Repositioning Candidate Details
| Candidate ID: | R1561 |
| Source ID: | DB15444 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Elexacaftor |
| Synonyms: | Elexacaftor |
| Molecular Formula: | C26H34F3N7O4S |
| SMILES: | C[C@@H]1CN(C2=NC(=CC=C2C(=O)NS(=O)(=O)C2=CN(C)N=C2C)N2C=CC(OCC(C)(C)C(F)(F)F)=N2)C(C)(C)C1 |
| Structure: |
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| DrugBank Description: | Elexacaftor (previously VX-445) is a small molecule, next-generation corrector of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. It received FDA approval in October 2019 in combination with and as the combination product Trikafta<sup>TM</sup>. Elexacaftor is considered a next-generation CFTR corrector as it possesses both a different structure and mechanism as compared to first generation correctors like tezacaftor. While dual corrector/potentiator combination therapy has proven useful in the treatment of a subset of CF patients, their use is typically limited to patients who are homozygous for the _F508del-CFTR_ gene. Elexacaftor, along with , was designed to fill the need for an efficacious CF therapy for patients who are heterozygous for _F508del-CFTR_ and a gene that does not produce protein or produces proteins unresponsive to ivacaftor or tezacaftor. The triple combination product Trikafta<sup>TM</sup>, manufactured by Vertex Pharmaceuticals, is the first product approved for the treatment of CF in individuals who are either homo- _or_ heterozygous for the _F508del-CFTR_ gene - this represents approximately 70-90% of all CF patients. |
| CAS Number: | 2216712-66-0 |
| Molecular Weight: | 597.66 |
| DrugBank Indication: | Elexacaftor, in combination with and as the combination product Trikafta<sup>TM</sup>, is indicated for the treatment of cystic fibrosis (CF) in patients 12 years of age and older who have at least one _F508del_ mutation in the CTFR gene. |
| DrugBank Pharmacology: | As a CFTR corrector, elexacaftor works to increase the amount of mature CFTR proteins present on the surface of cells. When used in combination with CFTR potentiators, which enhance the function of cell-surface CFTR proteins, drugs like elexacaftor help to improve a variety of multi-organ cystic fibrosis symptoms, including lung function, nutritional status, and overall quality of life. Trikafta<sup>TM</sup>, the triple combination product containing elexacaftor, may cause elevations in liver transaminases. Liver function testing should be conducted prior to beginning Trikafta, every 3 months for the first year of treatment, and annually thereafter. |
| DrugBank MoA: | Cystic fibrosis (CF) is the result of a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR proteins produced by this gene are transmembrane ion channels that move sodium and chloride across cell membranes - water follows the flow of chloride ions to the cell surface, which consequently helps to hydrate the surface of the cell and thin the secretions (i.e. mucous) around the cell. Mutations in the CFTR gene produce CFTR proteins of insufficient quantity and/or function, leading to defective ion transport and a build-up of thick mucous throughout the body that causes multi-organ disease involving the pulmonary, gastrointestinal, and pancreatic systems (amongst others). The most common CFTR mutation, the _F508del_ mutation, is estimated to account for 70 to 90% of all CFTR mutations and results in severe processing and trafficking defects of the CFTR protein. Elexacaftor is a CFTR corrector that modulates CFTR proteins to facilitate trafficking to the cell surface for incorporation into the cell membrane. The end result is an increase in the number of mature CFTR proteins present at the cell surface and, therefore, improved ion transport and CF symptomatology. Elexacaftor is used in combination with tezacaftor, another CFTR corrector with a different mechanism of action, and ivacaftor, a CFTR potentiator that improves the function of CFTR proteins on the cell surface - this multi-faceted, triple-drug approach confers a synergistic effect beyond that seen in typical corrector/potentiator dual therapy regimens. |
| Targets: | Cystic fibrosis transmembrane conductance regulator modulator |
| 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 |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|