| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
HDAC1 HDAC3
TNG260 targets the CoREST-HDAC1 complex, a specific histone deacetylase complex involved in transcriptional regulation. The compound selectively inhibits HDAC1 within the CoREST complex with 10-fold selectivity over HDAC3 and greater than 500-fold selectivity over other HDAC complexes including NuRD and Sin3. By inhibiting the CoREST-HDAC1 complex, TNG260 modulates gene expression and reverses immune resistance mechanisms. |
|---|---|
| ln Vitro |
In cell-free biochemical assays, TNG260 selectively inhibits HDAC1 activity with 10-fold selectivity over HDAC3. The compound exhibits greater than 500-fold selectivity for the CoREST complex over NuRD and Sin3 complexes. These in vitro activities demonstrate the compound's high selectivity for the CoREST-HDAC1 complex. The compound's inhibitory activity is measured using fluorogenic or radiometric HDAC activity assays with purified enzyme complexes.
|
| ln Vivo |
In cell-based assays, TNG260 inhibits HDAC1 with 10-fold selectivity over HDAC3. The compound causes HDAC1 inhibition and reverses anti-PD1 resistance driven by STK11 loss. TNG260 decreases intratumoral neutrophil infiltration and exhibits immune-mediated cell killing. The compound's effects on gene expression and immune cell function are evaluated in cell culture models of cancer.
|
| Enzyme Assay |
The cell-free HDAC inhibition assay typically involves incubation of purified HDAC complexes with a fluorogenic substrate and the inhibitor at various concentrations. The reaction is incubated at 37°C for 30-60 minutes, and fluorescence is measured to determine the degree of deacetylase activity inhibition. The selectivity for different HDAC complexes is determined by comparing IC50 values across HDAC1, HDAC3, NuRD, Sin3, and CoREST complexes.
|
| Cell Assay |
Cell-based assays for TNG260 involve culturing cancer cell lines with STK11 loss and treating them with the compound at concentrations ranging from 0.1 to 10 μM. Cells are incubated for 24-72 hours, and HDAC1 inhibition is assessed by measuring histone acetylation levels by Western blotting. The effect on anti-PD1 resistance reversal is evaluated by co-culture experiments with immune cells. Intratumoral neutrophil infiltration is assessed in cell models.
|
| Animal Protocol |
In animal models, TNG260 has been evaluated for its ability to inhibit CoREST-HDAC1 activity and reverse anti-PD1 resistance driven by STK11 loss. Typical studies involve oral administration of TNG260 to tumor-bearing mice at doses ranging from 10-100 mg/kg. The compound decreases intratumoral neutrophil infiltration and exhibits immune-mediated cell killing. Efficacy is assessed by tumor volume measurements, immune cell infiltration analysis, and survival studies.
|
| ADME/Pharmacokinetics |
TNG260 exhibits favorable pharmacokinetic properties including oral bioavailability. The compound is orally active and achieves therapeutic concentrations in tissues. Detailed pharmacokinetic parameters including plasma half-life, clearance, and volume of distribution have been reported. The compound's oral bioavailability supports its development as a therapeutic agent.
|
| Toxicity/Toxicokinetics |
Toxicity studies of TNG260 have been conducted as part of preclinical development. The compound is being evaluated for safety in animal models. As a HDAC inhibitor, potential toxicities include effects on normal tissues with high HDAC activity. Standard toxicology studies include assessment of target organ toxicity, hematological effects, and determination of maximum tolerated dose.
|
| References | |
| Additional Infomation |
TNG260 is an investigational drug being developed as a CoREST-selective deacetylase inhibitor for cancer immunotherapy. The compound is designed to reverse anti-PD1 resistance in STK11-mutant cancers. By inhibiting the CoREST-HDAC1 complex, TNG260 modulates the tumor immune microenvironment and enhances anti-tumor immune responses. The compound represents a novel approach to overcoming immune checkpoint inhibitor resistance. It is not yet approved for clinical use.
|
| Molecular Formula |
C20H18FN3O2S
|
|---|---|
| Molecular Weight |
383.43922662735
|
| Exact Mass |
383.11
|
| CAS # |
2935964-98-8
|
| Related CAS # |
(S)-TNG260;2935964-93-3
|
| PubChem CID |
168264922
|
| Appearance |
White to yellow solid powder
|
| LogP |
4.3
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
27
|
| Complexity |
621
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
N(C1=C(C=CC(C2C=CC(F)=CC=2)=C1)N)C(C1C=CC(S(=O)(=N)C)=CC=1)=O
|
| InChi Key |
JPFMYSJUFUEHBI-HHHXNRCGSA-N
|
| InChi Code |
InChI=1S/C20H18FN3O2S/c1-27(23,26)17-9-4-14(5-10-17)20(25)24-19-12-15(6-11-18(19)22)13-2-7-16(21)8-3-13/h2-12,23H,22H2,1H3,(H,24,25)/t27-/m1/s1
|
| Chemical Name |
N-[2-amino-5-(4-fluorophenyl)phenyl]-4-(methylsulfonimidoyl)benzamide
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6080 mL | 13.0398 mL | 26.0797 mL | |
| 5 mM | 0.5216 mL | 2.6080 mL | 5.2159 mL | |
| 10 mM | 0.2608 mL | 1.3040 mL | 2.6080 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
