PRT3789
PRT3789 is a selective SMARCA2 PROTAC degrader (DC50 in HeLa cell: 0.72 nM for SMARCA2, 14 nM for SMARCA4). PRT3789 forms a stable ternary complex with Von Hippel-Lindau (VHL) E3 ligase, induces polyubiquitination at SMARCA2-specific lysine residues, and drives proteasome-dependent SMARCA2 degradation. PRT3789 disrupts SWI/SNF chromatin remodeling complex integrity, induces dissociation of specific subunits, suppresses oncogenic gene expression, reduces chromatin accessibility, and upregulates antigen processing/presentation-related gene expression. PRT3789 induces synthetic lethality, inhibits proliferation and colony formation, and drives tumor growth inhibition and regression in SMARCA4-deficient contexts. PRT3789 can be used for the research of SMARCA4-mutated solid tumors, non-small cell lung cancer, endometrial cancer, colorectal cancer, bladder cancer, esophageal cancer, ovarian cancer, and gastric cancer.
(Pink: SMARCA2 ligand (HY-44824); Blue: VHL ligand (HY-159465); Black: linker).
For research use only. We do not sell to patients.
- CAS No.: 2755761-78-3
- Formula: C47H58N10O6S
- Molecular Weight:891.09
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Storage:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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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
Biological Activity
Description
IC50 & Target
[1]|
SMARCA2 0.72 nM (DC50) |
SMARCA4 14 nM (DC50) |
In Vitro
PRT3789 selectively induces polyubiquitination of wild-type SMARCA2 BD over SMARCA4 BD, with critical contributions from SMARCA2-specific lysine residues K1405 and K1445 and the unique extended loop region of SMARCA2 BD[1].
PRT3789 (0.1-1000 nM; 5-7 days cell viability, 18-21 days clonogenic assays) selectively inhibits proliferation and colony formation of SMARCA4-deficient cancer cells, inducing G1 cell-cycle arrest and p21 upregulation, while sparing SMARCA4 wild-type cells[1].
PRT3789 potently and selectively degrades SMARCA2 in HeLa cells, with a DC50 of 0.72 nM (94% Dmax%) and 19-fold selectivity relative to SMARCA4[2].
PRT3789 (0.1-1000 nM) selectively inhibits the proliferation of SMARCA4-deleted/KO cancer cell lines (NCI-H1693, NCI-H838, HT1080 SM4 KO), with no effect on SMARCA4 WT cell lines, as measured by clonogenic assay[2].
PRT3789 (50 nM) completely degrades SMARCA2 in SMARCA4-deleted NCI-H1693 cells, and induces dissociation of specific SWI/SNF complex subunits while leaving the core DNA finger complex intact[2].
PRT3789 (50 nM; 72 h) alters gene expression in SMARCA4-deleted NCI-H1693 cells, downregulating oncogenic and cell cycle-related genes and upregulating immunogenicity-related genes, with 600 total differentially expressed genes[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:SMARCA4-deficient (NCI-H1693, NCI-H838, HT1080 SMARCA4 KO, patient-derived tumor cultures), SMARCA4 wild-type (Calu-6, NCI-H520, HT1080 WT) cancer cell lines
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Concentration:0.1, 1, 10, 100, 1000 nM
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Incubation Time:5-7 days (cell viability); 18-21 days (clonogenic assays)
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Result:Significantly inhibited proliferation of SMARCA4-deficient or low-expressing cancer cells and patient-derived tumor cultures, with minimal effects on SMARCA4 wild-type or SMARCA2/4 dual-loss cells.
Dose-dependently inhibited colony formation in SMARCA4-deficient cell lines (NCI-H1693, NCI-H838, HT1080 SMARCA4 KO) but had no effect on SMARCA4 wild-type lines (Calu-6, NCI-H520, HT1080 WT).
Induced G1 cell-cycle arrest and increased p21 expression in SMARCA4-deficient NCI-H838 cells, but not in SMARCA4 wild-type Calu-6 cells.
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Cell Line:Isogenic SMARCA4 WT and SM4 KO HT1080 cells
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Concentration:10 nM, 1000 nM
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Incubation Time:up to 8 days
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Result:Inhibited proliferation of SMARCA4 KO HT1080 cells, but not SMARCA4 WT HT1080 cells.
Parmacokinetics
In Vivo
PRT3789 (100 mg/kg; s.c.; once weekly) induces potent tumor growth inhibition in the SMARCA4G12C-mutant CTG-0493 esophageal PDX model[1].
PRT3789 (100 mg/kg; s.c.; every 3 days (Q3D)) induces potent tumor growth inhibition and robust on-target SMARCA2 degradation (>90% reduction) in the NCI-H838 xenograft model[1].
PRT3789 (200 mg/kg; s.c.; every 3 days (Q3D)) induces significant tumor regression in the SMARCA4G12C-mutant LU11760 NSCLC PDX model[1].
PRT3789 (200 mg/kg; s.c.; every 3 days (Q3D)) induces significant tumor growth inhibition and near-complete SMARCA2 reduction (IHC H-score <10) in the CTG-3710 NSCLC PDX model[1].
PRT3789 (on days 1, 4, and 7) induces robust, selective degradation of SMARCA2 protein in PBMCs of healthy rats following dosing on days 1, 4, and 7[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude, NOD/SCID, athymic Nude-Foxn1nu (female, 6 to 9 weeks old, weighing >17-18 g, subcutaneous NCI-H1793 xenograft model)[1]
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Dosage:100 mg/kg
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Administration:s.c.; every 3 days (Q3D)
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Result:Induced tumor regression, with mean tumor volumes reduced to <50 mm3 by day 36 of dosing, compared with vehicle control mean tumor volumes >600 mm3.
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Animal Model:Immunocompromised (female, 6 to 9 weeks old, weighing >17-18 g, subcutaneous patient-derived xenograft model)[1]
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Dosage:100 mg/kg
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Administration:s.c.; once weekly
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Result:Induced tumor growth inhibition, with mean tumor volumes remaining <300 mm3 by day 60 of dosing, compared with vehicle control mean tumor volumes >1000 mm3.
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Animal Model:Immunocompromised (female, 6 to 9 weeks old, weighing >17-18 g, subcutaneous patient-derived xenograft model)[1]
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Dosage:200 mg/kg
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Administration:s.c.; every 3 days (Q3D)
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Result:Induced tumor regression, with mean tumor volumes reduced to <50 mm3 by day 32 of dosing, compared with vehicle control mean tumor volumes >700 mm3.\nInduced tumor growth inhibition, with mean tumor volumes remaining <500 mm3 by day 20 of dosing, compared with vehicle control mean tumor volumes >1500 mm3.
Reduced SMARCA2 IHC H-score from ~90 in vehicle controls to <10 in treated mice at study endpoint.
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. 2755761-78-3
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Appearance Solid
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Molecular Weight 891.09
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Formula C47H58N10O6S
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Color White to off-white
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SMILES
CC1=C(SC=N1)C2=CC=C(C=C2)[C@@H](NC([C@@H]3C[C@H](CN3C([C@H](C(C)C)C4=CC(O[C@@H](C)CN5CC[C@H](C5)N6CCN7C8=C(NC[C@H]7C6)N=NC(C9=C(C=CC=C9)O)=C8)=NO4)=O)O)=O)C
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 25 mg/mL (28.06 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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. 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. 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 (2.81 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 (2.81 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.
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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RT-PCR
Reverse transcription technology uses RNA as a template to synthesize DNA. RT-PCR is simple, specific and sensitive, and can be used to detect gene expression levels and expression differences in cells; detect RNA virus content; clone cDNA sequences of specific genes.
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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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Research Protocol for Epigenomic Data Analysis
Epigenomic data analysis identifies genome-wide regulatory features that influence gene expression, chromatin state, and phenotype without changing the underlying DNA sequence. In this strategy, the core regulatory layer includes chromatin accessibility, transcription-factor or histone-mark occupancy, DNA methylation, and chromatin-state patterns; these features are measured by sequencing-based assays and interpreted as regulatory elements, promoters, enhancers, repressive domains, methylated cytosines, or candidate phenotype-associated chromatin programs. The literature links epigenomic features to phenotype by showing that functional genomic elements can be mapped across human cell types and tissues, and that integrated epigenomic maps reveal cell-type-specific regulatory programs. ENCODE integrated transcription, chromatin accessibility, transcription-factor occupancy, and histone modification data to annotate functional elements in the human genome, while the Roadmap Epigenomics Co
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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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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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Soft Agar Colony Formation Assay
Soft agar colony formation assay measures anchorage-independent growth, in which transformed or tumorigenic cells proliferate as colonies in a semisolid agar matrix while many non-transformed adherent cells fail to proliferate without attachment; classic studies showed that growth in semisolid medium correlates with tumorigenicity in nude mice, and later protocol papers describe the method as a stringent in vitro assay for malignant transformation. The readout is the number, size, morphology, or signal intensity of colonies formed within agar after incubation; published formats include manual colony counting after staining, 96-well or 384-well quantitative formats, DNA-binding dye detection, MTT/tetrazolium-based detection, digital image analysis, and PCR-based marker detection from soft agar cultures.
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Colony Formation (Clonogenic) Assay
The clonogenic (colony formation) assay measures the ability of a single cell to retain reproductive viability and form a macroscopic colony, typically defined as a cluster derived from one progenitor cell after a defined growth period. This assay is widely used to evaluate cell survival after exposure to ionizing radiation or cytotoxic treatments and is considered a standard method in radiation biology for generating dose-response relationships of reproductive cell death. Colony formation reflects long-term proliferative capacity rather than short-term metabolic activity, and survival is quantified by comparing treated versus untreated conditions based on colony number and derived survival fractions.
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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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Real Time qPCR (Q-PCR)
Real-time quantitative PCR (qPCR) quantifies an amplifiable nucleic-acid target by monitoring fluorescence during PCR cycling rather than measuring product only after amplification. The increase in fluorescence tracks accumulation of PCR product, and the quantification cycle (Cq; historically also Ct/CP) is related to the initial amount of target: samples containing more starting target generally reach the defined fluorescence threshold in fewer cycles.
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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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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Purity & Documentation
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Data Sheet (281 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
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. 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 | 1.1222 mL | 5.6111 mL | 11.2222 mL | 28.0555 mL |
| 5 mM | 0.2244 mL | 1.1222 mL | 2.2444 mL | 5.6111 mL | |
| 10 mM | 0.1122 mL | 0.5611 mL | 1.1222 mL | 2.8056 mL | |
| 15 mM | 0.0748 mL | 0.3741 mL | 0.7481 mL | 1.8704 mL | |
| 20 mM | 0.0561 mL | 0.2806 mL | 0.5611 mL | 1.4028 mL | |
| 25 mM | 0.0449 mL | 0.2244 mL | 0.4489 mL | 1.1222 mL |
PRT3789 Related Classifications
HY-159607 Related Classifications
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