WT161 Property

Density 

1.15±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMF: 10 mg/ml; DMSO: 10 mg/ml; DMSO:PBS (pH 7.2) (1:2): 0.33 mg/ml

form 

A crystalline solid

pka

9.48±0.20(Predicted)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P321Specific treatment (see … on this label).

P330Rinse mouth.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P405Store locked up.

P501Dispose of contents/container to..…

WT161 Chemical Properties,Usage,Production

Definition

ChEBI: LSM-6269 is a tertiary amine.

Biological Activity

WT161 is a potent and selective HDAC6 inhibitor with IC50 values of 0.4 nM, 8.35 nM and 15.4 nM for HDAC6, HDAC1 and HDAC2, respectively, which is more than 100-fold selective for other HDACs.

in vitro

WT161 can selectively inhibit HDAC6 and significantly increase the level of acetylated α-tubulin, with little effect on the overall lysine acetylation. It is able to induce accumulation and toxicity of acetylated tubulin in multiple myeloma cells. WT161 alone did not induce ER stress response, UPR, or ER stress-related apoptosis. In cultured MCL JeKo-1 and Z138 cells, treatment with WT-161 increased intracellular ubiquitinated protein levels. WT-161 dose-dependently depletes cyclin D1 levels in cultured MCL cells (mantle cell lymphoma). Treatment of WT-161 also induced ER stress response in MCL cells-GRP78 protein level, phosphorylated eIF2α level increased, and pro-apoptotic transcription factor CHOP was induced. WT161 induced apoptotic cell death in MCF7, T47D, BT474 and MDA-MB231 cells, and decreased the expression of EGFR, HER2, ERα and downstream signals.

in vivo

WT161 has a reasonable half-life (1.4 hours) and drug exposure (Cmax=18 mg/L) in mice. It was well tolerated when administered as a single agent. It significantly inhibited the growth of MCF7 cells in vivo and down-regulated the expression of ERα in a xenograft tumor mouse model.

target

< td style="border-bottom: 1px dotted #ccc;padding: 5px;"> HDAC2
(Cell-free assay)

Target	Value
HDAC6 (Cell-free assay)	0.4 nM
HDAC1 (Cell-free assay)	8.35 nM
15.4 nM