PRLX-93936

PRLX-93936 is a molecular Glues that binds to and reprograms the TRIM21 ubiquitin ligase to degrade nuclear pore complexes. PRLX-93936 binds to TRIM21, forms a ternary complex with TRIM21 and NUP98, and mediates the ubiquitination and proteasomal degradation of NUP98 and other nuclear pore complex proteins. PRLX-93936 induces the loss of short-lived cytoplasmic mRNA transcripts, triggers cancer cell apoptosis (Apoptosis), and inhibits the activated Ras pathway. PRLX-93936 suppresses tumor growth in mouse models and improves survival rates in mouse models of multiple myeloma. PRLX-93936 is applicable to research related to pancreatic cancer and multiple myeloma^[1][2]. In Vitro:PRLX-93936 (72 h) selectively inhibits the viability of human cancer cell lines, with the strongest activity observed in pancreatic and head and neck cancer cell lines, and reduces the survival rate of human cancer cell lines with high TRIM21 expression^[1].
PRLX-93936 (500 nmol; 30 min-10 h) induces TRIM21-dependent degradation of nuclear pore complex proteins and MCL1 in PANC-1 human pancreatic cancer cells^[1].
PRLX-93936 (500 nmol/L; 30 min) induces TRIM21-dependent ubiquitination of nuclear pore complex proteins in human pancreatic cancer cell line PANC-1 pretreated with MG132 (HY-13259)^[1].
PRLX-93936 (cells are pretreated with 1 μmol/L MG132 for 30 min, followed by treatment with 500 nmol/L PRLX-93936 for 30 min or 2 h, and co-treated with 100 nmol/L biotin for 30 min) induces the translocation of TRIM21 to the nuclear pore complex in human pancreatic cancer cell line PANC-1. Treatment with 500 nmol/L PRLX-93936 for 30 min or 2 h results in close proximity between TRIM21 and nucleoporins such as NUP98^[1].
PRLX-93936 (2 h) acts as a molecular glue that induces a direct, dose-dependent interaction between TRIM21 and NUP98 in HEK293T cells^[1].
PRLX-93936 (for 5 days) potently reduces the viability of patient-derived cholangiopancreatic organoids with high TRIM21 expression, and induces TRIM21-dependent degradation of nuclear pore complex proteins. In Vivo:PRLX-93936 (i.p.; 1-2 times daily; 21 days, 50-100 mg/kg) induces tumor volume reduction in PANC-1 and HS766T pancreatic cancer xenograft models, and triggers degradation of nuclear pore complex components in PANC-1 pancreatic cancer xenografts^[1].