2. Epigenetics
  3. Histone Methyltransferase
  4. 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.

For research use only. We do not sell to patients.

TNG456

TNG456 Chemical Structure

CAS No. : 2962087-36-9

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TNG456 Related Antibodies

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View All Histone Methyltransferase Isoform Specific Products:

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EZH1 EZH2 DOT1L SMYD2 SMYD3 SUV39H2/KMT1B EHMT2/G9a/KMT1C EHMT1/GLP/KMT1D ASH1L/KMT2H SETDB1/KMT2G SETD2/KMT3A NSD2/MMSET/WHSC1 NSD3/WHSC1L1 SETD7/KMT7 SETD8/KMT5A PRMT1 PRMT3 PRMT4 PRMT5 PRMT6 PRMT7 PRMT8

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Description

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[1][2].

IC50 & Target[1]

PRMT5

 

In Vitro

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.

TNG456 Related Antibodies
Parmacokinetics
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 %
In Vivo

TNG456 (3-90 mg/kg; p.o.; BID; 7 days) drives dose-dependent, on-target antitumor activity in mouse U87MG MTAP-null glioblastoma xenografts[2].
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.

Animal Model: BALB/c nude mice (female, 6 to 8 weeks old) subcutaneously inoculated with U87MG cells[2]
Dosage: 3; 10; 30; 90 mg/kg
Administration: i.g.; BID; 7 days
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.
Animal Model: BALB/c nude mouse PDX models (bladder; cholangiocarcinoma; pancreatic; NSCLC; Glioblastoma)[2]
Dosage: 30; 60; 90 mg/kg
Administration: p.o.; BID
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.
Animal Model: BALB/c nude mice (female, 6-8 weeks old) inoculated with AM38 cells or glioblastoma xenografts[2]
Dosage: 45; 90 mg/kg
Administration: p.o.; BID
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.
Molecular Weight

406.36

Formula

C18H17F3N6O2
CAS No.
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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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TNG456 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

TNG4562962087-36-9TNG 456TNG-456Histone Methyltransferasechronic myeloid leukemiagliomasPRMT5colorectal cancerdogsxenograft modelsnonsmall cell lung cancerglioblastomaMTAP-null cancer cellsnon-human primatesInhibitorinhibitorinhibit

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