PRT3789
Based on 1 Customer Validation
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).
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Pureté: 98.08%
- CAS No.: 2755761-78-3
- Formule: C47H58N10O6S
- Masse moléculaire:891.09
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Stockage:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
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SMARCA2 0.72 nM (DC50) |
SMARCA4 14 nM (DC50) |
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.
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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.
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.
| 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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Masse moléculaire 891.09
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Formule 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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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
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)
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.
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.
Pureté et documentation
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Fiche technique (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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Instruction de manipulation (2659 KB)
Références
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 |
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| 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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