2-Acetylamino-4-methyl-pentanoic acid [1-(1-formyl-4-guanidino-butylcarbamoyl)-3-methyl-butyl]-amide

ID: ALA191881

Chembl Id: CHEMBL191881

Cas Number: 24365-47-7

PubChem CID: 72429

Max Phase: Preclinical

Molecular Formula: C20H38N6O4

Molecular Weight: 426.56

Molecule Type: Protein

Associated Items:

Names and Identifiers

Synonyms: Leupeptin | Leupeptin|55123-66-5|Leupeptin hemisulfate|CHEBI:6426|Ac-Leu-Leu-Arg-H|Leupeptin Ac-LL|24365-47-7|103476-89-7|(2S)-2-acetamido-N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-4-methylpentanamide|J97339NR3V|acetyl-l-leucyl-l-leucyl-l-argininal|N-Acetyl-L-leucyl-L-leucyl-L-argininal|Acetyl-L-leucyl-L-leucylargininal|Leupeptin (hemisulfate)|(S)-2-Acetamido-N-((S)-1-((S)-5-guanidino-1-oxopentan-2-ylamino)-4-methyl-1-oxopentan-2-yl)-4-methylShow More

Canonical SMILES:  CC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCNC(=N)N

Standard InChI:  InChI=1S/C20H38N6O4/c1-12(2)9-16(24-14(5)28)19(30)26-17(10-13(3)4)18(29)25-15(11-27)7-6-8-23-20(21)22/h11-13,15-17H,6-10H2,1-5H3,(H,24,28)(H,25,29)(H,26,30)(H4,21,22,23)/t15-,16-,17-/m0/s1

Standard InChI Key:  GDBQQVLCIARPGH-ULQDDVLXSA-N

Alternative Forms

  1. Parent:

    ALA191881

    LEUPEPTIN
  2. Alternative Forms:

    ALA191881

    ---
  3. ALA191881

    Leupeptin

Associated Targets(Human)

CAPN1 Tchem Calpain 1 (1269 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HeLa (62764 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CTSB Tchem Cathepsin B (3822 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CTSL Tclin Cathepsin L (3852 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KLKB1 Tclin Plasma kallikrein (2047 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CTSK Tchem Cathepsin K (3011 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PLG Tclin Plasminogen (2339 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
TMPRSS6 Tchem Transmembrane protease serine 6 (209 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ST14 Tchem Matriptase (677 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
RUNX1 Tbio Runt-related transcription factor 1/Core-binding factor subunit beta (7867 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CTSH Tchem Cathepsin H (179 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HGFAC Tchem Hepatocyte growth factor activator (149 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HPN Tchem Serine protease hepsin (242 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PRSS1 Tclin Trypsin (2137 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Human rhinovirus sp. (1587 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Alpha-chymotrypsin (819 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PRSS1 Trypsin I (1205 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
F2 Thrombin (1630 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PLG Plasminogen (18 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CTSB Cathepsin B (273 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Plasmodium falciparum (966862 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Falcipain 2 (539 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Mus musculus (284745 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CAPN1 Calpain 1 (219 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Cysteine protease (30 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
protease Human rhinovirus A protease (1343 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Plasmodium berghei (192651 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Cysteine protease falcipain-3 (103 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CTSB Cathepsin B (109 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CTSH Cathepsin H (102 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Trypsin (394 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Papain (844 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: YesOral: NoChemical Probe: NoParenteral: No
Molecule Type: ProteinTopical: NoFirst In Class: NoBlack Box: No
Chirality: NoAvailability: NoProdrug: No

Drug Indications

MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

Mechanisms of Action

Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

Calculated Properties

Molecular Weight: 426.56Molecular Weight (Monoisotopic): 426.2955AlogP: 0.02#Rotatable Bonds: 14
Polar Surface Area: 166.27Molecular Species: BASEHBA: 5HBD: 6
#RO5 Violations: 1HBA (Lipinski): 10HBD (Lipinski): 7#RO5 Violations (Lipinski): 1
CX Acidic pKa: 12.35CX Basic pKa: 11.90CX LogP: -0.77CX LogD: -2.81
Aromatic Rings: Heavy Atoms: 30QED Weighted: 0.10Np Likeness Score: 0.53

References

1. McConnell RM, York JL, Frizzell D, Ezell C..  (1993)  Inhibition studies of some serine and thiol proteinases by new leupeptin analogues.,  36  (8): [PMID:8478905] [10.1021/jm00060a016]
2. Woo J, Sigeizumi S, Yamaguchi K, Sugimoto K, Kobori T, Tsuji T, Kondo K.  (1995)  Peptidyl aldehyde derivatives as potent and selective inhibitors of cathepsin L,  (14): [10.1016/0960-894X(95)00236-M]
3. Shepherd TA, Cox GA, McKinney E, Tang J, Wakulchik M, Zimmerman RE, Villarreal EC.  (1996)  Small peptidic aldehyde inhibitors of human rhinovirus 3C protease,  (23): [10.1016/S0960-894X(96)00537-9]
4. Fusetani N, Fujita M, Nakao Y, Matsunaga S, Van Soest RW..  (1999)  Tokaramide A, a new cathepsin B inhibitor from the marine sponge Theonella aff. mirabilis.,  (24): [PMID:10617079] [10.1016/s0960-894x(99)00618-6]
5. Graybill TL, Dolle RE, Osifo IK, Schmidt SJ, Gregory JS, Harris AL, Miller MS.  (1995)  Inhibition of human erythrocyte calpain I by novel quinolinecarboxamides,  (4): [10.1016/0960-894X(95)00041-Q]
6. Yasuma T, Oi S, Choh N, Nomura T, Furuyama N, Nishimura A, Fujisawa Y, Sohda T..  (1998)  Synthesis of peptide aldehyde derivatives as selective inhibitors of human cathepsin L and their inhibitory effect on bone resorption.,  41  (22): [PMID:9784105] [10.1021/jm9803065]
7. Domínguez JN, León C, Rodrigues J, Gamboa de Domínguez N, Gut J, Rosenthal PJ..  (2005)  Synthesis and evaluation of new antimalarial phenylurenyl chalcone derivatives.,  48  (10): [PMID:15887974] [10.1021/jm058208o]
8. Lescop C, Herzner H, Siendt H, Bolliger R, Henneböhle M, Weyermann P, Briguet A, Courdier-Fruh I, Erb M, Foster M, Meier T, Magyar JP, von Sprecher A..  (2005)  Novel cell-penetrating alpha-keto-amide calpain inhibitors as potential treatment for muscular dystrophy.,  15  (23): [PMID:16185867] [10.1016/j.bmcl.2005.08.064]
9. Desai PV, Patny A, Gut J, Rosenthal PJ, Tekwani B, Srivastava A, Avery M..  (2006)  Identification of novel parasitic cysteine protease inhibitors by use of virtual screening. 2. The available chemical directory.,  49  (5): [PMID:16509575] [10.1021/jm0505765]
10. Zeng GZ, Tan NH, Hao XJ, Mu QZ, Li RT..  (2006)  Natural inhibitors targeting osteoclast-mediated bone resorption.,  16  (24): [PMID:17027271] [10.1016/j.bmcl.2006.09.042]
11. León C, Rodrigues J, Gamboa de Domínguez N, Charris J, Gut J, Rosenthal PJ, Domínguez JN..  (2007)  Synthesis and evaluation of sulfonylurea derivatives as novel antimalarials.,  42  (6): [PMID:17321641] [10.1016/j.ejmech.2007.01.001]
12. Maugeri C, Alisi MA, Apicella C, Cellai L, Dragone P, Fioravanzo E, Florio S, Furlotti G, Mangano G, Ombrato R, Luisi R, Pompei R, Rincicotti V, Russo V, Vitiello M, Cazzolla N..  (2008)  New anti-viral drugs for the treatment of the common cold.,  16  (6): [PMID:18248816] [10.1016/j.bmc.2007.12.030]
13. Le GT, Abbenante G, Fairlie DP..  (2007)  Profiling the enzymatic properties and inhibition of human complement factor B.,  282  (48): [PMID:17921140] [10.1074/jbc.m705646200]
14. Martins FT, Assis DM, Dos Santos MH, Camps I, Veloso MP, Juliano MA, Alves LC, Doriguetto AC..  (2009)  Natural polyprenylated benzophenones inhibiting cysteine and serine proteases.,  44  (3): [PMID:18995931] [10.1016/j.ejmech.2008.09.018]
15. Osaki N, Koyano T, Kowithayakorn T, Hayashi M, Komiyama K, Ishibashi M..  (2005)  Sesquiterpenoids and plasmin-inhibitory flavonoids from Blumea balsamifera.,  68  (3): [PMID:15787457] [10.1021/np049622e]
16. Barazarte A, Camacho J, Domínguez J, Lobo G, Gamboa N, Rodrigues J, Capparelli MV, Alvarez-Larena A, Andujar S, Enriz D, Charris J..  (2008)  Synthesis, antimalarial activity, structure-activity relationship analysis of thieno-[3,2-b]benzothiazine S,S-dioxide analogs.,  16  (7): [PMID:18314337] [10.1016/j.bmc.2008.02.011]
17. Dominguez JN, Leon C, Rodrigues J, Gamboa de Dominguez N, Gut J, Rosenthal PJ..  (2009)  Synthesis of chlorovinyl sulfones as structural analogs of chalcones and their antiplasmodial activities.,  44  (4): [PMID:19036479] [10.1016/j.ejmech.2008.09.044]
18. Barazarte A, Lobo G, Gamboa N, Rodrigues JR, Capparelli MV, Alvarez-Larena A, López SE, Charris JE..  (2009)  Synthesis and antimalarial activity of pyrazolo and pyrimido benzothiazine dioxide derivatives.,  44  (3): [PMID:18835067] [10.1016/j.ejmech.2008.08.005]
19. Sisay MT, Steinmetzer T, Stirnberg M, Maurer E, Hammami M, Bajorath J, Gütschow M..  (2010)  Identification of the first low-molecular-weight inhibitors of matriptase-2.,  53  (15): [PMID:20684597] [10.1021/jm100183e]
20. PubChem BioAssay data set, 
21. Camacho J, Barazarte A, Gamboa N, Rodrigues J, Rojas R, Vaisberg A, Gilman R, Charris J..  (2011)  Synthesis and biological evaluation of benzimidazole-5-carbohydrazide derivatives as antimalarial, cytotoxic and antitubercular agents.,  19  (6): [PMID:21334900] [10.1016/j.bmc.2011.01.050]
22. Lisk G, Pain M, Gluzman IY, Kambhampati S, Furuya T, Su XZ, Fay MP, Goldberg DE, Desai SA..  (2008)  Changes in the plasmodial surface anion channel reduce leupeptin uptake and can confer drug resistance in Plasmodium falciparum-infected erythrocytes.,  52  (7): [PMID:18443109] [10.1128/aac.00057-08]
23. Rizzi L, Sundararaman S, Cendic K, Vaiana N, Korde R, Sinha D, Mohmmed A, Malhotra P, Romeo S..  (2011)  Design and synthesis of protein-protein interaction mimics as Plasmodium falciparum cysteine protease, falcipain-2 inhibitors.,  46  (6): [PMID:21429631] [10.1016/j.ejmech.2011.02.061]
24. Dana D, Davalos AR, De S, Rathod P, Gamage RK, Huestis J, Afzal N, Zavlanov Y, Paroly SS, Rotenberg SA, Subramaniam G, Mark KJ, Chang EJ, Kumar S..  (2013)  Development of cell-active non-peptidyl inhibitors of cysteine cathepsins.,  21  (11): [PMID:23623677] [10.1016/j.bmc.2013.03.062]
25. Raghav N, Singh M..  (2014)  Acyl hydrazides and triazoles as novel inhibitors of mammalian cathepsin B and cathepsin H.,  77  [PMID:24642566] [10.1016/j.ejmech.2014.03.007]
26. Liu L, Jokela J, Wahlsten M, Nowruzi B, Permi P, Zhang YZ, Xhaard H, Fewer DP, Sivonen K..  (2014)  Nostosins, Trypsin Inhibitors Isolated from the Terrestrial Cyanobacterium Nostoc sp. Strain FSN.,  77  (8): [PMID:25069058] [10.1021/np500106w]
27. Raghav N, Singh M..  (2014)  SAR studies of differently functionalized chalcones based hydrazones and their cyclized derivatives as inhibitors of mammalian cathepsin B and cathepsin H.,  22  (15): [PMID:24913985] [10.1016/j.bmc.2014.05.037]
28. Han Z, Harris PK, Jones DE, Chugani R, Kim T, Agarwal M, Shen W, Wildman SA, Janetka JW..  (2014)  Inhibitors of HGFA, Matriptase, and Hepsin Serine Proteases: A Nonkinase Strategy to Block Cell Signaling in Cancer.,  (11): [PMID:25408834] [10.1021/ml500254r]
29. Kruglyak N, Williams DE, Chen H, Law S, Kaleta J, Villanueva I, Davies JE, Andersen RJ, Brömme D..  (2017)  Leupeptazin, a highly modified tripeptide isolated from cultures of a Streptomyces sp. inhibits cathepsin K.,  27  (6): [PMID:28228366] [10.1016/j.bmcl.2017.02.007]
30. Steinmetzer T, Pilgram O, Wenzel BM, Wiedemeyer SJA..  (2020)  Fibrinolysis Inhibitors: Potential Drugs for the Treatment and Prevention of Bleeding.,  63  (4): [PMID:31658420] [10.1021/acs.jmedchem.9b01060]
31. Juettner NE,Bogen JP,Bauer TA,Knapp S,Pfeifer F,Huettenhain SH,Meusinger R,Kraemer A,Fuchsbauer HL.  (2020)  Decoding the Papain Inhibitor from Streptomyces mobaraensis as Being Hydroxylated Chymostatin Derivatives: Purification, Structure Analysis, and Putative Biosynthetic Pathway.,  83  (10): [PMID:32998509] [10.1021/acs.jnatprod.0c00201]
32.  (2021)  Compositions and methods for measuring and inhibiting calpain-5 activity, 
33. Phan CS, Mehjabin JJ, Anas ARJ, Hayasaka M, Onoki R, Wang J, Umezawa T, Washio K, Morikawa M, Okino T..  (2022)  Nostosin G and Spiroidesin B from the Cyanobacterium Dolichospermum sp. NIES-1697.,  85  (8.0): [PMID:35948062] [10.1021/acs.jnatprod.2c00382]
34. Chen QY, Luo D, Seabra GM, Luesch H..  (2020)  Ahp-Cyclodepsipeptides as tunable inhibitors of human neutrophil elastase and kallikrein 7: Total synthesis of tutuilamide A, serine protease selectivity profile and comparison with lyngbyastatin 7.,  28  (23.0): [PMID:33002682] [10.1016/j.bmc.2020.115756]