| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
hHDAC6 36 nM (IC50)
HDAC6 (histone deacetylase 6). T‑518 is a selective, non‑hydroxamate, DFMO‑based HDAC6 inhibitor. |
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| ln Vitro |
In cell‑free enzymatic assays, T‑518 inhibits HDAC6 with an IC₅0 of 36 nM for human HDAC6. It is a selective HDAC6 inhibitor. In cellular assays, T‑518 increases acetylation of alpha‑tubulin (the primary substrate of HDAC6) and improves axonal transport. The compound is BBB‑permeable, making it suitable for central nervous system applications.
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| ln Vivo |
T‑518 has been shown to improve axonal transport in cellular models and has the potential to modulate tau pathology in vivo. As a BBB‑permeable HDAC6 inhibitor, it can be used in research on tauopathy and other neurodegenerative diseases. HDAC6 inhibition may reduce tau aggregation and improve the clearance of pathological tau species.
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| Enzyme Assay |
A general cell‑free protocol for HDAC6 inhibition is used as described for SE‑7552 (see V88666 field 5). Recombinant human HDAC6 enzyme (10‑50 nM) is incubated with a fluorogenic acetylated peptide substrate (Boc‑Lys(Ac)-AMC, 50 uM) in assay buffer (50 mM Tris‑HCl, pH 8.0, 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2, 1 mg/mL BSA) with varying concentrations of T‑518 (0.01 nM to 10 uM) at 37degC for 30 minutes. The reaction is stopped with developer solution containing trypsin. The AMC fluorescence is measured (excitation 380 nm, emission 460 nm). The IC₅0 (36 nM) is calculated. For selectivity profiling, T‑518 is tested against a panel of 11 HDAC isozymes.
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| Cell Assay |
A general cellular protocol for BBB‑permeable HDAC6 inhibitors: Primary neurons (e.g., rat cortical neurons or human iPSC‑derived neurons) are seeded in 12‑well plates. Cells are treated with T‑518 at concentrations of 0.01‑10 uM for 24‑48 hours. For assessment of alpha‑tubulin acetylation, cells are lysed and subjected to Western blot with anti‑acetyl‑alpha‑tubulin (Lys40) and anti‑total‑alpha‑tubulin antibodies. For axonal transport assays, neurons are cultured in microfluidic chambers, and the transport of fluorescently labeled vesicles (e.g., mitochondria labeled with MitoTracker) is tracked by live‑cell imaging. The rate and distance of axonal transport are quantified. For tauopathy models, neurons expressing mutant tau (e.g., P301L tau) are treated with T‑518, and tau acetylation, tau aggregation, and cell viability are assessed.
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| Animal Protocol |
A general animal protocol for T‑518 in a tauopathy model: Male transgenic mice expressing mutant human tau (e.g., P301S mice (PS19 line) or rTg4510 mice) are used as a model of tauopathy and Alzheimer‘s disease. At 3‑6 months of age, before the onset of significant tau pathology, mice are randomized into treatment groups (n=10‑12 per group). T‑518 is formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween‑80, 45% saline) and administered via oral gavage at doses of 3, 10, and 30 mg/kg once daily for 3‑6 months. Alternatively, for acute studies, T‑518 can be administered intraperitoneally (IP) at 10 mg/kg. At the end of the study, mice are euthanized, and brain and spinal cord tissues are harvested. Tau pathology is assessed by IHC (anti‑phospho‑tau antibodies: AT8, AT180, PHF1), biochemical fractionation (sarkosyl‑insoluble tau), and ELISA (total tau, phospho‑tau). Acetylated alpha‑tubulin levels are measured by Western blot. Axonal integrity is assessed by IHC for neurofilament proteins. Behavioral tests (Morris water maze, Y‑maze, rotarod) are performed to assess cognitive and motor function.
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| ADME/Pharmacokinetics |
General PK protocol for T‑518: Male Sprague‑Dawley rats are administered T‑518 via oral gavage (PO, 10 mg/kg) and intravenous (IV, 2 mg/kg). Blood samples are collected at 0.083, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours. Additionally, brain tissue is collected at selected time points to assess the brain‑to‑plasma ratio (Kp). Plasma and brain homogenate concentrations are quantified by LC‑MS/MS. PK parameters (Cmax, Tmax, AUC, t½, clearance, Vd, oral bioavailability, Kp) are calculated. The compound is BBB‑permeable, so significant brain exposure is expected.
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| Toxicity/Toxicokinetics |
General toxicity protocol for T‑518: A 28‑day repeat‑dose oral toxicity study is performed in Sprague‑Dawley rats. T‑518 is administered via oral gavage at doses of 5, 15, and 50 mg/kg/day for 28 days. Parameters include clinical signs, body weight, food consumption, functional observation battery (neurobehavioral assessment), hematology (complete blood count, differential), serum chemistry (ALT, AST, BUN, creatinine, CK), and histopathology of major organs with special attention to the brain, spinal cord, peripheral nerves, and muscle. Because HDAC6 is involved in immune function, potential effects on the spleen and thymus are also examined.
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| References |
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| Additional Infomation |
HDAC6 is a class IIb deacetylase that primarily deacetylates alpha‑tubulin, tau, and other cytoplasmic proteins. Inhibition of HDAC6 increases alpha‑tubulin acetylation, which enhances microtubule stability and axonal transport. In tauopathies (including Alzheimer‘s disease), HDAC6 is upregulated and contributes to tau hyperphosphorylation and aggregation. T‑518 is a DFMO‑based non‑hydroxamate HDAC6 inhibitor with an IC₅0 of 36 nM. The molecular formula is C1₉H1₆F₇N₅O3, and the molecular weight is 495.35 g/mol. The compound is stored at -20degC as a powder. For research use only; not for human use.
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| Molecular Formula |
C19H16F7N5O3
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|---|---|
| Molecular Weight |
495.35
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| Exact Mass |
495.114
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| CAS # |
2276680-91-0
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| PubChem CID |
137472644
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| Appearance |
White to off-white solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
34
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| Complexity |
786
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| Defined Atom Stereocenter Count |
2
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| SMILES |
FC(C(F)(F)F)(C(N[C@@H]1CCCC[C@H]1N1C(C2=CC(C3=NN=C(C(F)F)O3)=CN=C2C1)=O)=O)F
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| InChi Key |
OTPOPNFYEGYICX-ZYHUDNBSSA-N
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| InChi Code |
InChI=1S/C19H16F7N5O3/c20-13(21)15-30-29-14(34-15)8-5-9-11(27-6-8)7-31(16(9)32)12-4-2-1-3-10(12)28-17(33)18(22,23)19(24,25)26/h5-6,10,12-13H,1-4,7H2,(H,28,33)/t10-,12-/m1/s1
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| Chemical Name |
N-[(1R,2R)-2-[3-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-5-oxo-7H-pyrrolo[3,4-b]pyridin-6-yl]cyclohexyl]-2,2,3,3,3-pentafluoropropanamide
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0188 mL | 10.0939 mL | 20.1877 mL | |
| 5 mM | 0.4038 mL | 2.0188 mL | 4.0375 mL | |
| 10 mM | 0.2019 mL | 1.0094 mL | 2.0188 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.
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