TNG456
Based on 1 Customer Validation
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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- Purity : 99.70%
- CAS No.: 2962087-36-9
- 화학식: C18H17F3N6O2
- 분자량:406.36
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보관:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from 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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용액&용해도
- Protocol
- 순도&문서
- References
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Help & FAQs
All Histone Methyltransferase Isoforms
More
Biological Activity
제품 설명
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.
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 (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 No. 2962087-36-9
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Appearance Powder
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분자량 406.36
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화학식 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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선적
Room temperature in continental US; may vary elsewhere.
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보관
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
용액&용해도
In Vitro:
DMSO : 100 mg/mL (246.09 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 (protect from 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 (protect from 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)
In Vivo:
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: ≥ 5 mg/mL (12.30 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 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: ≥ 5 mg/mL (12.30 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 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.
In Vivo Dissolution Calculator
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. * In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
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.
순도&문서
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Data Sheet (277 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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Handling Instructions (2659 KB)
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 (protect from 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 | 2.4609 mL | 12.3044 mL | 24.6087 mL | 61.5218 mL |
| 5 mM | 0.4922 mL | 2.4609 mL | 4.9217 mL | 12.3044 mL | |
| 10 mM | 0.2461 mL | 1.2304 mL | 2.4609 mL | 6.1522 mL | |
| 15 mM | 0.1641 mL | 0.8203 mL | 1.6406 mL | 4.1015 mL | |
| 20 mM | 0.1230 mL | 0.6152 mL | 1.2304 mL | 3.0761 mL | |
| 25 mM | 0.0984 mL | 0.4922 mL | 0.9843 mL | 2.4609 mL | |
| 30 mM | 0.0820 mL | 0.4101 mL | 0.8203 mL | 2.0507 mL | |
| 40 mM | 0.0615 mL | 0.3076 mL | 0.6152 mL | 1.5380 mL | |
| 50 mM | 0.0492 mL | 0.2461 mL | 0.4922 mL | 1.2304 mL | |
| 60 mM | 0.0410 mL | 0.2051 mL | 0.4101 mL | 1.0254 mL | |
| 80 mM | 0.0308 mL | 0.1538 mL | 0.3076 mL | 0.7690 mL | |
| 100 mM | 0.0246 mL | 0.1230 mL | 0.2461 mL | 0.6152 mL |
TNG456 Related Classifications
HY-183951 Related Classifications
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