294623-49-7 Usage
Description
N-[1-[[(Cyanomethyl)amino]carbonyl]cyclohexyl]-4-[2-(4-methyl-1-piperazinyl)-4-thiazolyl]benzamide, also known as L 006235, is a compound with a complex chemical structure. It is a cathepsin K inhibitor, which means it has the ability to selectively inhibit the activity of cathepsin K enzyme, an important target for various therapeutic applications.
Uses
Used in Pharmaceutical Industry:
L 006235 is used as a cathepsin K inhibitor for the treatment of conditions related to the overactivity of cathepsin K enzyme. Its high selectivity against other lysosomal/endosomal antitargets such as cathepsin B, L, and S makes it a promising candidate for targeted therapies with minimal side effects.
Used in Orthopedic Applications:
In the orthopedic field, L 006235 is used to inhibit cathepsin K, which plays a role in bone resorption. By inhibiting this enzyme, L 006235 can help in the treatment of conditions characterized by excessive bone breakdown, such as osteoporosis.
Used in Research and Development:
L 006235 is also used in research and development for studying the role of cathepsin K in various biological processes and disease mechanisms. Its high selectivity makes it a valuable tool for understanding the enzyme's function and potential therapeutic targets.
Biological Activity
l-006235 is a potent and selective inhibitor of cathepsin k.
in vitro
after dilution of l-006235 to 0.05 nm, the cathepsin k enzyme activity was initially inhibited, but slowly recovered with a first-order rate constant of 0.023 s-1. the final steady-state enzyme activity was 80-90% that of control, suggesting the complete reversibility of the l-006235-cathepsin k complex. l-006235 was found to be not a substrate for the nitrilase activity of cat k [1].
in vivo
l-006235 was orally bioavailable in rats, with a terminal half-life of over 3 h. l-006235 was orally dosed in ovariectomized rhesus monkeys once per day for 7 days. results showed that collagen breakdown products were dose-dependently reduced by up to 76%. plasma concentrations of l-006235 above the bone resorption ic50 after 24 h indicated a correlation between functional cellular and in vivo assays. these findings suggested that the inhibition of collagen breakdown by cathepsin k inhibitors, such as l-006235, might be useful in osteoporosis and other indications involving bone resorption [1].
IC 50
0.25 nm
references
[1] palmer jt,bryant c,wang dx et al. design and synthesis of tri-ring p3 benzamide-containing aminonitriles as potent, selective, orally effective inhibitors of cathepsin k. j med chem.2005 dec 1;48(24):7520-34.
Check Digit Verification of cas no
The CAS Registry Mumber 294623-49-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,9,4,6,2 and 3 respectively; the second part has 2 digits, 4 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 294623-49:
(8*2)+(7*9)+(6*4)+(5*6)+(4*2)+(3*3)+(2*4)+(1*9)=167
167 % 10 = 7
So 294623-49-7 is a valid CAS Registry Number.
294623-49-7Relevant articles and documents
Design and synthesis of tri-ring P3 benzamide-containing aminonitriles as potent, selective, orally effective inhibitors of cathepsin K
Palmer, James T.,Bryant, Clifford,Wang, Dan-Xiong,Davis, Dana E.,Setti, Eduardo L.,Rydzewski, Robert M.,Venkatraman, Shankar,Tian, Zong-Qiang,Burrill, Leland C.,Mendonca, Rohan V.,Springman, Eric,McCarter, John,Chung, Tobee,Cheung, Harry,Janc, James W.,McGrath, Mary,Somoza, John R.,Enriquez, Philip,Yu, Z. Walter,Strickley, Robert M.,Liu, Liang,Venuti, Michael C.,Percival, M. David,Falgueyret, Jean-Pierre,Prasit, Peppi,Oballa, Renata,Riendeau, Denis,Young, Robert N.,Wesolowski, Gregg,Rodan, Sevgi B.,Johnson, Colena,Kimmel, Donald B.,Rodan, Gideon
, p. 7520 - 7534 (2007/10/03)
We have prepared a series of achiral aminoacetonitriles, bearing tri-ring benzamide moieties and an aminocyclohexanecarboxylate residue at P2. This combination of binding elements resulted in sub-250 pM, reversible, selective, and orally bioavailable cathepsin K inhibitors. Lead compounds displayed single digit nanomolar inhibition in vitro (of rabbit osteoclast-mediated degradation of bovine bone). The best compound in this series, 39n (CRA-013783/L-006235), was orally bioavailable in rats, with a terminal half-life of over 3 h. 39n was dosed orally in ovariectomized rhesus monkeys once per day for 7 days. Collagen breakdown products were reduced by up to 76% dose-dependently. Plasma concentrations of 39n above the bone resorption IC50 after 24 h indicated a correlation between functional cellular and in vivo assays. Inhibition of collagen breakdown by cathepsin K inhibitors suggests this mechanism of action may be useful in osteoporosis and other indications involving bone resorption.
