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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
WT-161 (WT161) is a potent, selective and orally bioavailable HDAC6 inhibitor with IC50 value of 0.40 nM. WT161 has little to no effect on global lysine acetylation, but it selectively inhibits HDAC6 and dramatically raises acetylated α-tubulin levels. In multiple myeloma (MM) cells, WT-161 causes acetylated tubulin accumulation and cytotoxicity. WT161 does not trigger the UPR, ER stress, or ER stress-mediated apoptosis on its own. In cultured MCL JeKo-1 and Z138 cells, treatment with WT-161 increases the intracellular levels of polyubiquitylated proteins, which is consistent with WT-161 mediated hyperacetylation and inhibition of hsp90 chaperone function.
| Targets |
HDAC6 (IC50 = 0.4 nM); HDAC1 (IC50 = 8.35 nM); HDAC2 (IC50 = 15.4 nM); HDAC3 (IC50 = 51.6 nM); HDAC8 (IC50 = 1430 nM)
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| ln Vitro |
WT161 has little effect on global lysine acetylation but selectively inhibits HDAC6 and dramatically increases levels of acetylated α-tubulin (Ac-α-tubulin). With IC50s ranging from 1.5 to 4.7 µM, WT161 exhibits significant toxicity in every multiple myeloma cell line tested. Combining WT161 with bortezomib causes a marked build-up of polyubiquitinated proteins as well as cell stress, which in turn causes caspase activation and apoptosis. More significantly, it has been demonstrated that bone marrow stromal cells, which have been implicated in mediating multiple myeloma cell drug resistance, and bortezomib-resistant cells both respond well to this combination treatment[1].
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| ln Vivo |
WT161 is well tolerated at 50 mg/kg i.p., but it exhibits toxicity at 100 mg/kg i.p. WT161 and bortezomib together show a strong antitumor effect[1].
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| Enzyme Assay |
WT161 is an oral bioavailable, 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; it has been demonstrated to have selectivity over other HDACs that is >100-fold.
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| Cell Assay |
WT161 (0–10 μM) is added in increasing concentrations to MM.1S cells for a 48-hour period. Using the MTT assay, cell viability is assessed[1].
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| Animal Protocol |
Mice: The tumor xenograft mice are divided into cohorts that receive BTZ (0.5 mg/kg, i.v. ), WT161 (50 mg/kg, i.p. ), BTZ+WT161, or vehicle (control). Twice weekly, BTZ is administered, while WT161 is given for five days in a row. Estimating the tumor volume involves measuring the longest perpendicular tumor diameters with a calibre on alternate days[1].
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| References | |
| Additional Infomation |
LSM-6269 is a tertiary amine.
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| Molecular Formula |
C₂₇H₃₀N₄O₃
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|---|---|---|
| Molecular Weight |
458.55
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| Exact Mass |
458.231
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| Elemental Analysis |
C, 70.72; H, 6.59; N, 12.22; O, 10.47
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| CAS # |
1206731-57-8
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| Related CAS # |
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| PubChem CID |
44601455
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Index of Refraction |
1.594
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| LogP |
5.34
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
34
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| Complexity |
603
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(N/N=C/C1=CC=C(N(C2=CC=CC=C2)C3=CC=CC=C3)C=C1)CCCCCCC(NO)=O
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| InChi Key |
KXWWYFKVBFUVIZ-SGWCAAJKSA-N
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| InChi Code |
InChI=1S/C27H30N4O3/c32-26(15-9-1-2-10-16-27(33)30-34)29-28-21-22-17-19-25(20-18-22)31(23-11-5-3-6-12-23)24-13-7-4-8-14-24/h3-8,11-14,17-21,34H,1-2,9-10,15-16H2,(H,29,32)(H,30,33)/b28-21+
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| Chemical Name |
N'-hydroxy-N-[(E)-[4-(N-phenylanilino)phenyl]methylideneamino]octanediamide
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.45 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1808 mL | 10.9039 mL | 21.8079 mL | |
| 5 mM | 0.4362 mL | 2.1808 mL | 4.3616 mL | |
| 10 mM | 0.2181 mL | 1.0904 mL | 2.1808 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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