m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03524
 [1], [2]
Histone modification H3K4me3 WDR5 METTL3 Direct Enhancement m6A modification CTSL CTSL METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Procathepsin L (CTSL)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator WD repeat-containing protein 5 (WDR5) WRITER View Details
Regulated Target Histone H3 lysine 4 trimethylation (H3K4me3) View Details
Downstream Gene METTL3 View Details
Crosstalk Relationship Histone modification  →  m6A Enhancement
Crosstalk Mechanism histone modification directly impacts m6A modification through modulating the level of m6A regulator
Crosstalk Summary The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METTL3 mediated the m6A modification of cathepsin L (Procathepsin L (CTSL)) mRNA at the 5'-UTR, and the m6A reader protein insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) bound to the m6A sites and enhanced CTSL mRNA stability. Our results indicated that METTL3 enhanced CTSL mRNA stability through an m6A-IGF2BP2-dependent mechanism, thereby promoting cervical cancer cell metastasis.
Responsed Disease Cervical cancer ICD-11: 2C77
 Disease Info 
In-vitro Model
 Ca Ski Cervical squamous cell carcinoma Homo sapiens CVCL_1100
SiHa Cervical squamous cell carcinoma Homo sapiens CVCL_0032
HEK293-FT Normal Homo sapiens CVCL_6911
In-vivo Model Female BALB/c nude mice (4-5 weeks old) were purchased from the Center of Experimental Animals of Guangdong. To establish a tail vein metastasis model, 2 × 106 SiHa cells in 200 μ l PBS were injected into the tail vein of each mouse (n = 6 for both METTL3-overexpressing and empty vector groups). The mice were killed at approximately 8 weeks, and lung tissues were isolated and embedded in paraffin. Hematoxylin and eosin staining was then used to determine the number of lung metastasis nodules. To establish the popliteal lymph node metastasis model, 1 × 106 SiHa cells in 50 μ l PBS were injected subcutaneously into the footpad of each mouse (n = 6 for both groups). Cells from the experimental and control groups were inoculated under the right and left footpads of each mouse, respectively. After 8 weeks, the popliteal lymph nodes were excised.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Procathepsin L (CTSL) 45 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name KGP94 Clinical trial [3]
Synonyms
CHEMBL1269632; BDBM50330030
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 25234575
TTD: D0X6QL
 Compound Name PMID27998201-Compound-1 Patented [4]
MOA Inhibitor
External Link
CID: 826236
TTD: D0J0WG
 Compound Name PMID27998201-Compound-19 Patented [4]
MOA Inhibitor
Activity IC50 = 3.6 nM
External Link
CID: 100951597
TTD: D0ZN3M
 Compound Name Phenylalanine derivative 1 Patented [4]
Synonyms
PMID27998201-Compound-21
    Click to Show/Hide
MOA Inhibitor
External Link
TTD: D01MKD
 Compound Name PMID27998201-Compound-7 Patented [4]
MOA Inhibitor
Activity IC50 = 0.6 nM
External Link
CID: 73294953
TTD: D0JD5W
 Compound Name PMID27998201-Compound-6 Patented [4]
MOA Inhibitor
Activity IC50 = 8.06 nM
External Link
TTD: D0X1AF
 Compound Name PMID27998201-Compound-17 Patented [4]
MOA Inhibitor
Activity IC50 = 56 nM
External Link
TTD: D06XTA
 Compound Name PMID27998201-Compound-9 Patented [4]
MOA Inhibitor
Activity Ki = 0.0031 nM
External Link
CID: 78108715
TTD: D04VGR
 Compound Name PMID25399719-Compound-17 Patented [5]
MOA Inhibitor
Activity Ki = 66000 nM
External Link
TTD: D06LLT
 Compound Name PMID27998201-Compound-5 Patented [4]
MOA Inhibitor
Activity Ki < 100 nM
External Link
CID: 46202117
TTD: D05OIU
 Compound Name PMID27998201-Compound-12 Patented [4]
MOA Inhibitor
Activity IC50 < 0.25 nM
External Link
TTD: D06XCD
 Compound Name CLIK-148 Preclinical [6]
Synonyms
SCHEMBL7207304
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 9801663
TTD: DW24LQ
 Compound Name CLIK-181 Preclinical [7]
Synonyms
J3.633.044I
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 132504749
TTD: DYU3I8
 Compound Name SD1002 Preclinical [7]
MOA Inhibitor
External Link
TTD: DCZ16N
 Compound Name Z-Phe-Ala-diazomethylketone Preclinical [7]
Synonyms
71732-53-1; CHEMBL2179950; carbobenzoxycarbonyl-phenylalanyl-alaninyldiazomethane; ZPAD; Z-FA-DMK; SCHEMBL9364460; SCHEMBL17747846; SCHEMBL17747847; ZINC4899534; BDBM50400264; MFCD00077029; (Z,3S)-1-diazonio-3-[[(2S)-3-phenyl-2-(phenylmethoxycarbonylamino)propanoyl]amino]but-1-en-2-olate; Q27278127; benzyl (S)-1-((S)-4-diazo-3-oxobutan-2-ylamino)-1-oxo-3-phenylpropan-2-ylcarbamate; benzyl N-[(2S)-1-[[(2S)-4-diazo-3-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 155664
TTD: DM69TL
 Compound Name SD1003 Preclinical [7]
MOA Inhibitor
External Link
TTD: DSM03D
 Compound Name L-006235-1 Preclinical [8]
Synonyms
294623-49-7; L 006235; CHEMBL426819; N-(1-((cyanomethyl)carbamoyl)cyclohexyl)-4-(2-(4-methylpiperazin-1-yl)thiazol-4-yl)benzamide; L006235; N-[1-[[(Cyanomethyl)amino]carbonyl]cyclohexyl]-4-[2-(4-methyl-1-piperazinyl)-4-thiazolyl]benzamide; SCHEMBL6183485; CTK8E9371; BDBM19854; DTXSID90432735; MolPort-023-276-653; BCP28510; ZINC3993799; AKOS024457410; basic piperazine-containing compound, 1; NCGC00371088-01; RT-013466; CRA-013783/L-006235; J-017526; L-006235; L-006,235
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 340 nM
External Link
CID: 9912381
TTD: D0Z0PR
 Compound Name [(3-Bromophenyl)-m-tolyl-ketone]thiosemicarbazone Investigative [9]
Synonyms
CHEMBL602092
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 224 nM
External Link
CID: 46232847
TTD: D00VAN
 Compound Name Bis(3-bromophenyl)(5-hydroxy)thiosemicarbazone Investigative [3]
Synonyms
CHEMBL1271493
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 232.4 nM
External Link
CID: 52942034
TTD: D01CSE
 Compound Name CAA0225 Investigative [10]
Synonyms
CAA-0225; GTPL6532; (2S,3S)-2-N-[(1S)-1-(benzylcarbamoyl)-2-phenylethyl]-3-N-[2-(4-hydroxyphenyl)ethyl]oxirane-2,3-dicarboxamide
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 50909779
TTD: D01YTS
 Compound Name BIPHENYL-4-YL-ACETALDEHYDE Investigative [11]
Synonyms
2-([1,1'-biphenyl]-4-yl)acetaldehyde; 61502-90-7; 2-(4-phenylphenyl)acetaldehyde; 4-biphenylacetaldehyde; 2-{[1,1'-biphenyl]-4-yl}acetaldehyde; AC1MRDQD; (biphenyl-4-yl)ethanone; SCHEMBL850634; 2-(biphenyl-4-yl)acetaldehyde; CTK2D8632; DTXSID30392980; OIDMZCMVYZLDLI-UHFFFAOYSA-N; MolPort-020-915-677; [1,1'-Biphenyl]-4-acetaldehyde; ZINC2581188; AKOS006278290; AS-49992; BP4
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 3491292
TTD: D02RWL
 Compound Name Peptide alpha-keto-beta-aldehyde-based inhibitors Investigative [12]
Synonyms
CHEMBL48605; BDBM50090643; (3S)-3-[(Ac-L-Leu-L-Leu-)Amino]-6-guanidino-2-oxohexanal; (S)-2-Acetylamino-4-methyl-pentanoic acid {(S)-1-[(S)-4-guanidino-1-(2-oxo-acetyl)-butylcarbamoyl]-3-methyl-butyl}-amide
    Click to Show/Hide
MOA Inhibitor
Activity Ki = 970 nM
External Link
CID: 10095492
TTD: D08TWJ
 Compound Name (3-Bromobenzoylpyridine)thiosemicarbazone Investigative [3]
Synonyms
CHEMBL1269715
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 1000 nM
External Link
CID: 52940642
TTD: D09NBP
 Compound Name 1-(1,3-diphenylpropylidene)thiosemicarbazide Investigative [13]
Synonyms
CHEMBL429858; BDBM50377591
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 910 nM
External Link
CID: 44449925
TTD: D0B4JS
 Compound Name 6-(benzylamino)-9-butyl-9H-purine-2-carbonitrile Investigative [14]
Synonyms
Compound 3{8,12}; CHEMBL255079
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 4380 nM
External Link
CID: 24777047
TTD: D0J7OM
 Compound Name [2-Phenylacetophenone]thiosemicarbazone Investigative [3]
Synonyms
CHEMBL1269810
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 5410 nM
External Link
CID: 52945875
TTD: D0LL1F
 Compound Name Bis(3-Fluorophenyl)-ketone]thiosemicarbazone Investigative [9]
Synonyms
CHEMBL602732
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 4870 nM
External Link
CID: 46232386
TTD: D0M3AP
 Compound Name 9-benzyl-6-(benzylamino)-9H-purine-2-carbonitrile Investigative [14]
Synonyms
Compound 3{8,17}; CHEMBL400454
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 12220 nM
External Link
CID: 24778186
TTD: D0MD6D
 Compound Name 1-(phenyl(p-tolyl)methylene)thiosemicarbazide Investigative [13]
Synonyms
CHEMBL402465
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 1020 nM
External Link
CID: 15722900
TTD: D03JYN
 Compound Name Bis(3-bromophenyl)(4-hydroxy)thiosemicarbazone Investigative [3]
MOA Inhibitor
Activity IC50 = 126.1 nM
External Link
CID: 136002679
TTD: D04DFX
 Compound Name [(3-Bromophenyl)-p-tolyl-ketone]thiosemicarbazone Investigative [9]
Synonyms
CHEMBL590497
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 2160 nM
External Link
CID: 46232967
TTD: D0B2JC
 Compound Name N-(tert-butoxycarbonyl)-tyrosyl-glycine-nitrile Investigative [15]
Synonyms
dipeptide-derived nitrile, 23; CHEMBL371893; BDBM20102; tert-butyl N-[(1S)-1-[(cyanomethyl)carbamoyl]-2-(4-hydroxyphenyl)ethyl]carbamate
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 11551481
TTD: D0JF8D
 Compound Name (S)-tert-butyl 1-oxohexan-2-ylcarbamate Investigative [16]
Synonyms
CHEMBL96875; ((S)-1-Formyl-pentyl)-carbamic acid tert-butyl ester; BML-244; Carbamic acid, [(1S)-1-formylpentyl]-, 1,1-dimethylethyl ester; SCHEMBL3285479; CTK0G6629; OBMGXPJNZKYOQY-VIFPVBQESA-N; ZINC13588585; BDBM50137790; AKOS030572335; tert-butyl(1S)-1-formylpentylcarbamate; CCG-207873; 2(S)-(tert-Butoxycarbonylamino)hexanal; tert-butyl (1S)-1-formylpentylcarbamate; (2S)-2-(tert-Butoxycarbonylamino)hexanal; (S)-2-(tert-butoxycarbonylamino)-5-methylpentanal
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 8900 nM
External Link
CID: 10420833
TTD: D0T7QF
 Compound Name N-(tert-butoxycarbonyl)-isoleucyl-glycine-nitrile Investigative [15]
Synonyms
dipeptide-derived nitrile, 9; CHEMBL197113; BDBM20088; tert-butyl N-[(1S,2R)-1-[(cyanomethyl)carbamoyl]-2-methylbutyl]carbamate
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 23648531
TTD: D01YNC
 Compound Name N-(tert-butoxycarbonyl)-valyl-glycine-nitrile Investigative [15]
Synonyms
N-(tert-butoxycarbonyl)-L-valyl-glycine-nitrile; 191033-03-1; dipeptide-derived nitrile, 5; CHEMBL200004; BDBM20085; tert-butyl N-[(1S)-1-[(cyanomethyl)carbamoyl]-2-methylpropyl]carbamate
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 14774521
TTD: D06VIP
 Compound Name N-(tert-butoxycarbonyl)-norleucyl-glycine-nitrile Investigative [15]
Synonyms
dipeptide-derived nitrile, 13; CHEMBL383584; BDBM20092; tert-butyl N-[(1S)-1-[(cyanomethyl)carbamoyl]pentyl]carbamate
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 11637576
TTD: D07FLB
 Compound Name N-(4-phenylbenzoyl)-phenylalanyl-glycine-nitrile Investigative [15]
Synonyms
phenylalanine derivative, 44; CHEMBL200235; BDBM20120
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 11696652
TTD: D07RSA
 Compound Name N-(tert-butoxycarbonyl)-leucyl-glycine-nitrile Investigative [15]
Synonyms
dipeptide-derived nitrile, 7; CHEMBL200160; SCHEMBL6257676; BDBM20087; tert-butyl N-[(1S)-1-[(cyanomethyl)carbamoyl]-3-methylbutyl]carbamate
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 11492732
TTD: D09AHN
 Compound Name N-acetyl-phenylalanyl-glycine-nitrile Investigative [15]
Synonyms
phenylalanine derivative, 42; CHEMBL197181; SCHEMBL15634553; BDBM20118; ITHLBMBCVIAAIX-LBPRGKRZSA-N; ZINC13676602; (N-acetyl-l-phenylalanyl)aminoacetonitrile; SR-03000002938; SR-03000002938-1; (S)-2-Acetamido-N-(cyanomethyl)-3-phenylpropanamide
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 11086036
TTD: D0A8OV
 Compound Name N-(benzyloxycarbonyl)-leucyl-glycine-nitrile Investigative [15]
Synonyms
dipeptidyl nitrile, 1; Cbz-Leu-NH-CH2-CN; JMC487688 Compound 8; CHEMBL200161; SCHEMBL6183068; BDBM19768; UFXQLUZNMRVTPU-AWEZNQCLSA-N; 2-[(Z-L-Leu-)Amino]ethanenitrile; benzyl (S)-1-cyanomethylcarbamoyl-3-methylbutylcarbamate; benzyl N-[(1S)-1-[(cyanomethyl)carbamoyl]-3-methylbutyl]carbamate
    Click to Show/Hide
MOA Inhibitor
Activity Ki = 2790 nM
External Link
CID: 11702208
TTD: D0G8OD
 Compound Name N-benzoyl-phenylalanyl-glycine-nitrile Investigative [15]
Synonyms
phenylalanine derivative, 43; SCHEMBL5517755; CHEMBL371466; BDBM20119
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 11702265
TTD: D0JN8Q
 Compound Name N-(tert-butoxycarbonyl)-methionyl-glycine-nitrile Investigative [15]
Synonyms
dipeptide-derived nitrile, 12; CHEMBL381847; BDBM20091; tert-butyl N-[(1S)-1-[(cyanomethyl)carbamoyl]-3-(methylsulfanyl)propyl]carbamate
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 11709032
TTD: D0U0XG
 Compound Name (S)-1-benzylcyclopentyl 1-oxohexan-2-ylcarbamate Investigative [16]
Synonyms
CHEMBL117658; 1-(PHENYLMETHYL)CYCLOPENTYL[(1S)-1-FORMYLPENTYL]CARBAMATE; 2auz; BDBM50148292; DB07593; 1-benzylcyclopentyl [(1S)-1-formylpentyl]carbamate; 1-benzylcyclopentyl N-[(2S)-1-oxohexan-2-yl]carbamate; ((S)-1-Formyl-pentyl)-carbamic acid 1-benzyl-cyclopentyl ester
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 2000 nM
External Link
CID: 10062714
TTD: D0VE0F
DrugBank: DB07593
 Compound Name Cysteinesulfonic Acid Investigative [17]
Synonyms
Cysteic Acid; 3-Sulfoalanine; 2-amino-3-sulfopropanoic acid; DL-CYSTEIC ACID; 13100-82-8; beta-Sulfoalanine; Alanine, 3-sulfo-; Cysteinic acid; Cysteric acid; Cipteic acid; Cepteic acid; 3024-83-7; CHEBI:21260; C-9550; 2-amino-3-sulfopropanoate; cysteinsaure; Cepteate; Cysterate; Cipteate; Cysteinesulfonate; NSC 254030; (2R)-2-amino-3-sulfo-propanoic acid; L-Cysteic acid, 8; ACMC-209kii; 3-Sulfoalanine, (L)-; 2-Amino-3-sulfopropionate; AC1L19KC; SCHEMBL44030; CHEMBL1171434; 2-amino-3-sulfopro-panoic acid; BDBM85473; CTK8G7889
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 72886
TTD: D05AMX
DrugBank: DB03661
 Compound Name L-873724 Investigative [18]
Synonyms
UNII-29250PP3ON; 603139-12-4; CHEMBL437501; 29250PP3ON; (2S)-N-(cyanomethyl)-4-methyl-2-[[(1S)-2,2,2-trifluoro-1-[4'-(methylsulfonyl)[1,1'-biphenyl]-4-yl]ethyl]amino]Pentanamide; (2S)-N-(cyanomethyl)-4-methyl-2-[[(1S)-2,2,2-trifluoro-1-[4-(4-methylsulfonylphenyl)phenyl]ethyl]amino]pentanamide; VYFDSJLOCIGIKP-SFTDATJTSA-N; GTPL7860; SCHEMBL2157182; BDBM19489; (+)-L-873724; ZINC34802820; CS-6814; HY-50887; Pentanamide, N-(cyanomethyl)-4-methyl-2-(((1S)-2,2,2-trifluoro-1-(4'-(methylsulfonyl)(1,1'-biphenyl)-4-yl)eth
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 1221 nM
External Link
CID: 9913088
TTD: D0D0LD
WD repeat-containing protein 5 (WDR5) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name OICR-9429 Investigative [19]
Synonyms
1801787-56-3; OICR9429; CHEMBL3798846; N-(4-(4-Methylpiperazin-1-Yl)-3'-(Morpholinomethyl)-[1,1'-Biphenyl]-3-Yl)-6-Oxo-4-(Trifluoromethyl)-1,6-Dihydropyridine-3-Carboxamide; N-[2-(4-methylpiperazin-1-yl)-5-[3-(morpholin-4-ylmethyl)phenyl]phenyl]-6-oxo-4-(trifluoromethyl)-1,6-dihydropyridine-3-carboxamide; GTPL8231; OICR 9429; MolPort-039-101-294; EX-A2417; BCP18185; BDBM50164794; s7833; AKOS025147341; ZINC231558892; SB19642; CS-5776; NCGC00371263-02; AK468854; HY-16993; J3.618.049H
    Click to Show/Hide
MOA Antagonist
External Link
CID: 91623360
TTD: D0XI3W
References
Ref 1 METTL3 potentiates progression of cervical cancer by suppressing ER stress via regulating m6A modification of TXNDC5 mRNA. Oncogene. 2022 Sep;41(39):4420-4432. doi: 10.1038/s41388-022-02435-2. Epub 2022 Aug 20.
Ref 2 Methyltransferase-like 3 promotes cervical cancer metastasis by enhancing cathepsin L mRNA stability in an N6-methyladenosine-dependent manner. Cancer Sci. 2023 Mar;114(3):837-854. doi: 10.1111/cas.15658. Epub 2023 Jan 2.
Ref 3 Functionalized benzophenone, thiophene, pyridine, and fluorene thiosemicarbazone derivatives as inhibitors of cathepsin L. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6610-5. doi: 10.1016/j.bmcl.2010.09.026. Epub 2010 Sep 15.
Ref 4 Cathepsin B and L inhibitors: a patent review (2010 - present). Expert Opin Ther Pat. 2017 Jun;27(6):643-656. doi: 10.1080/13543776.2017.1272572. Epub 2016 Dec 23.
Ref 5 An updated patent review of calpain inhibitors (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):17-31.
Ref 6 Structure-based development of specific inhibitors for individual cathepsins and their medical applications. Proc Jpn Acad Ser B Phys Biol Sci. 2011;87(2):29-39.
Ref 7 Lysosomes as a therapeutic target. Nat Rev Drug Discov. 2019 Dec;18(12):923-948. doi: 10.1038/s41573-019-0036-1. Epub 2019 Sep 2.
Ref 8 Lysosomotropism of basic cathepsin K inhibitors contributes to increased cellular potencies against off-target cathepsins and reduced functional selectivity. J Med Chem. 2005 Dec 1;48(24):7535-43. doi: 10.1021/jm0504961.
Ref 9 Design, synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin L inhibitors. Bioorg Med Chem Lett. 2010 Feb 15;20(4):1415-9. doi: 10.1016/j.bmcl.2009.12.090. Epub 2010 Jan 6.
Ref 10 Characterization of CAA0225, a novel inhibitor specific for cathepsin L, as a probe for autophagic proteolysis. Biol Pharm Bull. 2009 Mar;32(3):475-9.
Ref 11 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. doi: 10.1093/nar/28.1.235.
Ref 12 Synthesis and kinetic evaluation of peptide alpha-keto-beta-aldehyde-based inhibitors of trypsin-like serine proteases. J Pharm Pharmacol. 2001 Apr;53(4):473-80.
Ref 13 Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB. Bioorg Med Chem Lett. 2008 May 1;18(9):2883-5. doi: 10.1016/j.bmcl.2008.03.083. Epub 2008 Apr 8.
Ref 14 Development of potent purine-derived nitrile inhibitors of the trypanosomal protease TbcatB. J Med Chem. 2008 Feb 14;51(3):545-52.
Ref 15 Interaction of papain-like cysteine proteases with dipeptide-derived nitriles. J Med Chem. 2005 Dec 1;48(24):7688-707.
Ref 16 Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde inhibitors?. Bioorg Med Chem Lett. 2006 Feb 15;16(4):978-83. doi: 10.1016/j.bmcl.2005.10.108. Epub 2005 Nov 15.
Ref 17 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 18 The identification of potent, selective, and bioavailable cathepsin S inhibitors. Bioorg Med Chem Lett. 2007 Sep 1;17(17):4929-33. doi: 10.1016/j.bmcl.2007.06.023. Epub 2007 Jun 10.
Ref 19 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2831).