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SID 26681509

Names

[ CAS No. ]:
958772-66-2

[ Name ]:
SID 26681509

[Synonym ]:
Sibutramina [Spanish]
Medaria
N,N-dimethyl-1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutylamine
Sibutramina
S-[2-[(2-ethylphenyl)amino]-2-oxoethyl] [2-[(2S)-3-(1H-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]hydrazinyl]methanethioate
Sibutraminum
Reductil
N-{1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}-N,N-dimethylamine
Sibutraminum [Latin]
Butramin
Meridia
sibutramine

Biological Activity

[Description]:

SID 26681509 is a potent, reversible, competitive, and selective inhibitor of human cathepsin L with an IC50 of 56 nM. SID 26681509 inhibits in vitro propagation of malaria parasite Plasmodium falciparum and inhibits Leishmania major with IC50s of 15.4 μM and 12.5 μM, respectively. SID 26681509 shows no inhibitory activity against cathepsin G[1].

[Related Catalog]:

Research Areas >> Cancer
Research Areas >> Infection
Signaling Pathways >> Metabolic Enzyme/Protease >> Cathepsin

[Target]

IC50: 56 nM (Human cathepsin L), 15.4 μM (Plasmodium falciparum), 12.5 μM (Leishmania major)[1]


[In Vitro]

After a 4 hr preincubation with cathepsin L, SID 26681509 becomes more potent, demonstrating an IC50 of 1.0 nM. SID 26681509 is determined to be a slow-binding and slowly reversible competitive inhibitor. Through a transient kinetic analysis for single-step reversibility, inhibition rate constants are kon = 24,000 M-1s-1 and koff = 2.2 × 10-5 s-1 (Ki = 0.89 nM). Molecular docking studies are undertaken using the experimentally-derived X-ray crystal structure of papain/CLIK-148[1]. SID 26681509 inhibits papain and cathepsins B, K, S, and V with IC50 values determined after one hour ranging from 618 nM to 8.442 μM. SID 26681509 shows no inhibitory activity against the serine protease cathepsin G[1].

[In Vivo]

SID 26681509 treatment significantly improves survival in murine models of sepsis and reduces liver damage following warm liver ischemia/reperfusion (I/R) models[2].

[References]

[1]. Shah PP, et al. Kinetic characterization and molecular docking of a novel, potent, and selective slow-binding inhibitor of human cathepsin L. Mol Pharmacol. 2008 Jul;74(1):34-41.

[2]. Pribis JP, et al. The HIV Protease Inhibitor Saquinavir Inhibits HMGB1-Driven Inflammation by Targeting the Interaction of Cathepsin V with TLR4/MyD88. Mol Med. 2015 Dec;21(1):749-757.

Chemical & Physical Properties

[ Molecular Formula ]:
C27H33N5O5S

[ Molecular Weight ]:
539.64600

[ Exact Mass ]:
539.22000

[ PSA ]:
180.68000

[ LogP ]:
6.17740

Safety Information

[ Hazard Codes ]:
Xi

Synthetic Route

Click to get detail synthetic route

Related Compounds