Relacatib (SB-462795) is a novel, potent, and orally active inhibitor of human cathepsins K, L, and V with K_i values of 41 pM, 68 pM, and 53 pM, respectively. Relacatib inhibits endogenous cathepsin K in situ in human osteoclasts and human osteoclast-mediated bone resorption with IC₅₀ values of 45 nM and 70 nM, respectively. Relacatib inhibits bone resorption in vitro in human tissue as well as in cynomolgus monkeys in vivo^[1][2].

Relacatib are incubated with human osteoclastoma-derived osteoclasts seeded onto bovine cortical bone slices in vitro biological activity, it shows inhibitory potency with K_i values of 0.041 nM, 0.068 nM,0.063 nM,1.6 nM,and 13 nM against human cathepsin K, cathepsin L, cathepsin V, cathepsin S and cathepsin B, respectively in the assay^[1].
Relacatib is against Monkey cathepsin K, cathepsin L,cathepsin V and cathepsin B with K_i values of 0.041 nM, 0.28 nM, 0.72 nM and 11nM, respectively. Relacatib is against mouse cathepsin L and rat cathepsin L with K_i values of 0.20 nM and 0.17 nM, respectively^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Relacatib (1-2 mg/kg 0.5 h intravenous infusion; 2-4 mg/kg oral bolus gavage) exhibits T_1/2, CL or V_dss with 109 mins, 19.5 mL/min/kg, or 1.86 L/kg in male Sprague-Dawley rats and 168 mins, 11.7 mL/min/kg, and 1.79 L/kg in monkeys, respectively in a PK iv/po crossover studies. The oral bioavailability of Relacatib is 28% in the monkey and 89.4% in the rats^[1].
SB-462795 (subcutaneous injection; 12 mg/kg; blood sample is drawn 1.5, 4, 24, 48, and 72 h post dose administration) significantly inhibits resorption as assessed by two markers of bone resorption,the N- (NTx) and C-telopeptides (CTx) of type I collagen measured in serum. SB-462795 does not exhibit difference of serum osteocalcin (a biomarker of osteoblast activity) between SB-462795 and vehicle treated animalsexcept for the 48 h time point where a significant reduction (42% lower than baseline vs. 18% lower than baseline with vehicle treatment)^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

540.63

C₂₇H₃₂N₄O₆S

362505-84-8

固體

White to off-white

Room temperature in continental US; may vary elsewhere.

• [1]. Dennis S Yamashita, et al. Structure Activity Relationships of 5-, 6-, and 7-methyl-substituted azepan-3-one Cathepsin K Inhibitors.J Med Chem  [Content Brief]

  [2]. S Kumar, et al.A Highly Potent Inhibitor of Cathepsin K (Relacatib) Reduces Biomarkers of Bone Resorption Both in Vitro and in an Acute Model of Elevated Bone Turnover in Vivo in Monkeys.Bone. 2007 Jan;40(1):122-31.  [Content Brief]