PRT3789 trihydrochloride
Based on 1 Customer Validation
PRT3789 (trihydrochloride) is a selective SMARCA2 PROTAC degrader (DC50 in HeLa cell: 0.72 nM for SMARCA2, 14 nM for SMARCA4). PRT3789 (trihydrochloride) 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 (trihydrochloride) 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 (trihydrochloride) induces synthetic lethality, inhibits proliferation and colony formation, and drives tumor growth inhibition and regression in SMARCA4-deficient contexts. PRT3789 (trihydrochloride) 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.
- Formula: C47H61Cl3N10O6S
- Molecular Weight:1000.47
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Storage:
4°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
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
Biological Activity
Description
IC50 & Target
[1]|
SMARCA2 0.72 nM (DC50) |
SMARCA4 14 nM (DC50) |
In Vitro
PRT3789 hydrochloride 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) hydrochloride 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 hydrochloride 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) hydrochloride 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) hydrochloride 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) hydrochloride 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.
In Vivo
PRT3789 (100 mg/kg; s.c.; once weekly) hydrochloride 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)) hydrochloride 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)) hydrochloride induces significant tumor regression in the SMARCA4G12C-mutant LU11760 NSCLC PDX model[1].
PRT3789 (200 mg/kg; s.c.; every 3 days (Q3D)) hydrochloride 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) hydrochloride 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.
- RT-PCR
- RNA extraction experimental
- Research Protocol for Epigenomic Data Analysis
- Patient-Derived Xenograft (PDX)
- Patient-Derived Orthotopic Xenograft (PDOX)
- Soft Agar Colony Formation Assay
- Colony Formation (Clonogenic) Assay
- Subcutaneous Cell-Line-Derived Xenograft
- Real Time qPCR (Q-PCR)
- Orthotopic Cell-Line Xenograft
- Cell Viability Determination by MTT Colorimetric Assay
Chemical Information
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Appearance Solid
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Molecular Weight 1000.47
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Formula C47H61Cl3N10O6S
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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.Cl.Cl.Cl
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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 and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
Solvent & Solubility
In Vitro:
DMSO : ≥ 100 mg/mL (99.95 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 and light). 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 and light). 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)
Purity & Documentation
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 (sealed storage, away from moisture and light). 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 | 0.9995 mL | 4.9977 mL | 9.9953 mL | 24.9883 mL |
| 5 mM | 0.1999 mL | 0.9995 mL | 1.9991 mL | 4.9977 mL | |
| 10 mM | 0.1000 mL | 0.4998 mL | 0.9995 mL | 2.4988 mL | |
| 15 mM | 0.0666 mL | 0.3332 mL | 0.6664 mL | 1.6659 mL | |
| 20 mM | 0.0500 mL | 0.2499 mL | 0.4998 mL | 1.2494 mL | |
| 25 mM | 0.0400 mL | 0.1999 mL | 0.3998 mL | 0.9995 mL | |
| 30 mM | 0.0333 mL | 0.1666 mL | 0.3332 mL | 0.8329 mL | |
| 40 mM | 0.0250 mL | 0.1249 mL | 0.2499 mL | 0.6247 mL | |
| 50 mM | 0.0200 mL | 0.1000 mL | 0.1999 mL | 0.4998 mL | |
| 60 mM | 0.0167 mL | 0.0833 mL | 0.1666 mL | 0.4165 mL | |
| 80 mM | 0.0125 mL | 0.0625 mL | 0.1249 mL | 0.3124 mL |
PRT3789 trihydrochloride Related Classifications
HY-159607B Related Classifications
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