PRMT5-IN-56
PRMT5-IN-56 is a PRMT5⋅MTA complex inhibitor with an IC50 of 0.2 nM, oral activity, and blood-brain barrier penetration. PRMT5-IN-56 inhibits PRMT5 methyltransferase activity in an MTA-cooperative manner, suppresses symmetrical dimethylarginine levels in MTAP-deficient cells. PRMT5-IN-56 suppresses proliferation of MTAP-deleted cancer cells with high selectivity over MTAP-wild type cells. PRMT5-IN-56 induces dose-dependent tumor growth inhibition in subcutaneous xenograft models, inhibits intracranial tumor progression, and prolongs survival in orthotopic brain xenograft models. PRMT5-IN-56 exhibits high intrinsic permeability, good oral bioavailability, and a high brain-to-plasma ratio. PRMT5-IN-56 can be used for the research of MTAP-deleted cancers and glioblastoma.
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- CAS No.: 3062852-59-6
- Formule: C25H24F3N5O2
- Masse moléculaire:483.49
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
IC50 & Target
[1]|
PRMT5 |
In Vitro
PRMT5-IN-56 (compound 21) (6 days) potently and selectively inhibits the proliferation of MTAP-deleted HCT116 cells with an IC50 of 1.1 nM, showing 214-fold selectivity over MTAP-wild type HCT116 cells[1].
PRMT5-IN-56 potently and selectively reduces symmetrical dimethylarginine (SDMA) levels in a concentration- and time-dependent manner in MTAP-deleted HCT116, LN18, and U87MG cells, with more rapid and profound effects than TNG462 (HY-156680) in glioma cell lines[1].
PRMT5-IN-56 (10 μM; 95 min) exhibits high intrinsic membrane permeability with a Papp of 16.94 × 10-6 cm/s and a low efflux ratio of 1.12 in a Caco-2 cell assay[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
| Species | Dose | Route | T1/2 | Vss | CL | AUClast | Tmax | Cmax | F | Plasma Concentration | Brain Concentration |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 3 mg/kg | i.v. | 0.42 h | 3229 mL/kg | 107 mL/min/kg | 476 ng·h/mL | / | / | / | / | / |
| Mice[1] | 30 mg/kg | p.o. | 0.90 h | / | / | 5119 ng·h/mL | 1.33 h | 1324 ng/mL | 108 % | / | / |
| Rat[1] | 2 mg/kg | i.v. | 0.72 h | 4143 mL/kg | 66.0 mL/min/kg | 531 mL/kg | / | / | / | / | / |
| Rat[1] | 10 mg/kg | p.o. | 1.95 h | / | / | 1997 ng·h/mL | 1.00 h | 785 ng/mL | 75.3 % | / | / |
| Mice[1] | 30 mg/kg | p.o. | / | / | / | / | / | / | / | 2010 ng/mL | 1636 ng/g |
In Vivo
PRMT5-IN-56 (30-60 mg/kg; p.o.; daily; 36 days) induces dose-dependent tumor growth inhibition in MTAP-deleted U87MG orthotopic brain xenografts[1].
PRMT5-IN-56 (compound 21) (30-50 mg/kg; p.o.; daily; 14 days) induces dose-dependent tumor growth inhibition in MTAP-deleted HCT116 subcutaneous xenografts[1].
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 mice (female, 6 weeks old, subcutaneous xenograft model using MTAP-deleted HCT116 cells)[1]
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Dosage:30 mg/kg; 50 mg/kg
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Administration:p.o.; daily; 14 days
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Result:Achieved a tumor growth inhibition (TGI) rate of 74.1% at 30 mg/kg.
Achieved a TGI rate of 84.6% at 50 mg/kg, with complete tumor regression observed in 2 mice.
Caused no significant body weight loss.
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Animal Model:BALB/c nude mice (female, 6 weeks old, subcutaneous xenograft model using MTAP-deleted U87MG cells)[1]
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Dosage:10 mg/kg; 50 mg/kg
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Administration:p.o.; daily; 7 days
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Result:Achieved a TGI rate of 108.1% at 10 mg/kg.
Achieved a TGI rate of 138.6% at 50 mg/kg, with sustained tumor regression observed and tumor growth inhibition remaining stable after treatment discontinuation.
Caused no obvious body weight loss.
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Animal Model:BALB/c nude mice (female, 6 weeks old, orthotopic brain xenograft model using luciferase-expressing MTAP-deleted U87MG-luc cells)[1]
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Dosage:30 mg/kg; 60 mg/kg
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Administration:p.o.; daily; 36 days
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Result:Achieved a TGI rate of 87.75% and prolonged median survival to 45 days at 30 mg/kg.
Achieved a TGI rate of 98.96% (nearly abolishing detectable tumor signals) and prolonged median survival to >62 days at 60 mg/kg.
Caused no overt toxicity.
- How to Select the Route of Administration for Mammals
- Patient-Derived Xenograft (PDX)
- Protocol for Pharmacokinetic Study
- Patient-Derived Orthotopic Xenograft (PDOX)
- Transepithelial/transendothelial electrical resistance assay
- Splenic/Portal-Vein Liver Metastasis Xenograft
- Subcutaneous Cell-Line-Derived Xenograft
- Orthotopic Cell-Line Xenograft
- Cell Viability Determination by MTT Colorimetric Assay
- Intraperitoneal/Peritoneal Dissemination Xenograft
Chemical Information
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CAS No. 3062852-59-6
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Masse moléculaire 483.49
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Formule C25H24F3N5O2
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SMILES
CC1=CC(NC(C(N([C@@H]2CCCC3=CC=CC=C32)CC4=NC=C(C=C4)C(F)(F)F)=O)=O)=CN=C1N
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PRMT5-IN-56 Related Classifications
HY-184290 Related Classifications
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