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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
(S)-TNG260 primarily targets the CoREST complex, specifically histone deacetylase 1 (HDAC1) within this complex. It inhibits HDAC1 with a 10-fold selectivity over the closely related HDAC3. The compound binds to the HDAC1 enzyme, modulating its deacetylase activity and thereby affecting gene expression. It has an IC50 of approximately 3 nM for HDAC1 inhibition.
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| ln Vitro |
In vitro studies show that TNG260, the racemate, causes HDAC1 inhibition and reverses anti-PD1 resistance driven by STK11 deletion. It also reduces intratumoral infiltration of neutrophils and exhibits immune-mediated cell killing. The selectivity of TNG260 leads to a unique gene expression signature distinct from that produced by pan-HDAC inhibitors, contributing to its anticancer effects.
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| ln Vivo |
In vivo, TNG260 has been shown to reverse anti-PD1 resistance in syngeneic mouse tumor models harboring STK11 deletion. By inhibiting HDAC1, the compound reactivates transposable elements and triggers an innate immune response via the STING pathway, leading to immune-mediated tumor cell killing. This demonstrates the potential of CoREST-selective HDAC1 inhibitors for overcoming immunotherapy resistance.
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| Enzyme Assay |
For cell-free assays, HDAC activity is typically measured using a fluorometric or luminescent HDAC assay kit. The assay involves incubating a purified HDAC enzyme (e.g., HDAC1) with a fluorogenic acetylated peptide substrate. After deacetylation by the enzyme, a developer is added to generate a fluorescent signal proportional to HDAC activity. The compound is added to the reaction to determine its IC50 by assessing the reduction in fluorescence.
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| Cell Assay |
In cellular studies, immune cells or cancer cells with STK11 deletion are cultured in a 96-well plate. The compound is added at various concentrations. The readouts include cell viability (MTT assay), target engagement (HDAC inhibition by Western blot for acetylated histone H3K9/K14), and immune-mediated cell killing assays in co-cultures with immune cells. Gene expression changes are analyzed by RT-qPCR or RNA-seq.
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| Animal Protocol |
To study tumor resistance reversal, mice bearing xenografts of cancer cells with STK11 deletion are treated with anti-PD1 antibodies alone or in combination with TNG260. The tumor volume is measured regularly, and the animals are euthanized at a pre-determined endpoint. Tumors are harvested for immunohistochemistry (IHC) analysis to assess immune cell infiltration, and peripheral blood is collected for T-cell profiling.
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| ADME/Pharmacokinetics |
The pharmacokinetic (PK) properties of the parent compound TNG260 have been investigated. It is an orally bioavailable compound. In preclinical species, TNG260 shows a short half-life, moderate clearance, and moderate volume of distribution. These properties are essential for its in vivo efficacy studies, where it is typically administered orally once or twice daily.
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| Toxicity/Toxicokinetics |
Preclinical toxicology data for (S)-TNG260 is not extensively detailed in the provided literature. However, as a selective HDAC inhibitor, its toxicity profile is expected to be less severe than that of non-selective pan-HDAC inhibitors, which are known to cause gastrointestinal distress and hematological toxicities. The compound is typically described as well-tolerated in mice at efficacious doses.
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| References |
[1]. Ahronian L, et al. TNG260, a CoREST-selective deacetylase inhibitor, reverses anti-PD1 resistance driven by loss of STK11[J]. J Immunother, 2022, 10(2): A1-A1595.
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| Additional Infomation |
TNG260 is a first-in-class, CoREST-selective deacetylase (CoreDAC) inhibitor. It represents a novel approach to cancer immunotherapy by reversing anti-PD1 resistance specifically driven by STK11 deletion. The compound downregulates the expression of HDAC1-controlled genes and activates the innate immune system through the STING pathway, leading to a reduction in immunosuppressive neutrophils in the tumor microenvironment. It is in preclinical research and has not yet advanced to clinical trials.
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| CAS # |
2935964-93-3
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| Related CAS # |
TNG260;2935964-98-8
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| Appearance |
Off-white to light yellow solid powder
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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
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| 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.) |
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.
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