CXD101 free base | CAS# 934828-12-3 | Inhibition

MedKoo Cat#: 581056 | Name: CXD101 free base

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Description:

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

CXD101, laos known as AZD-9468, is a novel histone deacetylase (HDAC) inhibitor. CXD101 is also known as HDAC-IN-4, is a histone deacetylase (HDAC) inhibitor. CXD101 inhibits the catalytic activity of HDAC, which results in an accumulation of highly acetylated histones, followed by the induction of chromatin remodeling and an altered pattern of gene expression. HDAC, a family of enzymes upregulated in many tumor types, deacetylates chromatin-associated histone proteins.

Chemical Structure

CXD101 free base

CAS#934828-12-3 (free base)

Theoretical Analysis

MedKoo Cat#: 581056

Name: CXD101 free base

CAS#: 934828-12-3 (free base)

Chemical Formula: C24H29N5O

Exact Mass: 403.2372

Molecular Weight: 403.53

Elemental Analysis: C, 71.44; H, 7.24; N, 17.36; O, 3.96

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 550.00	Ready to ship
50mg	USD 950.00	Ready to ship
100mg	USD 1,650.00	Ready to ship

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Related CAS #

934828-12-3 (free base) CXD101 HCl

Synonym

CXD101; CXD-101; CXD 101; AZD9468; AZD-9468; AZD 9468; HDAC-IN-4; Zabadinostat

IUPAC/Chemical Name

N-(2-Amino-phenyl)-4-[1-(1,3-dimethyl-1H-pyrazol-4-ylmethyl)-piperidin-4-yl]-benzamide

InChi Key

JHDZMASHNBKTPS-UHFFFAOYSA-N

InChi Code

InChI=1S/C24H29N5O/c1-17-21(15-28(2)27-17)16-29-13-11-19(12-14-29)18-7-9-20(10-8-18)24(30)26-23-6-4-3-5-22(23)25/h3-10,15,19H,11-14,16,25H2,1-2H3,(H,26,30)

SMILES Code

O=C(NC1=CC=CC=C1N)C2=CC=C(C3CCN(CC4=CN(C)N=C4C)CC3)C=C2

Appearance

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

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#C20R01B17

QC Data

View QC Data: Current Batch, Lot#C20R01B17

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

CXD101 is a potent, selective and orally active class I HDAC inhibitor with IC50s of 63 nM, 570 nM and 550 nM for HDAC1, HDAC2 and HDAC3, respectively.

In vitro activity:

Many of the MHC class I and class II genes within the AP signature were upregulated at the single gene level in SW620 cells treated with CXD101 (Fig. 1Fi). When the same set of AP signature genes was analysed in other cell lines, including the CRC HCT116 cells, breast cancer MCF7 cells and lung cancer A549 cells, CXD101 treatment caused a similar increase in gene expression (Fig. S2B–G). Genes within the NK signature were also measured where many, at the single gene level, exhibited increased expression in treated cells (Fig. 1Fii). These results highlight the ability of CXD101 to regulate immune-relevant gene expression. Reference: Mol Oncol. 2021 Mar 26. https://doi.org/10.1002/1878-0261.12953

In vivo activity:

To assess gene expression in the TME, the effect of CXD101 was evaluated in the syngeneic colon26 carcinoma model in tumours grown subcutaneously in Balb/c mice, with CXD101 given orally for two consecutive 5-day periods. RNA-seq was performed on polyA-enriched RNA purified from the tumours. Formalin-fixed paraffin-embedded samples were prepared in parallel to assess by immunohistochemistry (IHC) any change in the cellular content of the TME. CXD101 treatment caused a significant inhibition of tumour growth with minimal effect on body weight (Fig. 3A). The tumour RNA-seq data were aligned to the reference M. musculus genome (mm10) with STAR aligner where over 90% of the reads mapped to the mouse genome. DEGs (|log2 FC| >1 and FDR <1%) that were upregulated and downregulated were analzed and a heat map of the expression changes where many genes were upregulated with a smaller group downregulated upon CXD101 treatment was created (Fig. 3B). Similarly, PGSEA revealed a proportion of the DEGs in the tumour RNA-seq data associated with KEGG pathways with immune-related functions (Fig. 3B). The same two KEGG pathways namely ‘Antigen Processing and Presentation’ (AP) and ‘Natural Killer Cell-Mediated Cytotoxicity’ (NK) were found to be enriched in the CXD101 tumour expression data (Fig. 3C). In the GO term, enrichment analysis performed with PGSEA, MHC-associated genes and other immune-related terms were enriched upon CXD101 treatment (Fig. 3D). In a side-by-side comparison of the AP and NK signatures, a majority of genes within each pathway were upregulated upon CXD101 treatment (Fig. 3E,F). Reference: Mol Oncol. 2021 Mar 26. https://doi.org/10.1002/1878-0261.12953

	Solvent	mg/mL	mM
Solubility
	DMSO	31.0	76.82

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 403.53 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:

In vitro protocol:

1. Blaszczak W, Liu G, Zhu H, Barczak W, Shrestha A, Albayrak G, Zheng S, Kerr D, Samsonova A, La Thangue NB. Immune modulation underpins the anti-cancer activity of HDAC inhibitors. Mol Oncol. 2021 Mar 26. doi: 10.1002/1878-0261.12953. Epub ahead of print. PMID: 33773029.

In vivo protocol:

1: Liu J, Qian C, Zhu Y, Cai J, He Y, Li J, Wang T, Zhu H, Li Z, Li W, Hu L. Design, synthesis and evaluate of novel dual FGFR1 and HDAC inhibitors bearing an indazole scaffold. Bioorg Med Chem. 2017 Dec 29. pii: S0968-0896(17)32183-1. doi: 10.1016/j.bmc.2017.12.041. [Epub ahead of print] PubMed PMID: 29317150. 2: Yao R, Han D, Sun X, Xie Y, Wu Q, Fu C, Yao Y, Li H, Li Z, Xu K. Scriptaid inhibits cell survival, cell cycle and promotes apoptosis in multiple myeloma via epigenetic regulation of p21. Exp Hematol. 2018 Jan 2. pii: S0301-472X(17)30911-6. doi: 10.1016/j.exphem.2017.12.012. [Epub ahead of print] PubMed PMID: 29305109. 3: Lee HY, Nepali K, Huang FI, Chang CY, Lai MJ, Li YH, Huang HL, Yang CR, Liou JP. (N-Hydroxycarbonylbenylamino)quinolines as Selective Histone Deacetylase 6 Inhibitors Suppress Growth of Multiple Myeloma in vitro and in Vivo. J Med Chem. 2018 Jan 5. doi: 10.1021/acs.jmedchem.7b01404. [Epub ahead of print] PubMed PMID: 29304284. 4: Soukupova J, Bertran E, Peñuelas-Haro I, Urdiroz-Urricelqui U, Borgman M, Kohlhof H, Fabregat I. Resminostat induces changes in epithelial plasticity of hepatocellular carcinoma cells and sensitizes them to sorafenib-induced apoptosis. Oncotarget. 2017 Nov 30;8(66):110367-110379. doi: 10.18632/oncotarget.22775. eCollection 2017 Dec 15. PubMed PMID: 29299154; PubMed Central PMCID: PMC5746389. 5: Arrizabalaga O, Moreno-Cugnon L, Auzmendi-Iriarte J, Aldaz P, de Cáceres II, Garros-Regulez L, Moncho-Amor V, Torres-Bayona S, Pernía O, Pintado-Berninches L, Carrasco-Ramirez P, Cortes-Sempere M, Rosas R, Sanchez-Gomez P, Ruiz I, Caren H, Pollard S, Garcia I, Sacido AA, Lovell-Badge R, Belda-Iniesta C, Sampron N, Perona R, Matheu A. High expression of MKP1/DUSP1 counteracts glioma stem cell activity and mediates HDAC inhibitor response. Oncogenesis. 2017 Dec 14;6(12):401. doi: 10.1038/s41389-017-0003-9. PubMed PMID: 29284798. 6: Damaskos C, Tomos I, Garmpis N, Karakatsani A, Dimitroulis D, Garmpi A, Spartalis E, Kampolis CF, Tsagkari E, Loukeri AA, Margonis GA, Spartalis M, Andreatos N, Schizas D, Kokkineli S, Antoniou EA, Nonni A, Tsourouflis G, Markatos K, Kontzoglou K, Kostakis A, Tomos P. Histone Deacetylase Inhibitors as a Novel Targeted Therapy Against Non-small Cell Lung Cancer: Where Are We Now and What Should We Expect? Anticancer Res. 2018 Jan;38(1):37-43. Review. PubMed PMID: 29277754. 7: Harrison IF, Smith AD, Dexter DT. Pathological histone acetylation in Parkinson's disease: Neuroprotection and inhibition of microglial activation through SIRT 2 inhibition. Neurosci Lett. 2017 Dec 19;666:48-57. doi: 10.1016/j.neulet.2017.12.037. [Epub ahead of print] PubMed PMID: 29273397. 8: Xu J, Sun J, Wang P, Ma X, Li S. Pendant HDAC inhibitor SAHA derivatised polymer as a novel prodrug micellar carrier for anticancer drugs. J Drug Target. 2017 Dec 27:1-10. doi: 10.1080/1061186X.2017.1419355. [Epub ahead of print] PubMed PMID: 29251528. 9: Brookes RL, Crichton S, Wolfe CDA, Yi Q, Li L, Hankey GJ, Rothwell PM, Markus HS. Sodium Valproate, a Histone Deacetylase Inhibitor, Is Associated With Reduced Stroke Risk After Previous Ischemic Stroke or Transient Ischemic Attack. Stroke. 2018 Jan;49(1):54-61. doi: 10.1161/STROKEAHA.117.016674. Epub 2017 Dec 15. PubMed PMID: 29247141. 10: Li Q, Ding C, Meng T, Lu W, Liu W, Hao H, Cao L. Butyrate suppresses motility of colorectal cancer cells via deactivating Akt/ERK signaling in histone deacetylase dependent manner. J Pharmacol Sci. 2017 Dec;135(4):148-155. doi: 10.1016/j.jphs.2017.11.004. Epub 2017 Nov 24. PubMed PMID: 29233468. 11: Chidambaram A, Kavya SH, Chidambaram RK, Subbiah R, Jayaraj JM, Muthusamy K, Vilwanathan R. Design, synthesis and characterization of α, β-unsaturated carboxylic acid and its urea based derivatives that explores novel epigenetic modulators in human non-small cell lung cancer A549 cell line. J Cell Physiol. 2017 Dec 7. doi: 10.1002/jcp.26333. [Epub ahead of print] PubMed PMID: 29215703. 12: Takamura T, Horinaka M, Yasuda S, Toriyama S, Aono Y, Sowa Y, Miki T, Ukimura O, Sakai T. FGFR inhibitor BGJ398 and HDAC inhibitor OBP-801 synergistically inhibit cell growth and induce apoptosis in bladder cancer cells. Oncol Rep. 2018 Feb;39(2):627-632. doi: 10.3892/or.2017.6127. Epub 2017 Dec 1. PubMed PMID: 29207153. 13: Xie R, Li Y, Tang P, Yuan Q. Design, synthesis and biological evaluation of novel 2-aminobenzamides containing dithiocarbamate moiety as histone deacetylase inhibitors and potent antitumor agents. Eur J Med Chem. 2018 Jan 1;143:320-333. doi: 10.1016/j.ejmech.2017.08.041. Epub 2017 Aug 22. PubMed PMID: 29202397. 14: Ganai SA, Abdullah E, Rashid R, Altaf M. Combinatorial In Silico Strategy towards Identifying Potential Hotspots during Inhibition of Structurally Identical HDAC1 and HDAC2 Enzymes for Effective Chemotherapy against Neurological Disorders. Front Mol Neurosci. 2017 Nov 9;10:357. doi: 10.3389/fnmol.2017.00357. eCollection 2017. PubMed PMID: 29170627; PubMed Central PMCID: PMC5684606. 15: Liu TP, Hong YH, Yang PM. In silico and in vitro identification of inhibitory activities of sorafenib on histone deacetylases in hepatocellular carcinoma cells. Oncotarget. 2017 Sep 16;8(49):86168-86180. doi: 10.18632/oncotarget.21030. eCollection 2017 Oct 17. PubMed PMID: 29156785; PubMed Central PMCID: PMC5689675. 16: Bian X, Liang Z, Feng A, Salgado E, Shim H. HDAC inhibitor suppresses proliferation and invasion of breast cancer cells through regulation of miR-200c targeting CRKL. Biochem Pharmacol. 2018 Jan;147:30-37. doi: 10.1016/j.bcp.2017.11.008. Epub 2017 Dec 1. PubMed PMID: 29155146; PubMed Central PMCID: PMC5733635. 17: Soflaei SS, Momtazi AA, Majeed M, Derosa G, Maffioli P, Sahebkar A. Curcumin: a natural pan-HDAC inhibitor in cancer. Curr Pharm Des. 2017 Nov 14. doi: 10.2174/1381612823666171114165051. [Epub ahead of print] PubMed PMID: 29141538. 18: Booth L, Roberts JL, Poklepovic A, Kirkwood J, Dent P. HDAC inhibitors enhance the immunotherapy response of melanoma cells. Oncotarget. 2017 May 17;8(47):83155-83170. doi: 10.18632/oncotarget.17950. eCollection 2017 Oct 10. PubMed PMID: 29137331; PubMed Central PMCID: PMC5669957. 19: Tarasenko N, Chekroun-Setti H, Nudelman A, Rephaeli A. Comparison of the anticancer properties of a novel valproic acid prodrug to leading histone deacetylase inhibitors. J Cell Biochem. 2017 Nov 14. doi: 10.1002/jcb.26512. [Epub ahead of print] PubMed PMID: 29135083. 20: Poli G, Di Fabio R, Ferrante L, Summa V, Botta M. Largazole Analogues as Histone Deacetylase Inhibitors and Anticancer Agents: An Overview of Structure-Activity Relationships. ChemMedChem. 2017 Dec 7;12(23):1917-1926. doi: 10.1002/cmdc.201700563. Epub 2017 Nov 17. Review. PubMed PMID: 29117473.