PRLX-93936 dihydrochloride 

PRLX-93936 dihydrochloride is a molecular Glues that binds to and reprograms the TRIM21 ubiquitin ligase to degrade nuclear pore complexes. PRLX-93936 dihydrochloride 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 dihydrochloride induces the loss of short-lived cytoplasmic mRNA transcripts, triggers cancer cell apoptosis (Apoptosis), and inhibits the activated Ras pathway. PRLX-93936 dihydrochloride inhibits HIF-1 under hypoxic conditions (IC₅₀ = 0.09 μM in cell-based reporter gene assay). PRLX-93936 dihydrochloride suppresses tumor growth in mouse models and improves survival rates in mouse models of multiple myeloma. PRLX-93936 dihydrochloride is applicable to research related to pancreatic cancer and multiple myeloma^[1][2][3].

PRLX-93936 (72 h) dihydrochloride 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 nM; 30 min-10 h) dihydrochloride induces TRIM21-dependent degradation of nuclear pore complex proteins and MCL1 in PANC-1 human pancreatic cancer cells^[1].
PRLX-93936 (500 nM; 30 min) dihydrochloride 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 μM MG132 for 30 min, followed by treatment with 500 nM PRLX-93936 for 30 min or 2 h, and co-treated with 100 nM biotin for 30 min) dihydrochloride induces the translocation of TRIM21 to the nuclear pore complex in human pancreatic cancer cell line PANC-1. Treatment with 500 nM PRLX-93936 dihydrochloride for 30 min or 2 h results in close proximity between TRIM21 and nucleoporins such as NUP98^[1].
PRLX-93936 (2 h) dihydrochloride 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) dihydrochloride potently reduces the viability of cholangiopancreatic organoids with high TRIM21 expression, and induces TRIM21-dependent degradation of nuclear pore complex proteins.
PRLX-93936 (1-10 μM) dihydrochloride reduces HIF-1α protein accumulation under hypoxic conditions^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

PRLX-93936 (50-100 mg/kg, i.p.; 1-2 times daily; 21 days) dihydrochloride induces tumor volume reduction in PANC-1 and HS766T pancreatic cancer xenograft mice models, and triggers degradation of nuclear pore complex components in PANC-1 pancreatic cancer xenografts^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

437.36

C₂₁H₂₆Cl₂N₄O₂

1094210-96-4

Solid

White to off-white

O=C1N(C(CN2CCNCC2)=NC3=C1C=CC=C3)C4=CC=CC=C4OCC.Cl.Cl

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Yuan L, et al. Defining the Antitumor Mechanism of Action of a Clinical-stage Compound as a Selective Degrader of the Nuclear Pore Complex. Cancer Discov. 2025;15(12):2505-2529.  [Content Brief]

  [2]. Peter M Voorhees, MD, et al. An Open-Label, Dose Escalation, Multi-Center Phase 1 Study of PRLX 93936, an Agent Synthetically Active Against the Activated Ras Pathway, in the Treatment of Relapsed or Relapsed and Refractory Multiple Myeloma. Volume 124, Issue 21, 6 December 2014, Page 2140.

  [3]. Huang W, et al. Synthesis and evaluation of quinazolin-4-ones as hypoxia-inducible factor-1α inhibitors. Bioorg Med Chem Lett. 2011 Sep 15;21(18):5239-43.  [Content Brief]