Delving into the Latest Updates on Balicatib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

CTSK

Mechanism

CTSK inhibitors(Cathepsin K inhibitors)

Therapeutic Areas

Eye Diseases

Active Indication

Glaucoma, Open-Angle

Inactive Indication

Osteoarthritis, KneeOsteoporosisOsteoporosis, Postmenopausal

Originator Organization

Novartis Pharma AG

Active Organization

The Indiana University School of Medicine

Inactive Organization

Novartis Pharmaceuticals Corp.

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure

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 Date17 May 2005

Sponsor / Collaborator-

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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17

Literatures (Medical) associated with Balicatib

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.

04 May 2022·Expert Opinion on Therapeutic PatentsQ2 · MEDICINE

A patent review on cathepsin K inhibitors to treat osteoporosis (2011 – 2021)

Q2 · MEDICINE

Review

Author: Lameiro, Rafael F. ; Montanari, Carlos A. ; Leitão, Andrei ; Rocho, Fernanda R. ; Lameira, Jerônimo ; Bonatto, Vinícius

INTRODUCTIONCathepsin K (CatK) is a lysosomal cysteine protease and the predominant cathepsin expressed in osteoclasts, where it degrades the bone matrix. Hence, CatK is an attractive therapeutic target related to diseases characterized by bone resorption, like osteoporosis.AREAS COVEREDThis review summarizes the patent literature from 2011 to 2021 on CatK inhibitors and their potential use as new treatments for osteoporosis. The inhibitors were classified by their warheads, with the most explored nitrile-based inhibitors. Promising in vivo results have also been disclosed.EXPERT OPINIONAs one of the most potent lysosomal proteins whose primary function is to mediate bone resorption, cathepsin K remains an excellent target for therapeutic intervention. Nevertheless, there is no record of any approved drug that targets CatK. The most notable cases of drug candidates targeting CatK were balicatib and odanacatib, which reached Phase II and III clinical trials, respectively, but did not enter the market. Further developments include exploring new chemical entities beyond the nitrile-based chemical space, with improved ADME and safety profiles. In addition, CatK's role in cancer immunoexpression and its involvement in the pathophysiology of osteo- and rheumatoid arthritis have raised the race to develop activity-based probes with excellent potency and selectivity.

01 Jan 2021·Molecular Biology ReportsQ4 · BIOLOGY

Inhibitory effect of cathepsin K inhibitor (ODN-MK-0822) on invasion, migration and adhesion of human breast cancer cells in vitro

Q4 · BIOLOGY

Article

Author: Samuel, Shila ; Kottaiswamy, Amuthavalli ; Kalaiselvan, Parkavi ; Padmanaban, Abirami ; Premsingh, Riya ; Soma, Mathangi ; Vashum, Yaongamphi

Approximately 90% of patients with advanced breast cancer develop bone metastases; an event that results in severe decrease of quality of life and a drastic deterioration in prognosis. Therefore, to increase the survival of breast cancer patients, the development of new therapeutic strategies to impair metastatic process and skeletal complications is critical. Previous studies on the role of cathepsin K (CTSK) in metastatic spreading led to several strategies for inhibition of this molecule such as MIV-711 (Medivir), balicatib and odanacatib (ODN) which were on trial in the past. The present study intended to assess the anti-metastatic efficacy of ODN in breast cancer cells. Human breast cancer cell lines MDA-MB-231 were treated with different concentrations of ODN and performed invasion, adhesion and migration assays and, RT-PCR and western blot to evaluate the effect of ODN on the metastatic potential of breast cancer cells. ODN markedly decreased wound healing cell migration, invasion and adhesion at a dose dependent manner. ODN inhibits cell invasion by decreasing the matrix metalloproteinase (MMP-9) with the upregulation of TIMP-1 expression. ODN effectively inhibited the phosphorylation of extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal Kinase (JNK), and blocked the expression of β-integrins and FAK proteins. ODN also significantly inhibited PI3K downstream targets Rac1, Cdc42, paxillin and Src which are critical for cell adhesion, migration and cytoskeletal reorganization. ODN exerts anti-metastatic action through inhibition of signaling pathway for MMP-9, PI3K and MAPK. This indicates potential therapeutic effects of ODN in the treatment of metastatic breast cancer.

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	US	Novartis Pharmaceuticals Corp.	01 Dec 2004
Osteoarthritis, Knee	Phase 3	DE	Novartis Pharmaceuticals Corp.	01 Dec 2004
Osteoporosis	Phase 3	-	Novartis Pharmaceuticals Corp.	01 Feb 2004
Glaucoma, Open-Angle	Preclinical	US	The Indiana University School of Medicine	01 Jun 2021
Osteoporosis, Postmenopausal	Discovery	CA	-	-
Osteoporosis, Postmenopausal	Discovery	US	-	-
Osteoporosis, Postmenopausal	Discovery	JP	-	-
Osteoporosis, Postmenopausal	Discovery	-	-	-