TNG456
TNG456 is an orally active, CNS-penetrant, selective, MTA-cooperative PRMT5 inhibitor. TNG456 drives dose-dependent antitumor activity in mouse xenograft models. TNG456 can be used for the research of MTAP-null solid tumors, including gliomas, and CNS metastases.
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- CAS. Nr.: 2962087-36-9
- Formel: C18H17F3N6O2
- Molecular Weight:406.36
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
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Chemical Information
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Biologische Aktivität
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PRMT5 |
TNG456 (10 μM) exhibits high selectivity for PRMT5, with no significant activity against 40 other methyltransferases when tested at 10 μM[2].
TNG456 (7 days) inhibits the viability of HAP1 MTAP-null cells with a GI50 of 20 nM, and is 50-fold more selective for HAP1 MTAP-null cells than HAP1 MTAP WT cells[2].
TNG456 (7 days) inhibits the viability of MTAP-null LU99, LN18, HCT116, and HAP1 cells with GI50 values ranging from 0.015 μM to 0.054 μM, and shows an average 55-fold selectivity over their matched MTAP WT counterparts[2].
TNG456 exhibits favorable metabolic stability in human liver microsomes, with an intrinsic clearance of 13 μL/min/mg[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | CL | Vdss | T1/2 | Cmax | AUCinf | Bioavailability |
|---|---|---|---|---|---|---|---|---|
| Dog[2] | 1 mg/kg | i.v. | 3.0 mL/min/kg | 1.5 L/kg | 6.4 h | / | / | / |
| Dog[2] | 3 mg/kg | p.o. | / | / | / | 0.802 μg/mL | 9.2 μg·h/mL | 55 % |
| Cynomolgus Monkey[2] | 1 mg/kg | i.v. | 16 mL/min/kg | 4.0 L/kg | 3.9 h | / | / | / |
| Cynomolgus Monkey[2] | 3 mg/kg | p.o. | / | / | / | 0.366 μg/mL | 2.55 μg·h/mL | 85 % |
TNG456 (30-90 mg/kg; p.o.; BID) exhibits potent, durable antitumor activity across diverse mouse MTAP-null patient-derived xenograft models[2].
TNG456 (45-90 mg/kg; p.o.; BID) in combination with Abemaciclib (HY-16297A) delivers robust antitumor benefit in aggressive MTAP-null glioblastoma xenografts[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 mice (female, 6 to 8 weeks old) subcutaneously inoculated with U87MG cells[2]
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Dosage:3; 10; 30; 90 mg/kg
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Administration:i.g.; BID; 7 days
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Result:Achieved greater than 90% inhibition of symmetric dimethylarginine (SDMA)-modified protein levels in tumors at doses ≥30 mg/kg BID.
Produced 84% tumor growth inhibition (TGI) at 30 mg/kg BID.
Induced 56% tumor regression at 90 mg/kg BID.
Showed no significant body weight loss across all doses.
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Animal Model:BALB/c nude mouse PDX models (bladder; cholangiocarcinoma; pancreatic; NSCLC; Glioblastoma)[2]
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Dosage:30; 60; 90 mg/kg
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Administration:p.o.; BID
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Result:Achieved 72-99% TGI in 5 of 13 MTAP-null patient-derived xenograft models.
Induced tumor shrinkage in 8 of 13 models, including complete and durable responses in non-small cell lung cancer (squamous) and glioblastoma models that persisted after treatment cessation.
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Animal Model:BALB/c nude mice (female, 6-8 weeks old) inoculated with AM38 cells or glioblastoma xenografts[2]
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Dosage:45; 90 mg/kg
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Administration:p.o.; BID
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Result:Reduced tumor growth in the AM38 CDX model when combined with 50 mg/kg QD Abemaciclib at 45 mg/kg BID.
Further suppressed tumor growth in the AM38 CDX model when combined with 20 mg/kg QD Abemaciclib at 90 mg/kg BID.
Prevented substantial tumor growth in the glioblastoma PDX model when combined with 50 mg/kg QD Abemaciclib at 45 mg/kg BID.
Induced complete responses in the glioblastoma PDX model when combined with 20 mg/kg QD Abemaciclib at 90 mg/kg BID.
Showed no significant toxicity across all treatments.
Chemical Information
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CAS. Nr. 2962087-36-9
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Molecular Weight 406.36
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Formel C18H17F3N6O2
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SMILES
CN([C@@H](C1=CC=C(C=C1)C(F)(F)F)C)C(C(NC2=C3NN=CC3=C(N=C2)N)=O)=O
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
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