PRLX-93936
Based on 1 Customer Validation
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 inhibits HIF-1 under hypoxic conditions (IC50 = 0.09 μM in cell-based reporter gene assay). 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.
For research use only. We do not sell to patients.
- Purity : 98.31%
- CAS No.: 903499-49-0
- Formula: C21H24N4O2
- Molecular Weight:364.44
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Storage:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
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HY-D0819A
CY5-SE triethylamine saltFluorescent Probe -
HY-15893
DMOGHIF-PH Inhibitor -
HY-13426
RoxadustatHIF-PH Inhibitor -
HY-10231
PX-478HIF-1α Inhibitor -
HY-13671
LW6Apoptosis Inducer -
HY-15836
BAY 87-2243HIF-1 Inhibitor -
HY-15893R
DMOG (Standard)HIF-PH Inhibitor -
HY-16187
EL-102Hif1α Inhibitor -
HY-13426R
Roxadustat (Standard)HIF-PH Inhibitor -
HY-15893G
DMOG (GMP)HIF-1α Stabilizer -
HY-10231R
PX-478 (Standard)Reference Standard
Biological Activity
Description
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| ME-180 | IC50 |
0.09 μM
Compound: 16
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Inhibition of hypoxia-induced HIF1alpha activation in human ME180 cells by HRE3-Bla-luciferase reporter gene assay
Inhibition of hypoxia-induced HIF1alpha activation in human ME180 cells by HRE3-Bla-luciferase reporter gene assay
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[PMID: 21831635] |
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 nM; 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 nM; 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 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) induces the translocation of TRIM21 to the nuclear pore complex in human pancreatic cancer cell line PANC-1. Treatment with 500 nM 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 cholangiopancreatic organoids with high TRIM21 expression, and induces TRIM21-dependent degradation of nuclear pore complex proteins.
PRLX-93936 (1-10 μM) 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. Further protocols information, click here.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (female, 6 weeks old, subcutaneous xenograft with 5×106 PANC-1 cells/HS766T cells/PANC-1 cells)[1]
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Dosage:50, 100 mg/kg
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Administration:i.p.; daily; 21 days/i.p.; two daily doses
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Result:Reduced average tumor volume.
Depleted several nucleoporins (NUP98, NUP96, NUP35) in tumor tissue, confirming on-target degradation of nuclear pore complex components in vivo.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 903499-49-0
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Appearance Solid
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Molecular Weight 364.44
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Formula C21H24N4O2
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Color White to off-white
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SMILES
O=C1N(C(CN2CCNCC2)=NC3=C1C=CC=C3)C4=CC=CC=C4OCC
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
In Vitro:
DMSO : ≥ 100 mg/mL (274.39 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
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.
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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (6.86 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (6.86 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocols
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Dual Luciferin reporter gene assay
Luciferin reporter gene assay is a reporting system to detect the activity of Firefly Luciferase using luciferin as a substrate, which is often used in the research of miRNA target gene verification and promoter transcriptive activity regulation. Dual luciferase usually refers to Firefly luciferase and Renilla luciferase.
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Patient-Derived Xenograft (PDX)
Patient-derived xenograft (PDX) models are generated by engrafting primary human tumor tissue directly into immunodeficient mice, allowing in vivo propagation of patient tumor biology without initial in vitro adaptation. These models are used to preserve key histopathological and molecular characteristics of the original tumor and enable assessment of tumor growth dynamics and therapeutic response in a living organism. The biological readout is tumor engraftment and subsequent growth in the murine host, which reflects the ability of human tumor cells to survive, vascularize, and expand in an immunocompromised microenvironment.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Patient-Derived Orthotopic Xenograft (PDOX)
Patient-derived orthotopic xenograft (PDOX) modeling implants fresh patient tumor tissue or patient-derived tumor cells into the anatomically corresponding organ or tissue site of immunodeficient mice, usually by surgical orthotopic implantation, to preserve patient tumor histology, local microenvironmental context, invasion, metastatic behavior, and treatment-response features better than subcutaneous implantation. PDOX readouts include tumor engraftment, orthotopic tumor growth, local invasion, metastasis, recurrence after resection, histologic similarity to the donor tumor, biomarker retention, molecular concordance, survival, and response or resistance to therapy. PDOX models are used for preclinical drug testing and individualized therapy evaluation, but engraftment success varies by tumor type and specimen quality.
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Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
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Orthotopic Cell-Line Xenograft
Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi
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Directly Induced Neuron Culture
Directly induced neuron culture converts somatic cells, most commonly fibroblasts, into induced neurons without passing through a pluripotent or neural progenitor stage; classic evidence shows that mouse fibroblasts can be converted by Ascl1, Brn2/Pou3f2, and Myt1l, human fibroblasts can be converted by defined neuronal transcription factors, and human fibroblasts can also be converted by miR-9/9-124 with neurogenic or subtype-specifying transcription factors. The readout is acquisition of neuronal identity and function, assessed by neuronal morphology, neuronal markers such as Tuj1/βIII-tubulin, MAP2, synapsin, and subtype markers when relevant, together with functional assays such as action-potential firing, synaptic activity, and electrophysiology.
Purity & Documentation
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Data Sheet (278 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[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]
[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]
Complete Stock Solution Preparation Table
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.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.7439 mL | 13.7197 mL | 27.4394 mL | 68.5984 mL |
| 5 mM | 0.5488 mL | 2.7439 mL | 5.4879 mL | 13.7197 mL | |
| 10 mM | 0.2744 mL | 1.3720 mL | 2.7439 mL | 6.8598 mL | |
| 15 mM | 0.1829 mL | 0.9146 mL | 1.8293 mL | 4.5732 mL | |
| 20 mM | 0.1372 mL | 0.6860 mL | 1.3720 mL | 3.4299 mL | |
| 25 mM | 0.1098 mL | 0.5488 mL | 1.0976 mL | 2.7439 mL | |
| 30 mM | 0.0915 mL | 0.4573 mL | 0.9146 mL | 2.2866 mL | |
| 40 mM | 0.0686 mL | 0.3430 mL | 0.6860 mL | 1.7150 mL | |
| 50 mM | 0.0549 mL | 0.2744 mL | 0.5488 mL | 1.3720 mL | |
| 60 mM | 0.0457 mL | 0.2287 mL | 0.4573 mL | 1.1433 mL | |
| 80 mM | 0.0343 mL | 0.1715 mL | 0.3430 mL | 0.8575 mL | |
| 100 mM | 0.0274 mL | 0.1372 mL | 0.2744 mL | 0.6860 mL |
PRLX-93936 Related Classifications
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