Nexturastat A | CAS#1403783-31-2 | HDAC6 inhibitor

MedKoo Cat#: 406549 | Name: Nexturastat A

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Nexturastat A is an aryl urea derivative that acts as a potent and highly selective inhibitor of histone deacetylase 6 (HDAC6) (IC50= 5.02 +/- 0.60 nM). Nexturastat A possesses antiproliferative effects against melanoma cells. Histone deacetylases (HDACs) mediate regulation of gene expression via changes in nucleosome conformation. Dysregulation of histone acetylation can lead to the development of cancers. There is renewed interest in capitalizing new breakthroughs in epigenetic research to address oncology therapy.

Chemical Structure

Nexturastat A

CAS#1403783-31-2

Theoretical Analysis

MedKoo Cat#: 406549

Name: Nexturastat A

CAS#: 1403783-31-2

Chemical Formula: C19H23N3O3

Exact Mass: 341.1739

Molecular Weight: 341.40

Elemental Analysis: C, 66.84; H, 6.79; N, 12.31; O, 14.06

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship

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Synonym

Nexturastat A

IUPAC/Chemical Name

4-((1-butyl-3-phenylureido)methyl)-N-hydroxybenzamide

InChi Key

JZWXMCPARMXZQV-UHFFFAOYSA-N

InChi Code

InChI=1S/C19H23N3O3/c1-2-3-13-22(19(24)20-17-7-5-4-6-8-17)14-15-9-11-16(12-10-15)18(23)21-25/h4-12,25H,2-3,13-14H2,1H3,(H,20,24)(H,21,23)

SMILES Code

O=C(NO)C1=CC=C(CN(CCCC)C(NC2=CC=CC=C2)=O)C=C1

Appearance

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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#BBC70111

QC Data

View QC data: current batch, Lot#BBC70111

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Nexturastat A is a HDAC6 inhibitor with IC50 of 5 nM.

In vitro activity:

To figure out the internal molecular mechanism of NexA (Nexturastat A)-inducing apoptosis of MM (multiple myeloma) cells, the expression levels of apoptosis-related factors were estimated utilizing real-time PCR. The results showed that the p21 mRNA levels were higher in RPMI-8226 and U266 cells treated for 48 h (Figure 4A,B). Then Western blot assay manifested that NexA treatment also resulted in evident increases in p21 protein levels in both cell lines (Figure 4C). After which this study carried out p21 luciferase reporter gene assays to determine whether NexA could enhance the promoter activity of p21 accordingly. The data indicated the enhanced activity of p21 with 5 and 10 µM NexA for both cell lines (Figure 4D,E). This study also evaluated p21 induction in RPMI8226/BTZ100 cells. As shown in Figure 4C, F, p21 mRNA and protein levels increased after cells were treated with 20 µM NexA. This study observed enhanced p21 promoter activity in RPMI8226/BTZ100 cells treated with 3 and 5 µM NexA (Figure 4G). Reference: Biosci Rep. 2019 Mar 29; 39(3): BSR20181916. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430725/

In vivo activity:

This study observed a slight increase in the tumor infiltration of NK cells upon treatment with NextA (Nexturastat A) across all in vivo experiments. Therefore, this study wanted to investigate whether the inhibition of HDAC6 was able to modify the phenotype of these immune cells. Fresh NK cells were harvested from non-tumor bearing wild type C57BL/6 mice and treated with NextA to investigate the reported markers for NK cell activity and cytotoxicity, such as Granzyme B, TRAIL, and Fas ligand. Although this study observed an enhanced tumor infiltration of NK cells in all in vivo conditions using NextA, the aforementioned activation markers were minimally affected in isolated NK cells treated with this drug (Fig. 5A), suggesting that the enhanced NK infiltration observed after NextA treatment could be mediated by other indirect mechanisms. Reference: Sci Rep. 2019; 9: 6136. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467894/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	15.0	43.90

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 341.40 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

Formulation protocol:

1. Sun X, Xie Y, Sun X, Yao Y, Li H, Li Z, Yao R, Xu K. The selective HDAC6 inhibitor Nexturastat A induces apoptosis, overcomes drug resistance and inhibits tumor growth in multiple myeloma. Biosci Rep. 2019 Mar 22;39(3):BSR20181916. doi: 10.1042/BSR20181916. PMID: 30782785; PMCID: PMC6430725. 2. Knox T, Sahakian E, Banik D, Hadley M, Palmer E, Noonepalle S, Kim J, Powers J, Gracia-Hernandez M, Oliveira V, Cheng F, Chen J, Barinka C, Pinilla-Ibarz J, Lee NH, Kozikowski A, Villagra A. Selective HDAC6 inhibitors improve anti-PD-1 immune checkpoint blockade therapy by decreasing the anti-inflammatory phenotype of macrophages and down-regulation of immunosuppressive proteins in tumor cells. Sci Rep. 2019 Apr 16;9(1):6136. doi: 10.1038/s41598-019-42237-3. Erratum in: Sci Rep. 2019 Oct 10;9(1):14824. PMID: 30992475; PMCID: PMC6467894.

In vitro protocol:

In vivo protocol:

1. Knox T, Sahakian E, Banik D, Hadley M, Palmer E, Noonepalle S, Kim J, Powers J, Gracia-Hernandez M, Oliveira V, Cheng F, Chen J, Barinka C, Pinilla-Ibarz J, Lee NH, Kozikowski A, Villagra A. Selective HDAC6 inhibitors improve anti-PD-1 immune checkpoint blockade therapy by decreasing the anti-inflammatory phenotype of macrophages and down-regulation of immunosuppressive proteins in tumor cells. Sci Rep. 2019 Apr 16;9(1):6136. doi: 10.1038/s41598-019-42237-3. Erratum in: Sci Rep. 2019 Oct 10;9(1):14824. PMID: 30992475; PMCID: PMC6467894.

1: Bergman JA, Woan K, Perez-Villarroel P, Villagra A, Sotomayor EM, Kozikowski AP. Selective histone deacetylase 6 inhibitors bearing substituted urea linkers inhibit melanoma cell growth. J Med Chem. 2012 Nov 26;55(22):9891-9. doi: 10.1021/jm301098e. Epub 2012 Oct 23. PubMed PMID: 23009203; PubMed Central PMCID: PMC3562128.