CX-546 – (215923-54-9)

CX-546 is a first-generation and selective benzamide-type positive AMPAR modulator, also known as an ampakine agent, developed by Cortex Pharmaceuticals. It has been investigated for its potential in treating schizophrenia and has shown significant efficacy in reversing respiratory depression induced by sedative drugs such as opioids and barbiturates. CX-546 enhances cognitive function and has been found to increase brain-derived neurotrophic factor (BDNF) levels in the brain. Despite its promising effects, CX-546 suffers from limited oral bioavailability.

In the realm of cancer research, CX-5461, a compound structurally related to CX-546, has emerged as a potent DNA G-quadruplex stabilizer. It exhibits selective lethality in BRCA1/2 deficient tumors, making it a promising candidate for targeted cancer therapy. CX-5461 works by inducing replication-dependent DNA damage and stabilizing G-quadruplex structures, which are particularly detrimental to cells with deficiencies in DNA damage repair pathways, such as those with BRCA1/2 mutations. This selective toxicity has been demonstrated in various cell lines and in vivo models, including patient-derived xenografts (PDX) resistant to standard treatments like PARP inhibitors and platinum-based drugs.

CX-5461 is currently in advanced phase I clinical trials for patients with BRCA1/2 deficient tumors, highlighting its translational potential. The drug’s ability to induce DNA damage and its reliance on the BRCA and NHEJ pathways for repair suggest its applicability in treating a broader range of cancers with deficiencies in DNA damage repair. Furthermore, CX-5461’s effectiveness in chemo-resistant tumors underscores its potential as a novel therapeutic option for patients who have exhausted other treatment avenues.

The above information is displayed for information purpose only, and has not been reviewed by EON nor does EON attests or validates the accuracy nor does it constitutes a recommendation or validation.

Sources:

https://en.wikipedia.org/wiki/CX-546
https://pubchem.ncbi.nlm.nih.gov/compound/2890
https://www.medchemexpress.com/CX546.html
https://www.medkoo.com/products/9806
https://pubmed.ncbi.nlm.nih.gov/15659236/
https://www.nature.com/articles/ncomms14432