Delving into the Latest Updates on Olacaftor with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Olacaftor (USAN)

Target

CFTR x Ion channels

Action

stimulants, agonists

Mechanism

CFTR stimulants(Cystic fibrosis transmembrane conductance regulator stimulants), Ion channels agonists

Therapeutic Areas

Congenital DisordersDigestive System DisordersRespiratory Diseases+ [1]

Active Indication-

Inactive Indication

Cystic Fibrosis

Originator Organization

Vertex Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

Vertex Pharmaceuticals, Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC29H34FN3O4S

InChIKeyNHOUNZMCSIHKHJ-FQEVSTJZSA-N

CAS Registry1897384-89-2

This is a Phase 2, randomized, double-blind, placebo- and active-controlled, parallel group, multicenter study to evaluate the safety, tolerability, and efficacy of VX-440 in dual and triple combination with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F508del/F508del), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF).

Start Date01 Oct 2016

Sponsor / Collaborator

Vertex Pharmaceuticals, Inc.

NCT03486236

/ CompletedPhase 1

A Phase 1, Randomized, Double Blind, Placebo Controlled, Multiple Dose Escalation Study Evaluating Safety and Pharmacokinetics of VX-440 in Combination With VX-661/Ivacaftor in Healthy Adult Subjects

This study evaluated the safety and pharmacokinetics of multiple ascending doses of VX-440 in combination with tezacaftor/ivacaftor (TEZ/IVA) (triple combination [TC]) administered for 13 days to healthy male and female subjects

Start Date20 Jul 2016

Sponsor / Collaborator

Vertex Pharmaceuticals, Inc.

100 Clinical Results associated with Olacaftor

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100 Translational Medicine associated with Olacaftor

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100 Patents (Medical) associated with Olacaftor

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4

Literatures (Medical) associated with Olacaftor

01 Aug 2024·Infection, Genetics and Evolution

Identification of therapeutic drug target of Shigella Flexneri serotype X through subtractive genomic approach and in-silico screening based on drug repurposing

Article

Author: Tauseef, Saba ; Khan, Kanwal ; Abdellattif, Magda H ; Ahmed, Muhammad Hassan ; Jalal, Khurshid ; Al-Harrasi, Ahmed ; Khan, Ajmal ; Haroon, Urooj ; Uddin, Reaz

Shigellosis, induced by Shigella flexneri, constitutes a significant health burden in developing nations, particularly impacting socioeconomically disadvantaged communities. Designated as the second most prevalent cause of diarrheal illness by the World Health Organization (WHO), it precipitates an estimated 212,000 fatalities annually. Within the spectrum of S. flexneri strains, serotype X is notably pervasive and resilient, yet its comprehensive characterization remains deficient. The present investigation endeavors to discern potential pharmacological targets and repurpose existing drug compounds against S. flexneri serotype X. Employing the framework of subtractive genomics, the study interrogates the reference genome of S. flexneri Serotype X (strain 2,002,017; UP000001884) to delineate its proteome into categories of non-homologous, non-paralogous, essential, virulent, and resistant constituents, thereby facilitating the identification of therapeutic targets. Subsequently, a screening of approximately 9000 compounds from the FDA library against the identified drug target aims to delineate efficacious agents for combating S. flexneri serotype X infections. The application of subtractive genomics methodology yields prognostic insights, unveiling non-paralogous proteins (n = 4122), non-homologues (n = 1803), essential (n = 1246), drug-like (n = 389), resistant (n = 167), alongside 42 virulent proteins within the reference proteome. This iterative process culminates in the identification of Serine O-acetyltransferase as a viable drug target. Subsequent virtual screening endeavors to unearth FDA-approved medicinal compounds capable of inhibiting Serine O-acetyltransferase. Noteworthy candidates such as DB12983, DB15085, DB16098, DB16185, and DB16262 emerge, exhibiting potential for mitigating S. flexneri Serotype X. Despite the auspicious findings, diligent scrutiny is imperative to ascertain the efficacy and safety profile of the proposed drug candidates vis-à-vis S. flexneri.

01 Mar 2021·European Journal of Medicinal ChemistryQ1 · MEDICINE

Modulators of CFTR. Updates on clinical development and future directions

Q1 · MEDICINE

Review

Author: Golec, Anita ; Gravier-Pelletier, Christine ; Pastor, Alexandra ; Bardin, Emmanuelle ; Chevalier, Benoit ; Berhal, Farouk ; Semeraro, Michaela ; Hayes, Kate ; Prestat, Guillaume ; Hinzpeter, Alexandre ; Sermet-Gaudelus, Isabelle ; Pranke, Iwona

Cystic fibrosis (CF) is the most frequent life-limiting autosomal recessive disorder in the Caucasian population. It is due to mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Current symptomatic CF therapies, which treat the downstream consequences of CFTR mutations, have increased survival. Better knowledge of the CFTR protein has enabled pharmacologic therapy aiming to restore mutated CFTR expression and function. These CFTR "modulators" have revolutionised the CF therapeutic landscape, with the potential to transform prognosis for a considerable number of patients. This review provides a brief summary of their mechanism of action and presents a thorough review of the results obtained from clinical trials of CFTR modulators.

Research Journal of Biotechnology

In silico analysis and docking studies on cystic fibrosis to identify potential drug candidates

Author: Abhishek, Sengupta ; Seema, Bhatnagar ; Priyanka, Narad ; Nishita, Verma

A review.Cystic fibrosis (CF) is a multi-system autosomal recessive disorder due to defects in the CF transmembrane conductance regulator (CFTR) protein, most commonly affecting the lungs.Despite being thought of as an uncommon ailment, cystic fibrosis (CF) is the most common monogenic sickness among those who are mostly of European descent.It is estimated that 1% of people worldwide have a single faulty copy of the CFTR gene.A recent pilot study using NGS technol. in 2020 from Delhi's Sir Ganga Ram Hospital, indicated the prevalence of cystic fibrosis mutations of 1 in 2,000 persons.This is much higher than the earlier estimated prevalence as the disease was rare in the Indian population.The most common mutations are delta F 508 and G551D which are also prevalent in the Indian population.The use of computer-aided drug design (CADD) can reduce the time needed for the discovery, evaluation and structure-optimization of new therapeutic candidates.CADD may be advantageous for pharmaceuticals with logical designs.Multiple breakthroughs have been made in the study of small mol. medicines and natural chems. for the treatment of cystic fibrosis.Seven well-known small-mol. medications that target the CFTR were chosen including Ivacaftor, Lumacaftor, Tezacaftor, Galicaftor, Olacaftor, Navocaftor and Elexacaftor.The natural compounds chosen were Genistein, Curcumin and Resveratrol.They were all docked onto the CFTR target protein and the effectiveness of the therapy was evaluated based on the docking scores.It was also planned to investigate if the combined impacts of these two different kinds of mols. may help in the development of new medications.To achieve this, combinatorial docking was tried using the small mol. market medication and the natural chem. that showed the best interaction with the target protein.Finally, based on mol. docking studies, Lonidamine, a well-known medicinal mol. was used to determine whether it may target cystic fibrosis.

100 Deals associated with Olacaftor

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External Link

KEGG	Wiki	ATC	Drug Bank
D11402	-	-	DB16262

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cystic Fibrosis	Phase 2	United Kingdom	Vertex Pharmaceuticals, Inc.	01 Oct 2016
Cystic Fibrosis	Phase 2	Germany	Vertex Pharmaceuticals, Inc.	01 Oct 2016
Cystic Fibrosis	Phase 2	Spain	Vertex Pharmaceuticals, Inc.	01 Oct 2016
Cystic Fibrosis	Phase 2	United States	Vertex Pharmaceuticals, Inc.	01 Oct 2016
Cystic Fibrosis	Phase 2	Belgium	Vertex Pharmaceuticals, Inc.	01 Oct 2016
Cystic Fibrosis	Phase 2	Denmark	Vertex Pharmaceuticals, Inc.	01 Oct 2016
Cystic Fibrosis	Phase 2	Austria	Vertex Pharmaceuticals, Inc.	01 Oct 2016
Cystic Fibrosis	Phase 2	Australia	Vertex Pharmaceuticals, Inc.	01 Oct 2016
Cystic Fibrosis	Phase 2	Canada	Vertex Pharmaceuticals, Inc.	01 Oct 2016
Cystic Fibrosis	Phase 2	Italy	Vertex Pharmaceuticals, Inc.	01 Oct 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02951182 (CTgov)	Phase 2	Cystic Fibrosis	74	Matched Placebo (Part 1: Placebo - Cohort 1A and 1B Combined)	cotryjsjdn(yunqjyszul) = oziydffcji ovcehjiyhf (zsnzgqspuy, kuzpkamtev - xnbblghiym) View more	-	28 Aug 2020
				IVA+TEZ+VX-440 (Part 1 Cohort 1A: Triple Combination (TC))	cotryjsjdn(yunqjyszul) = ovuyjbzrmi ovcehjiyhf (zsnzgqspuy, zfuffodapj - zlhupekfmo) View more