Repositioning Candidate Details

Candidate ID: R1394
Source ID: DB11712
Source Type: approved; investigational
Compound Type: small molecule
Compound Name: Tezacaftor
Synonyms: Tezacaftor
Molecular Formula: C26H27F3N2O6
SMILES: CC(C)(CO)C1=CC2=CC(NC(=O)C3(CC3)C3=CC=C4OC(F)(F)OC4=C3)=C(F)C=C2N1C[C@@H](O)CO
Structure:
DrugBank Description: Tezacaftor is a drug of the cystic fibrosis transmembrane conductance regulator (CFTR) potentiator class. It was developed by Vertex Pharmaceuticals and FDA approved in combination with to manage cystic fibrosis. This drug was approved by the FDA on February 12, 2018. Cystic Fibrosis is an autosomal recessive disorder caused by one of several different mutations in the gene for the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, an ion channel involved in the transport of chloride and sodium ions across cell membranes. CFTR is active in epithelial cells of organs such as of the lungs, pancreas, liver, digestive system, and reproductive tract. Alterations in the CFTR gene result in altered production, misfolding, or function of the protein and consequently abnormal fluid and ion transport across cell membranes. As a result, CF patients produce thick, sticky mucus that clogs the ducts of organs where it is produced making patients more susceptible to complications such as infections, lung damage, pancreatic insufficiency, and malnutrition.
CAS Number: 1152311-62-0
Molecular Weight: 520.505
DrugBank Indication: Tezacaftor is combined with ivacaftor in one product for the treatment of cystic fibrosis (CF) in patients aged 12 years or older with two copies of the _F508del_ gene mutation or at least one mutation in the CFTR gene that is responsive to this drug. Tezacaftor, when used in combination with ivacaftor and in the product Trikafta, is also indicated for the treatment of CF in patients 12 years of age and older that have at least one _F508del_ mutation in the CFTR gene.
DrugBank Pharmacology: Clinical studies have shown a significant decrease in sweat chloride and an increase in the forced expiratory volume (FEV), a measure of lung function, following Tevacaftor/Ivacaftor therapy. Phase 3 clinical studies have shown that a significant increase in forced expiratory volume was attained at 4 and 8 weeks after initiating this drug. The above effects lead to improvement of the respiratory symptoms of cystic fibrosis. Tezacaftor does not induce clinically significant QT prolongation. When given with ivacaftor, tezacaftor can lead to liver transaminase elevations. Testing of transaminases (ALT and AST) levels should occur before starting this combination every 3 months during the first year of treatment, and every year afterwards. Patients with a history of transaminase elevations should be monitored more frequently.
DrugBank MoA: The transport of charged ions across cell membranes is normally achieved through the actions of the cystic fibrosis transmembrane regulator (CFTR) protein. This protein acts as a channel and allows for the passage of chloride and sodium. This process affects the movement of water in and out of the tissues and impacts the production of mucus that lubricates and protects certain organs and body tissues, including the lungs. In the _F508del_ mutation of the CFTR gene, one amino acid is deleted at the position 508, therefore, the CFTR channel function is compromised, resulting in thickened mucus secretions. CFTR correctors such as tezacaftor aim to repair F508del cellular misprocessing. This is done by modulating the position of the CFTR protein on the cell surface to the correct position, allowing for adequate ion channel formation and increased in water and salt movement through the cell membrane. The concomitant use of ivacaftor is intended to maintain an open channel, increasing the transport of chloride, reducing thick mucus production.
Targets: Cystic fibrosis transmembrane conductance regulator activator
Inclusion Criteria: Therapeutic strategy associated

Strategy ID Strategy Synonyms Related Targets Related Drugs
S03 Anti-fibrosis fibrosis Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name

Diseases ID DO ID Disease Name Definition Class