Publications by authors named "R Rej"
In the SWI/SNF chromatin-remodeling complex, the mutually exclusive catalytic ATPase subunits SMARCA2 and SMARCA4 proteins have a synthetic-lethal relationship. Selectively targeting SMARCA2 for degradation is a promising and new therapeutic strategy for human cancers harboring inactivated mutated SMARCA4. In this study, we report the design, synthesis, and biological evaluation of novel SMARCA2/4 ligands and our subsequent design of PROTAC degraders using high-affinity SMARCA ligands and VHL-1 ligands.
View Article and Find Full Text PDFArticle Synopsis
- - Commutable secondary certified reference materials (CRMs) are crucial for ensuring consistent results in medical lab tests, highlighting the need for their sustainable availability.
- - The IFCC Working Group has released recommendations for assessing the commutability of these CRMs, although detailed studies can strain resources for producers.
- - A new equivalence assessment method allows for comparing replacement CRMs with established ones, potentially reducing resource needs while ensuring reliability through the inclusion of representative clinical samples.
Inhibition of estrogen receptor alpha (ERα) signaling is an established therapeutic approach for the treatment of ER-positive (ER+) breast cancers, but new therapeutic strategies are urgently needed to overcome clinical resistance. In the present study, we describe the discovery and extensive evaluation of ERD-12310A as an exceptionally potent and orally efficacious PROTAC degrader of ERα. ERD-12310A achieved a DC value of 47 pM and is 10 times more potent than ARV-471.
View Article and Find Full Text PDFArticle Synopsis
- Current therapies for ERα-positive breast cancer often face challenges due to clinical resistance, creating a need for new treatment options.
- Researchers have discovered ERD-1233, an oral drug that effectively degrades the ERα protein through innovative PROTAC technology.
- In preclinical models, ERD-1233 shows significant tumor regression and growth inhibition, suggesting it could be a valuable new therapy for treating ER+ breast cancer.
Article Synopsis
- Researchers have identified a new compound, CW-3308, that effectively degrades the protein BRD9, which is a key target for cancer therapy.
- CW-3308 shows very high potency, with a degradation capability below 10nM and over 90% efficiency in inhibiting BRD9 in specific cancer cell lines.
- The compound is also orally bioavailable, achieving a 91% bioavailability in mice and significantly reducing tumor growth in xenograft models, making it a strong candidate for treating various tumors linked to BRD9.