Home > Reagents > Inhibitors
Inhibitors
For details of calpain inhibitors, please see our recent review:
Ono Y et al (2016) Calpain research for drug discovery. Nat Rev Drug Discov 15:854-876.
Two-D chemical structures were drawn by MOE Ver. 2015.10.




Name, alias Structure
(click to show
the formula)
Composition formula (Mr) IC50
(nM)
Ki
(nM)
Maker PN pack-
age (mg)
Reference, note
Calpain Inhibitor I,
MG-101
Ac-L-Leu-L-Leu-L-norleucinal
file download
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C20H37N3O4 (383.53) C1: 310; C2: 160; papain: 4,500; MMP2: 2.2x104 C1: 86; C2: 192; papain: 2,200; CathB: 22; CathL: 0.5; trypsin: >5x105; proteasome: 6,000; thermolysin: >5x105; calcineurin /CaM: >2x105 Bachem AG N-1320 5, 25 1, 2, 3
A. G. Scientific
Inc.
P-1153 5, 25
Santa Cruz
Biotech. Inc.
SC-3089 0.5
MERCK/Calbiochem 208719 5, 25
MERCK/Calbiochem 208750 5 (in solution)
Sigma A6185 5, 25
Enzo/BioMol/Alexis BML-P120 (ALX-260-037) 5, 25
Calpain Inhibitor II Ac-L-Leu-L-Leu-L-methional
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C19H35N3O4S (401.57) C1: 250; C2: 140; papain: 3,600 CathB: 100; CathL: 0.6 Bachem AG N-1315 5, 25 1
A. G. Scientific
Inc.
C-1259 5, 25
MERCK/Calbiochem 208721 25
Enzo/BioMol/Alexis BML-PI100 (ALX-260-038) 5
Sigma A6060 5, 25
Calpain Inhibitor III, MDL-28170   Z-L-Val-L-
phenylalaninal

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C22H26N2O4 (382.46) C1: 7; CathB: 25; trypsin: >2x106; plasmin: 2.7x105; kalikrein: >5x106 Bachem AG N-1535 25, 100 4, 5, 6
MERCK/Calbiochem 208722 25
Enzo/BioMol BML-PI130 10, 50
Sigma M6690 25
Calpain Inhibitor IV Z-L-Leu-L-Leu
-L-Tyr-CH2F

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C30H40N3O6F
(557.66)
C11:
k2=2.9x104 M-1s-1; CathL:
k2=6.8x105 M-1s-1
MERCK/Calbiochem 208724 1 7, 8
A potent, cell-permeable, and irreversible inhibitor.
Kamiya Biomed. Co. (called "Calpain Inhibitor 1") AB-050 3
A. G. Scientific C-1551 1
"Calpain Inhibitor IV", MG-132 Z-L-Leu-L-Leu
-L-leucinal

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C26H41N3O5
(475.63)
C2: 1,200; 20S proteasome: 100 C2: 10; 20S proteasome: 6,900 Bachem AG N-1635 5, 25 9, 10, 11
Calpain Inhibitor V  morpholinoureidyl
-L-Val-L-
homophenylalanyl
-CH2F

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C21H30N3O4F
(407.49)
CathB: ~10; CathL: ~100 MERCK/Calbiochem 208726 1 12, 13
ca.70% inhibition of total cysteine protease activity from rat kidney by oral administration (10.0mg/kg)
Calpain Inhibitor VI, SJA6017 4-fluorophenyl
sulfonyl-L-Val
-L-leucinal

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C17H25N2O4SF
(372.46)
C1: 22; C2: 49; CathB: 6.9; CathL: 1.6; 20S proteasome: 105 MERCK/Calbiochem 208745 1, 5 14, 15, 16
Calpain Inhibitor X, AK275 Z-L-Leu-L-Abu
-CONH-C2H5

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C21H31N3O5
(405.50)
C1: 250; C2: 210; papain: 9.3x104; CathB: 2,400 Alfa Aesar J65826 1, 5 17, 18
A cell-permeable dipeptidyl α-ketoamide that acts as a potent, reversible, and active site inhibitor.
Calpain Inhibitor XI, AK295 Z-L-Leu-L-Abu
-CONH-(CH2)3
-morpholine

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C26H40N4O6
(504.63)
C1: 140; C2: 41; CathB: 6,900 MERCK/Calbiochem 208743 1, 5 18
A cell-permeable dipeptidyl α-ketoamide that acts as a potent, highly selective, reversible, and active site inhibitor.
Calpain Inhibitor XII Z-L-Leu-L
-norvaline
-CONH-CH2
-2-pyridyl

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C26H34N4O5
(482.58)
C1: 19; C2: 120; CathB: 750 Cayman Chemicals 14466 1, 5, 10 18
A cell-permeable compound that acts as a potent, selective, reversible, and active site inhibitor.
Santa Cruz sc-300318 1, 5
Alfa Aesar J64751 1, 5
Funakoshi 14466 1, 5, 10
"Calpain Inhibitor 2" Mu-Phe
-HPh-CH2F
C25H30O4N3F
(455)
    Kamiya
Biomed. Co.
AB-051 5 cross reactive to cathepsin L
Calpeptin   Z-L-Leu-L
-norleucinal

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C20H30N2O4
(362.47)
C1: 52; C2: 34; papain: 138; CathL: 138 Proteasome: 1.1x105 Immunoproteasome: 1,000 Enzo/BioMol/Alexis BML-PI101 (ALX-260-014) 10, 50 11, 19
MERCK/Calbiochem 03-34-0051  5, 25, 100
Z-Leu-Tyr-CH2Cl Z-Leu-Tyr
-CH2Cl
      Bachem AG N-1255 25, 100  
Z-Phe-Tyr-CHO Z-Phe-Tyr-CHO       Bachem AG N-1540 25, 100  
Z-Leu-Leu-CHO Z-Leu
-Leu-CHO
362.5 1200   BioMol BML-PI116 5, 25 100-fold selective for calpain over proteasome
Leupeptin  Ac-L-Leu-L
-Leu-L-argininal

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C20H38N6O4
(426.56)
C1: 351; C2: 176; papain: 1,500; CathB: 27 C1: 320; C2: 430; CathB: 6; trypsin: 35; plasmin: 3,400; kalikrein: 1.9x105 Bachem AG N-1000 5, 25, 100 1, 4, 14, 16, 20, 21
Peptide Inst. 4041, 4041-v 0.5 (vial), 25, 100, 1000
Sigma L2023 1, 5, 10, 25, 50, 100
E-64   [(2S,3S)-3
-carboxyoxirane-2
-carbonyl]-L-Leu-
(4-guanidinobutyl)
amide
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C15H27N5O5
(357.41)
C1: 1,000; C2: 2,600; papain: 290; CathB: 800 C11: 800 Bachem AG N-1645 5, 25 22, 23
BioMol ALX-260-007 (BML-PI105) 5, 25
MERCK/Calbiochem 324890 1, 5, 25
Peptide Inst. 4096, 4096-v 0.5 (vial), 25, 100, 1000
E-64-c   [(2S,3S)-3
-carboxyoxirane-2
-carbonyl]-L-Leu
-(3-methylbutyl)amide
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C15H26N2O5
(314.38)
C11: 1.5x104; papain: 4,400; CathB: 240; CathL: 90 C11: 960 Bachem AG N-1655 1, 5 23, 24, 25
Synthetic analog of E-64.
BioMol BML-PI106 1
Peptide Inst. 4320-v 5
Sigma E0514 1, 5
E-64-d, EST,
Loxistatin
[(2S,3S)-3-ethoxy
carbonyloxirane
-2-carbonyl]-L-Leu
-(3-methylbutyl)amide
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C17H30N2O5
(342.44)
    Bachem AG N-1650 1, 5 24
A cell-permeable, irreversible inhibitor of cysteine proteases. Similar to E-64 but devoid of charged groups. The inhibitory activity of EST has been attributed to E-64c, the free acid formed by hydrolysis of the ester in vivo.
MERCK/Calbiochem 330005 1
Peptide Inst. 4321-v 5
Sigma E8640 0.25, 1
PD150606 3-(4-iodophenyl)-2
-mercapto-(Z)-2
-propenoic acid

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C9H7O2SI
(306.12)
MMP2: 9,300 C1: 210; C2: 370; papain: 1.5x105; CathB: 1.3x105;
trypsin: 5x105; thermolysin: 2.0x105; calcineurin/CaM: 1.3x104
MERCK/Calbiochem 513022 5 2, 3
A cell-permeable, non-competitive, selective non-peptide inhibitor.
PD151746 3-(5-fluoro-
3-indolyl)-
2-mercapto-(Z)-
2-propenoic acid

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C11H8NO2SF
(237.25)
C1: 260; C2: 5,300; papain: 5x105; CathB: 2x105; trypsin: 5x105; thermolysin: 5x105; calcineurin/CaM: 8.5x104 MERCK/Calbiochem 513024 5 2
A cell-permeable, non-competitive, selective non-peptide inhibitor.
PD145305 2-Mercapto-3-
phenyl
propanonic acid
182.2     Santa Cruz sc-222131 5 Negative control for PD150606 and PD151746.
Calpastatin,
domain 1
134 aar 14,208.52     Takara 7316 3 50 and 15 nM of calpastatin domain 1 inhibits, respectively, 100% and 50% of the activity of 7.5 µg/ml calpain-1 [µ-calpain].
Ac-
Calpastatin
(184-210)
Ac-DPMSSTYIEE
LGKREVTIPP
KYRELLA-NH2
3177.67     Bachem AG H-4076 0.5, 1  
Calpain
inhibitor
peptide
(C-9181)
DPMSSTYIEE
LGKREVTIPP
KTRELLA
3136.56     Sigma C-9181 0.5  
AK269 Z-L-Leu-L-Phe
-CONH-C2H5

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C26H33N3O5
(467.57)
  C1: 200; C2: 39; CathB: 4.5x104; CathL: 6,000 -     17, 18
mCalp-I Z-L-Leu-L-Abu
-CONH-CH2
-C6H3-3,5
-(OCH3)2

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C28H37N3O7
(527.62)
C1: 2,300; C2: 22; CathB: 1,800 C1: 940; C2: 25; CathB: - -     18, 26
CEP-3122 CH3-SO2-D
-phenylmethyl
serine-L
-phenylalaninal

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C20H24N2O5S
(404.49)
C1: -; C2: -; papain: - C1: 8; C2: 5; papain: 32 -     27, 28
CEP-3453 HSO3 addition
of CEP-3122

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  C1: 8; CathB: 15 C1: -; CathB: - -     28
MDL104903 [1-[(5-hydroxy-
4-phenylmethyl
-3-oxazolidinyl)
carbonyl]-2-
ethylpropyl]
carbamic acid
phenylmethyl ester

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C23H28N2O5
(412.49)
C1: - C1: 33 -     29
BDA-410 (2S)-N-[(1S)-1-[(S)
-hydroxy(3-oxo
-2-phenyl-1-
cyclopropen-1
-yl)methyl]-2-
methylpropyl]-2-
benzenesulfonyl
amino-4-methyl
pentanamide

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C26H32N2O5S
(484.62)
C1: 21; C2: 21; papain: 400; CathB: 1.6x105 C1: 130; C2: 630; papain: -; CathB: -; thrombin, CathG, and proteasome: 1.0x105; CathD: 9.1x105 -     30, 31, 32
SJA7019 chloroacetic acid
N'-[6,7-dichloro
-4-(4-methoxy
phenyl)-3-oxo
-3,4-dihydro
quinoxalin
-2-yl]hydrazide

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C17H13N4O3Cl3
(427.67)
C1: 77; C2: 64; CathL: 1,500 C1: -; C2: -; papain: -; CathL: - -     33
SJA7029 chloroacetic acid
N'-(6,7-dichloro
-4-phenyl-3-oxo
-3,4-dihydro
quinoxalin
-2-yl)hydrazide

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C16H11N4O2Cl3
(397.65)
C1: 120; C2: 170; CathL: 4,200 C1: -; C2: -; papain: -; CathL: - -     33
SNJ1715 (2S)-4-methyl
-2-(3-phenyl
thioureido)-N-
[(3S)-tetrahydro
-2-hydroxy
-3-furanyl]
pentanamide

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C17H25N3O3S
(351.47)
C1: 86; C2: 190; CathL: 4,200; 20S proteasome: >105 C1: -; C2: - -     15
SNJ1757 (2S,5S)-5-benzyl
-6-hydroxy-2-(2
-methylpropyl)-3
-morpholinone

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C15H21NO3
(263.34)
C1: 700; C2: 930; CathB: >1x105 C1: -; C2: -: CathB: - -     16
SNJ1945 [(1S)-1-([((1S)-
1-benzyl-3-(cyclo
propylamino)
-2,3-dioxopropyl)
amino]carbonyl)
-3-methylbutyl]
carbamic acid
5-methoxy
-3-oxapentyl ester

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C25H37N3O7
(491.58)
C1: 170; C2: 99 C1: -; C2: - -     34
SNJ2008 [(1S)-1-[([(1S)
-1-benzyl-3-
(cyclopropyl
amino)-2,3-dioxo
propyl]amino)
carbonyl]-3-
methylbutyl]
carbamic acid
2-(pyridin-2-yl)
ethyl ester

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C27H34N4O5
(494.59)
C1: 29; C2: 17 C1: -; C2: - -     35, 36
A-705239, BSF 409425 N-(1-carbamoyl
-1-oxohex-1-yl)-2
-[E-2-(4-dimethyl
aminomethyl
phenyl)ethen-1-
yl]benzamide

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C25H31N3O3
(421.54)
C1: -; CathB: -; CathL: - C1: 13 ;CathB: 27; CathL: 22; proteasome: 4.0x105 -     37, 38
A-705253, BSF 419961, CAL 9961 N-(1-benzyl-2-
carbamoyl-2-
oxoethyl)-2-[E-
2-(4-diethylamino
methylphenyl)
ethen-1-yl]
benzamide

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C30H33N3O3
(483.61)
C1: -; CathB: -; CathL: - C1: 27 ;CathB: 62; CathL: 149; proteasome: 2.6x104 -     37, 38
BN 82270 phenothiazine-
L-Leu-2-hydroxy
tetrahydrofuran

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C25H29N3O5S
(483.59)
C1: >1,000; Cellular calpain inhibition: 1.3x104; Fe2+ induced lipid peroxidation in rat brain microsomes inhibition: 1.6x104 -     39, 40
Dual inhibitor for calpains (active after hydrolysis of the acetyl group) and lipid peroxidation.
C-101, Myodur L-aminocarnityl
succinyl-L
-Leu-L-argininal dichloride

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C23H47N7O6Cl2
(588.58)
spectrin breakdown (145 kDa): 3.7x104   -     41
C-201, Neurodur L-cysteyl-L-Leu
-L-argininal

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C15H30N6O6S
(422.51)
    -     42
No Ki or IC50 data.
CYLA diethyl acetal
of C-201

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C19H40N6O7S
(496.63)
    -     43
Active only after hydrolysis (=C-201).
GABAdur pregabalin-
L-Leu-
L-argininal

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C20H38N6O5
(442.56)
    -     44
No Ki or IC50 data.
Olesoxime, TRO19622 (3Z)-N-hydroxy
cholest-4-en
-3-imine

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C27H45NO
(399.66)
mitochondrial translocator protein 18 kDa and its ligand, PK11195, binding: 3~5x104 C1: **; C2: ** -     45, 46, 47
**Showing in vivo inhibitory activity.
Hypervalent organotellurium compound, RF19 No.11 or RF19
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C15H13OCl3Te
(443.23)
P. falciparum proteases: 200 CathB: 7,900; CathL: 9,400; CathS: 2.0x105; CathK: 3.8x105 -     48, 49
Macrocyclic aldehyde, CAT811 ((7S,10S,13S)
-7-formyl-10-
isobutyl-9,12-
dioxo-2-oxa-
8,11-diaza-
bicyclo[13.2.2]
nonadeca-
1(18),15(19),
16-trien-13-yl)
-carbamic acid benzyl ester

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C29H37N3O6
(523.63)

C1: 220; C2: 30; papain: >5x105; CathB: 70; pepsin and α-chymotrypsin: >5x105

-     50
Indole-containing 18-membered aldehyde (S)-N-[(S)-4-methyl-1
-oxopentan-2-yl]-2, 16
-dioxo-3,20-diazabicyclo
[15.2.1]icosa-l(19),17-diene
-4-carbox
amide

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C25H39N3O4
(445.60)

C1: 42; C2: 66; α-chymotrypsin: >2.5x105

-     51
α-helical peptide Ac-IPPKY
CELLC-NH2

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C64H96N12O14S2
(1321.67)

C1: 1x104; papain: >1x105; CathB: >1x105;CathL: 3.9x104

-     52
Dipeptidyl α,β-unsaturated ester (E)-ethyl-4-(2-(benzyl-oxycarbonyl-amino)-4-methyl pentanamido)-5-phenylpent-2-enoate
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C27H34N2O5
(466.58)
P. falciparum growth rate in human erythrocytes: 5x103; HeLa cell growth: 3.5x105   -     53
Macrocyclic β-turn peptide c*[PGALK]
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C30H54N8O6
(622.81)
C1: (~50%)***; C2: 1.7x104; papain: (~10%); CathL: (~100%) -     54
***showing relative values to inhibitory effect observed for C2 under the same condition.
Abbreviations:
Z: benzyloxycarbonyl, Mu: morphlinoureidyl, HPh: homophenylalanyl, Abu, α-aminobutylic acid residue; Ac, acetyl; C1, calpain-1; C2, calpain-2; C11, chicken calpain-11; CathB/H/L, cathepsin B/H/L.

Notes:
*k2 indicates a rate constant (M-1s-1) of a reaction, E+I->EI (E: enzyme, I: inhibitor).

References:
Notes for references:
1. The original report was by Saito, M., Higuchi, N., Kawaguchi, N., Tanaka, T. and Murachi, T. at the 4th FAOB Congress in Singapore, November 30, 1986 (Abstracts of Papers, p58).
12. This reference described synthesis and the effect of morpholinoureidyl-L-Leu-L-homophenylalanyl-CH2F (mu-L-hF-fmk, P34089), but not those of Val (mu-V-hF-fmk, i.e., CI-V). Since the described method can be applied to mu-V-hF-fmk (CI-V) and no other reference describing the synthesis of CI-V was found, this reference is cited here.
17,18. The AK275 was first synthesized as a diastereometric mixture (called CX275); however, since a later study56 showed that the L, L isomer has inhibitory activity, this active structure is shown here, and so are for other AK series inhibitors.
20. In the original report, leupeptin was shown to have DL-argininal; however, a later study55 showed that L-argininal, but not D-argininal, has a strong affinity to trypsin. Thus, the structure is shown as Ac-L-Leu-L-Leu-L-argininal.
33. The original report was by Inoue, J., Cui, Y.-S., Sakai, O., Nakamura, M., Yuen, P.-W., and Wang, K.K.W. (1999) α-Substituted hydrazides having calpain inhibitory activity, in Proceedings of the FASEB Summer Conference on Calpains, 1999 June 20–23, Breckenridge, CO.
41. This reference did not mention about the stereochemical analysis, and, thus, the structure is an estimate from those of L-carnitine and leupeptin.
42. This reference did not mention about the stereochemical analysis, and, thus, the structure is an estimate from those of L-cysteic acid and leupeptin.
44. This reference did not mention about the stereochemical analysis, and, thus, the structure is an estimate from those of pregabalin and leupeptin.

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