodeficiency virus infection	1C62	Approved	[36]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[37]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[38]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[39]

Drug(s) Affected By M-phase inducer phosphatase 3 (CDC25C)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[40]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[41]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[42]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[43]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[44]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[45]
Acetic Acid, Glacial	DM4SJ5Y	infection in the ear canal	AA0Y	Approved	[46]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[47]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[48]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[38]

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	[1]
Plasmodium Cysteine protease falcipain-2 (Malaria CPF2)	TT7EASG	Q9N6S8_PLAFA	Inhibitor	[2]
Plasmodium Plasmepsin 1 (Malaria PLA1)	TTH9VL3	PLM1_PLAFA	Inhibitor	[1]
Plasmodium Plasmepsin 2 (Malaria PLA2)	TTXMNHO	PLM2_PLAFA	Inhibitor	[1]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Kallikrein-8 (KLK8)	OTGVGHXY	KLK8_HUMAN	Gene/Protein Processing	[4]
M-phase inducer phosphatase 3 (CDC25C)	OTPQI71S	MPIP3_HUMAN	Gene/Protein Processing	[5]
Pro-epidermal growth factor (EGF)	OTANRJ0L	EGF_HUMAN	Protein Interaction/Cellular Processes	[6]

References

• [1] Novel molecular targets for antimalarial chemotherapy. Int J Antimicrob Agents. 2007 Jul;30(1):4-10.
• [2] Novel molecular targets for antimalarial drug development. Chem Biol Drug Des. 2008 Apr;71(4):287-97.
• [3] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [4] Activation and enzymatic characterization of recombinant human kallikrein 8. Biol Chem. 2006 Jun;387(6):723-31. doi: 10.1515/BC.2006.091.
• [5] Xanthatin triggers Chk1-mediated DNA damage response and destabilizes Cdc25C via lysosomal degradation in lung cancer cells. Toxicol Appl Pharmacol. 2017 Dec 15;337:85-94. doi: 10.1016/j.taap.2017.10.015. Epub 2017 Oct 23.
• [6] Targeting C4-demethylating genes in the cholesterol pathway sensitizes cancer cells to EGF receptor inhibitors via increased EGF receptor degradation. Cancer Discov. 2013 Jan;3(1):96-111. doi: 10.1158/2159-8290.CD-12-0031. Epub 2012 Nov 2.
• [7] Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
• [8] A prodomain peptide of Plasmodium falciparum cysteine protease (falcipain-2) inhibits malaria parasite development. J Med Chem. 2008 Jun 12;51(11):3116-23.
• [9] Compositions and methods for the treatment of malaria. US9353089.
• [10] Antimalarial synergy of cysteine and aspartic protease inhibitors. Antimicrob Agents Chemother. 1998 Sep;42(9):2254-8.
• [11] Improvement of both plasmepsin inhibitory activity and antimalarial activity by 2-aminoethylamino substitution. Bioorg Med Chem Lett. 2010 Aug 15;20(16):4836-9.
• [12] High antiplasmodial activity of novel plasmepsins I and II inhibitors. J Med Chem. 2006 Dec 14;49(25):7440-9.
• [13] 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.
• [14] Antimalarial activity enhancement in hydroxymethylcarbonyl (HMC) isostere-based dipeptidomimetics targeting malarial aspartic protease plasmepsin. Bioorg Med Chem. 2008 Dec 1;16(23):10049-60.
• [15] 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.
• [16] Protease inhibitors: current status and future prospects. J Med Chem. 2000 Feb 10;43(3):305-41.
• [17] Synthesis of malarial plasmepsin inhibitors and prediction of binding modes by molecular dynamics simulations. J Med Chem. 2005 Sep 22;48(19):6090-106.
• [18] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [19] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [20] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [21] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [22] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [23] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
• [24] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [25] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [26] 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.
• [27] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [28] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [29] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [30] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [31] Estradiol attenuates EGF-induced rapid uPAR mobilization and cell migration via the G-protein-coupled receptor 30 in ovarian cancer cells. Int J Gynecol Cancer. 2009 Feb;19(2):214-22. doi: 10.1111/IGC.0b013e31819bcb75.
• [32] N-O Reduction and ROS-Mediated AKT/FOXO1 and AKT/P53 Pathways Are Involved in Growth Promotion and Cytotoxicity of Cyadox. Chem Res Toxicol. 2018 Nov 19;31(11):1219-1229. doi: 10.1021/acs.chemrestox.8b00194. Epub 2018 Oct 11.
• [33] Quercetin inhibits invasion, migration and signalling molecules involved in cell survival and proliferation of prostate cancer cell line (PC-3). Cell Biochem Funct. 2011 Mar;29(2):87-95. doi: 10.1002/cbf.1725. Epub 2011 Feb 9.
• [34] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [35] Grouping of histone deacetylase inhibitors and other toxicants disturbing neural crest migration by transcriptional profiling. Neurotoxicology. 2015 Sep;50:56-70.
• [36] Nevirapine restores androgen signaling in hormone-refractory human prostate carcinoma cells both in vitro and in vivo. Prostate. 2009 May 15;69(7):744-54. doi: 10.1002/pros.20923.
• [37] 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.
• [38] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [39] 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.
• [40] Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells. Toxicol Sci. 2023 Feb 17;191(2):227-238. doi: 10.1093/toxsci/kfac131.
• [41] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [42] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [43] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [44] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [45] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [46] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [47] Arsenic trioxide-mediated growth inhibition in MC/CAR myeloma cells via cell cycle arrest in association with induction of cyclin-dependent kinase inhibitor, p21, and apoptosis. Cancer Res. 2000 Jun 1;60(11):3065-71.
• [48] Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Res. 2006 Jul 1;66(13):6615-21. doi: 10.1158/0008-5472.CAN-05-4566.