Synonym
LMK235; LMK 235; LMK-235.
IUPAC/Chemical Name
N-((6-(hydroxyamino)-6-oxohexyl)oxy)-3,5-dimethylbenzamide
InChi Key
VRYZCEONIWEUAV-UHFFFAOYSA-N
InChi Code
InChI=1S/C15H22N2O4/c1-11-8-12(2)10-13(9-11)15(19)17-21-7-5-3-4-6-14(18)16-20/h8-10,20H,3-7H2,1-2H3,(H,16,18)(H,17,19)
SMILES Code
O=C(NOCCCCCC(NO)=O)C1=CC(C)=CC(C)=C1
Appearance
White to off-white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
LMK-235 is a potent and selective HDAC4/5 inhibitor, inhibits HDAC5, HDAC4, HDAC6, HDAC1, HDAC2, HDAC11 and HDAC8, with IC50s of 4.22 nM, 11.9 nM, 55.7 nM, 320 nM, 881 nM, 852 nM and 1278 nM, respectively.
In vitro activity:
It was found that LMK-235, a selective inhibitor of class IIA HDAC4/5, induced apoptosis of MM cells by downregulating HO-1 that is closely related to HDAC4. LMK-235 increased phosphorylation of JNK and c -Jun in MM cells. Downregulation of HO-1 expression in combination with LMK-235 expression further activated phosphorylation of JNK and c-Jun and induced apoptosis in MM cells. When the JNK inhibitor SP600125 was used in combination, the apoptosis phenomenon was reversed. However, when HO-1 was upregulated, LMK-235-mediated phosphorylation of JNK and c-Jun was inhibited, and apoptosis of MM cells began to decrease. These data suggest that LMK-235 has potent anti-myeloma activity through regulation of HO-1-induced apoptosis via the JNK/AP-1 pathway. This provides a new concept for the treatment of multiple myeloma.
Reference: Life Sci. 2019 Apr 15;223:146-157. https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(19)30169-9
In vivo activity:
The effects of 2 doses (5 and 20 mg/kg) of LMK235 on H3 acetylation were examined. It was found that an 8-day treatment with the lowest dose (5 mg/kg) was sufficient to fully restore H3 acetylation in the hippocampus of Cdkl5 -/Y mice (Fig. 7B). A moderate increase in H3 acetylation was also found in control mice (data not shown). Based on these results, Cdkl5 -/Y and control Cdkl5 +/Y male mice were treated daily with the lowest dose of LMK235 or vehicle. Some mice were sacrificed after 8 days of treatment. Other mice were treated for 8 days plus additional 8 days during which they were behaviorally tested. These mice were sacrificed immediately after behavioral testing (i.e. 16 days after initiation of treatment; Fig. 7A). The effects of treatment on the neuroanatomy of the hippocampal region were examined in mice treated for 8 and 16 days. It was found that both 8 and 16 days of treatment had no adverse effect on body weight in both genotypes indicating that LMK235 does not impair animals' well-being (Supplementary Material, Table 1).
Reference: Hum Mol Genet. 2016 Sep 15;25(18):3887-3907. https://academic.oup.com/hmg/article-lookup/doi/10.1093/hmg/ddw231
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
29.4 |
100.00 |
| Ethanol |
29.4 |
100.00 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
294.35
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
In vitro protocol:
1. Li X, Guo Y, Kuang X, Zhao L, Li H, Cheng B, Wang W, Zhang Z, Liu P, Wang J. Histone deacetylase inhibitor LMK-235-mediated HO-1 expression induces apoptosis in multiple myeloma cells via the JNK/AP-1 signaling pathway. Life Sci. 2019 Apr 15;223:146-157. doi: 10.1016/j.lfs.2019.03.011. Epub 2019 Mar 12. PMID: 30876940.
2. Li A, Liu Z, Li M, Zhou S, Xu Y, Xiao Y, Yang W. HDAC5, a potential therapeutic target and prognostic biomarker, promotes proliferation, invasion and migration in human breast cancer. Oncotarget. 2016 Jun 21;7(25):37966-37978. doi: 10.18632/oncotarget.9274. Erratum in: Oncotarget. 2017 May 2;8(18):30619-30620. PMID: 27177225; PMCID: PMC5122364.
In vivo protocol:
1. Trazzi S, Fuchs C, Viggiano R, De Franceschi M, Valli E, Jedynak P, Hansen FK, Perini G, Rimondini R, Kurz T, Bartesaghi R, Ciani E. HDAC4: a key factor underlying brain developmental alterations in CDKL5 disorder. Hum Mol Genet. 2016 Sep 15;25(18):3887-3907. doi: 10.1093/hmg/ddw231. Epub 2016 Jul 27. PMID: 27466189.
1: Hansen FK, Sumanadasa SD, Stenzel K, Duffy S, Meister S, Marek L, Schmetter R, Kuna K, Hamacher A, Mordmüller B, Kassack MU, Winzeler EA, Avery VM, Andrews KT, Kurz T. Discovery of HDAC inhibitors with potent activity against multiple malaria parasite life cycle stages. Eur J Med Chem. 2014 Jul 23;82:204-13. doi: 10.1016/j.ejmech.2014.05.050. Epub 2014 May 22. PubMed PMID: 24904967.
2: Marek L, Hamacher A, Hansen FK, Kuna K, Gohlke H, Kassack MU, Kurz T. Histone deacetylase (HDAC) inhibitors with a novel connecting unit linker region reveal a selectivity profile for HDAC4 and HDAC5 with improved activity against chemoresistant cancer cells. J Med Chem. 2013 Jan 24;56(2):427-36. doi: 10.1021/jm301254q. Epub 2013 Jan 8. PubMed PMID: 23252603.
