Delving into the Latest Updates on Balicatib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

CTSK

Action

inhibitors

Mechanism

CTSK inhibitors(Cathepsin K inhibitors)

Therapeutic Areas

Eye Diseases

Active Indication

Glaucoma, Open-Angle

Inactive Indication

Osteoarthritis, KneeOsteoporosis

Originator Organization

Novartis Pharma AG

Active Organization

The Indiana University School of Medicine

Inactive Organization

Novartis Pharmaceuticals Corp.

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC23H33N5O2

InChIKeyLLCRBOWRJOUJAE-UHFFFAOYSA-N

CAS Registry354813-19-7

A 2-year extension to study 2203, partially randomized, double-blind, placebo-controlled in the first year and open label in the second year, to assessthe safety of the dose of AAE581 selected for phase III development in postmenopausal osteoporosis, and the offset of effect on biomarkers and BMD - 2203E1

Start Date19 Apr 2005

Sponsor / Collaborator

Novartis Pharma Services AG

100 Clinical Results associated with Balicatib

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100 Translational Medicine associated with Balicatib

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100 Patents (Medical) associated with Balicatib

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34

Literatures (Medical) associated with Balicatib

01 Oct 2024·iScience

Efficacy of a cysteine protease inhibitor compared with enalapril in murine heart failure models

Article

Author: Barrabés, Jose A ; Ferreira-González, Ignacio ; Song, Long-Sheng ; Aluja, David ; Benito, Begoña ; Delgado-Tomás, Sara ; Barrabés, Jose A. ; Rodríguez-Sinovas, Antonio ; Wang, Jinxi ; Ruiz-Meana, Marisol ; Miró-Casas, Elisabet ; Inserte, Javier

Cysteine proteases calpains contribute to heart failure (HF), but it remains unknown whether their inhibition provides any benefit compared to standard pharmacological treatment for HF. Here, we characterize the pharmacological properties of NPO-2270 (NPO) as a potent inhibitor of cysteine proteases. Then, we describe that acute administration of NPO in rodent models of transient ischemia at the time of reperfusion reduces myocardial infarction, while its chronic oral administration attenuates adverse remodeling and cardiac dysfunction induced by ischemic and non-ischemic pathological stimuli more effectively than enalapril when given at the same dose. Finally, we provide evidence showing that the effects of NPO correlate with calpain inhibition and the preservation of the T-tubule morphology, due at least in part to reduced cleavage of the calpain substrate junctophilin-2. Together, our data highlight the potential of cysteine protease inhibition with NPO as a therapeutic strategy for the treatment of heart failure.

10 Nov 2023·Organic Letters

Electrochemical Synthesis of Unnatural Amino Acids via Anodic Decarboxylation of N-Acetylamino Malonic Acid Derivatives

Article

Author: Suna, Edgars ; Koleda, Olesja ; Prane, Katrina

Broad application of α,α-disubstituted cyclic amino acid derivatives in medicinal chemistry urges for analogue design with improved pharmacokinetic properties. Herein, we disclose an electrochemical approach toward unnatural THF- and THP-containing amino acid derivatives that relies on anodic decarboxylation-intramolecular etherification of inexpensive and readily available N-acetylamino malonic acid monoesters under Hofer-Moest reaction conditions. The decarboxylative cyclization proceeds under constant current conditions in an undivided cell in an aqueous medium without any added base. A successful bioisosteric replacement of the 1-aminocyclohexane-1-carboxylic acid subunit by the THP-containing amino acid scaffold in cathepsin K inhibitor balicatib helped to reduce lipophilicity while retaining low nanomolar enzyme inhibitory potency and comparable microsomal stability.

01 Oct 2023·Structural Chemistry

Binding mechanism of selective cathepsin K/S inhibition revealed from molecular simulations

Author: Ma, Yan ; Luan, Jiasi ; Hu, Baichun ; Xu, Feng ; Zhong, Qinyi ; Zhang, Fengjiao

Cathepsin K and S are two isoforms of cysteine protease with diverse biol. functions in the aspect of osteoporosis and autoimmune diseases.Accordingly, the homologous sequence and similar binding site features among CTSK/S may lead to unselective inhibition and side effects.To address such issue, various computational strategies were applied in the current study to explore the selectivity mechanism of CTSK/S inhibitors, including sequence alignment, mol. docking, MD simulations, MM/GBSA energy calculation, and so on.Our findings highlight the notable effects of CTSK residues Glu59 and Tyr67, as well as CTSS residue Asn67, on inhibition selectivity.Overall, this study provides an informative guideline for the rational design of CTSK/S selective inhibitors.

100 Deals associated with Balicatib

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12239

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Osteoarthritis, Knee	Phase 3	United States	Novartis Pharmaceuticals Corp.	01 Dec 2004
Osteoarthritis, Knee	Phase 3	Germany	Novartis Pharmaceuticals Corp.	01 Dec 2004
Osteoporosis	Phase 3	-	Novartis Pharmaceuticals Corp.	01 Feb 2004
Glaucoma, Open-Angle	Preclinical	United States	The Indiana University School of Medicine	01 Jun 2021