Comorbid Conditions in Relation to Controlled Substance Abuse.

Dental patients who experience comorbid psychiatric and medical conditions present an elevated risk of medication misuse, abuse, substance use disorders, and overdose. The authors review the role of notable comorbidities in predicting the development of substance use disorder, including medical, psychiatric, and other psychosocial factors that can be assessed in general dental practice. Psychiatric disorders commonly cooccur with substance abuse, and these typically include anxiety disorders, mood disorders (major depression, bipolar), posttraumatic stress, as well as sleep and eating disorders.

Selective estrogen receptor degraders with novel structural motifs induce regression in a tamoxifen-resistant breast cancer xenograft.

Potent estrogen receptor ligands typically contain a phenolic hydrogen-bond donor. The indazole of the selective estrogen receptor degrader (SERD) ARN-810 is believed to mimic this. Disclosed herein is the discovery of ARN-810 analogs which lack this hydrogen-bond donor.

Optimization of an indazole series of selective estrogen receptor degraders: Tumor regression in a tamoxifen-resistant breast cancer xenograft.

Selective estrogen receptor degraders (SERDs) have shown promise for the treatment of ER+ breast cancer. Disclosed herein is the continued optimization of our indazole series of SERDs. Exploration of ER degradation and antagonism in vitro followed by in vivo antagonism and oral exposure culminated in the discovery of indazoles 47 and 56, which induce tumor regression in a tamoxifen-resistant breast cancer xenograft.