PRLX 93936
/ Prolexys
- LARVOL DELTA
Home
Next
Prev
1 to 5
Of
5
Go to page
1
October 01, 2025
Therapeutic targeting of the nuclear pore complex with molecular glue degraders in pancreatic cancer Free
(AACRPanCa 2025)
- "PRLX-93936, a derivative of erastin, was previously tested in early-phase oncology clinical trials despite having an unknown mechanism. Planned next steps include evaluating drug combinations and further pre-clinical toxicology for de-risking. The discovery of potent TRIM21-mediated NPC degraders presents unexpected new opportunities for PDAC therapy."
Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Targeted Protein Degradation • KRAS • TRIM21
September 04, 2025
Defining the antitumor mechanism of action of a clinical-stage compound as a selective degrader of the nuclear pore complex.
(PubMed, Cancer Discov)
- "Through large-scale phenotypic profiling of cancer cell lines, genome-scale functional genomic modifier screens, and mass spectrometry-based proteomics, we discovered that the clinical drug PRLX-93936 is a molecular glue that binds and reprograms the TRIM21 ubiquitin ligase to degrade the nuclear pore complex...Direct compound binding to TRIM21 was confirmed via surface plasmon resonance and x-ray crystallography, while compound-induced TRIM21-nucleoporin complex formation was demonstrated through multiple orthogonal approaches in cells and in vitro. Phenotype-guided optimization yielded compounds with 10-fold greater potency and drug-like properties with robust pharmacokinetics and efficacy against pancreatic cancer xenografts and patient-derived organoids."
Journal • Oncology • Pancreatic Cancer • Solid Tumor • Targeted Protein Degradation • TRIM21
July 17, 2025
Elaboration of molecular glues that target TRIM21 into TRIMTACs that degrade protein aggregates.
(PubMed, Nat Commun)
- "Additionally, we elaborate PRLX-93936 to a heterobifunctional degrader that uses wild-type TRIM21 to degrade a multimeric protein. Together, our work creates opportunities for targeted protein degradation and enables the design of additional TRIM21-targeting glues and Proteolysis-Targeting Chimeras (PROTACs)."
Journal • Oncology • Targeted Protein Degradation • TRIM21
April 10, 2025
TRIM21-NUP98 Interface Accommodates Structurally Diverse Molecular Glue Degraders.
(PubMed, ACS Chem Biol)
- "Here, we analyzed public compound toxicity data across a large collection of cell lines and identified two additional molecular glue degraders, PRLX 93936 and BMS-214662, which engage the TRIM21-NUP98 interface to induce selective degradation of nuclear pore proteins. Additionally, we confirmed that HGC652, another TRIM21-dependent molecular glue degrader, also binds at this interface. Together with our previously characterized degrader (S)-ACE-OH, these findings demonstrate that the TRIM21-NUP98 interface can accommodate structurally diverse molecular glue degraders."
Journal • Targeted Protein Degradation • NUP98 • TRIM21
July 09, 2021
Cisplatin synergizes with PRLX93936 to induce ferroptosis in non-small cell lung cancer cells.
(PubMed, Biochem Biophys Res Commun)
- "In the current study, we showed that cisplatin and PRLX93936, an analog of erastin that has been tested in clinical trials, demonstrated synergistic effects against non-small cell lung cancer (NSCLC) cells. Nrf2 silencing increased this sensitivity while inhibition of Keap1 attenuated it. Overall, our data reveal a new effective treatment for NSCLC by synergizing cisplatin and PRLX93936 to induce ferroptosis."
Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • GPX4
1 to 5
Of
5
Go to page
1