WT161

Catalog No.S8495 Batch:S849501

Print

Technical Data

Formula

C27H30N4O3
Molecular Weight 458.55 CAS No. 1206731-57-8
Solubility (25°C)* In vitro DMSO 86 mg/mL (187.54 mM)
Ethanol 1 mg/mL (2.18 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.

 4.3mg/ml (9.38mM) Taking the 1 mL working solution as an example, add 50 μL of 86 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
Clear solution
5% DMSO 95% Corn oil

Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.

 0.61mg/ml (1.33mM) Taking the 1 mL working solution as an example, add 50 μL of 12.2 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description WT161 is a potent, selective, and bioavailable HDAC6 inhibitor with IC50 values of 0.4 nM, 8.35 nM and 15.4 nM for HDAC6, HDAC1 and HDAC2, respectively; shown to have >100-fold selectivity over other HDACs. This compound induces apoptosis.
Targets
HDAC6 [1]
(Cell-free assay)		 HDAC1 [1]
(Cell-free assay)		 HDAC2 [1]
(Cell-free assay)
0.4 nM 8.35 nM 15.4 nM
In vitro

WT161 selectively inhibits HDAC6 and dramatically increases levels of acetylated α-tubulin (Ac-α-tubulin) with little effect on global lysine acetylation. It induces accumulation of acetylated tubulin and cytotoxicity in multiple myeloma (MM) cells. This compound as a single agent does not induce ER stress, the UPR, or ER stress-mediated apoptosis. Consistent with this compound mediated hyperacetylation and inhibition of hsp90 chaperone function, treatment with this chemical increases the intracellular levels of polyubiuitylated proteins in the cultured MCL JeKo-1 and Z138 cells. It also dose-dependently depletes the levels of cyclin D1 in the cultured human Mantle Cell Lymphoma (MCL) cells. Treatment with this agent induces ER stress response in the MCL cells, demonstrated by increase in the protein levels of Glucose regulated protein (GRP) 78, phosphorylated eIF2 (eukaryotic initation factor 2) α, and induction of the pro-apoptotic transcription factor CHOP (CAAT/Enhancer Binding Protein Homologous Protein). This compound triggers apoptotic cell death in MCF7, T47D, BT474, and MDA-MB231 cells, associated with decreased expression of EGFR, HER2, and ERα and downstream signaling.
In vivo

WT161 has reasonable half-life in mice (1.4 h) and drug exposure [maximum concentration (Cmax) = 18 mg/L]. It is well tolerated as a single agent. This compound significantly inhibits in vivo MCF7 cell growth, associated with downregulation of ERα, in a murine xenograft model.

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    MM.1S cells 

  • Concentrations

    3 µM

  • Incubation Time

    16 h

  • Method

    For annexin V-PI staining, MM.1S cells cultured for 16 h with BTZ (3 nM) and/or tubacin/WT161 (3 µM) are washed with PBS and processed.
Animal Study:

[3]
  • Animal Models

    Female NCr nu/nu mice subcutaneously (sc) implanted with 17β-estradiol-sustained release pellets and inoculated s.c. with 5 × 106 MCF-7 cells suspended in 30% Matrigel

  • Dosages

    80 mg/kg

  • Administration

    i.p.

References

  • https://pubmed.ncbi.nlm.nih.gov/27799547/
  • http://www.bloodjournal.org/content/116/21/2856?sso-checked=true
  • https://pubmed.ncbi.nlm.nih.gov/29113288/

Selleck's WT161 Has Been Cited by 4 Publications

In-Cell Testing of Zinc-Dependent Histone Deacetylase Inhibitors in the Presence of Class-Selective Fluorogenic Substrates: Potential and Limitations of the Method [ Biomedicines, 2024, 12(6)1203] PubMed: 38927410
Epigenetic and molecular coordination between HDAC2 and SMAD3-SKI regulates essential brain tumour stem cell characteristics [ Nat Commun, 2023, 14(1):5051] PubMed: 37598220
Incorporation of SKI-G-801, a Novel AXL Inhibitor, With Anti-PD-1 Plus Chemotherapy Improves Anti-Tumor Activity and Survival by Enhancing T Cell Immunity [ Front Pharmacol, 2022, 13:780179] PubMed: 35330829
NADPH levels affect cellular epigenetic state by inhibiting HDAC3-Ncor complex [ Nat Metab, 2021, 3(1):75-89] PubMed: 33462516

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.