CA 074 TFA

Names

[ Name ]:
CA 074 TFA

[Synonym ]:
(L-3-trans-(Propylcarbamyl)oxirane-2-carbonyl)-L-isoleucyl-L-proline
L-TRANS-EPOXYSUCCINYL-ILE-PRO-OH PROPYLAMIDE
CATHEPSIN B INHIBITOR III
INHIBITOR FOR CATHEPSIN B

Biological Activity

[Description]:

CA-074 is a potent inhibitor of cathepsin B with a Ki of 2 to 5 nM.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> Cathepsin

Research Areas >> Neurological Disease

Research Areas >> Cancer

[Target]

Ki: 2 to 5 nM (Cathepsin B)[1]

[In Vitro]

CA-074 is a synthetic analogue of E-64, a natural peptidyl epoxide that irreversibly inhibits most known lysosomal cysteine proteinases, and is developed by means of rational drug design, exploiting the dipeptidylcarboxypeptidase activity of cathepsin B. CA-074 can be used to selectively inhibit cathepsin B within living cells, as long as the experimental conditions permit significant fluid-phase endocytosis of the drug[2]. CA-074 inhibits cathepsin B with a Ki of 2 to 5 nM, whereas the initial Kis for cathepsin H and L are about 40-200 μM. CA-074 exhibits 10000-30000 times greater inhibitory effects on purified rat cathepsin B than on cathepsin H and L[1].

[In Vivo]

Intraperitoneally injection of compound CA-074 into rats potently and selectively inhibits cathepsin B activity[1]. Intravenously administration of CA-074 immediately after the ischaemic insult saves 67% of CA1 neurons from delayed neuronal death on day 5 in eight monkeys undergoing 20 min brain ischaemia: the extent of inhibition is excellent in three of eight and good in five of eight monkeys[3].

[Animal admin]

Rats: Compound CA-074 or CA-030 or E-64 is injected intraperitoneally as a solution in saline containing DMSO. A dose of 8 mg/100 g body weight is injected. The rats are killed by a blow to the head 6 h after the injection, and their liver is perfused with saline, removed, weighed and chilled on ice. Samples of 4 g of liver are minced and homogenized. The homogenate is centrifuged at 800 xg for 15 min and the supernatant is centrifuged at 12000 xg for 30 min. The precipitate is suspended in 2 mL of 0.05 M acetate buffer, pH 5,0, and freeze-thawed for measurements of cathepsin B, H and L activities[1].

[References]

[1]. Towatari T, et al. Novel epoxysuccinyl peptides. A selective inhibitor of cathepsin B, in vivo. FEBS Lett. 1991 Mar 25;280(2):311-5.

[2]. Montaser M, et al. CA-074, but not its methyl ester CA-074Me, is a selective inhibitor of cathepsin B within living cells. Biol Chem. 2002 Jul-Aug;383(7-8):1305-8.

[3]. Yamashima T, et al. Inhibition of ischaemic hippocampal neuronal death in primates with cathepsin B inhibitor CA-074: a novel strategy for neuroprotection based on 'calpain-cathepsin hypothesis'. Eur J Neurosci. 1998 May;10(5):1723-33.

[Related Small Molecules]

Leupeptin hemisulfate salt | E-64 | PMSF | CA-074 methyl ester | LY 3000328 | Odanacatib(MK-0822) | VBY-825 | Balicatib | Cysteine Protease inhibitor | Papain | MK-0822 | Cathepsin Inhibitor 2 | E-64c | MIV-247

Chemical & Physical Properties

[ Density]:
1.267g/cm3

[ Boiling Point ]:
728.9ºC at 760mmHg

[ Molecular Formula ]:
C₁₈H₂₉N₃O₆

[ Molecular Weight ]:
383.43900

[ Flash Point ]:
394.7ºC

[ Exact Mass ]:
383.20600

[ PSA ]:
128.34000

[ LogP ]:
0.60620

[ Vapour Pressure ]:
0mmHg at 25°C

[ Index of Refraction ]:
1.539

[ Storage condition ]:
2-8℃

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

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Redox cycling compounds have been reported to cause false positive inhibition of proteases in drug discovery studies. This kind of false positives can lead to unusually high hit rates in high-throughp...

Structural basis for development of cathepsin B-specific noncovalent-type inhibitor: crystal structure of cathepsin B-E64c complex.

Biochim. Biophys. Acta 1597(2) , 244-51, (2002)

In order to elucidate the substrate specificity of the Sn subsites (n=1-3) of cathepsin B, its crystal structure inhibited by E64c [(+)-(2S,3S)-3-(1-[N-(3-methylbutyl)amino]-leucylcarbonyl)oxirane-2-c...