Category: 122110-53-6

Nudelman, Abraham published the artcileProdrugs of butyric acid. Novel derivatives possessing increased aqueous solubility and potential for treating cancer and blood diseases, HPLC of Formula: 122110-53-6, the publication is European Journal of Medicinal Chemistry (2001), 36(1), 63-74, database is CAplus and MEDLINE.

The synthesis and biol. activities of acidic, basic and neutral types of butyric acid (BA) prodrugs possessing increased aqueous solubility are described. The compounds are butyroyloxyalkyl derivatives of carboxylic acids, which possess functionalities suitable for aqueous solubilization. The anticancer activity of the prodrugs in vitro was evaluated by examining their effect on the growth of human colon, breast and pancreatic carcinoma cell lines, and their solubility in aqueous media was determined The most promising compounds, with respect to activity and solubility, were the butyroyloxymethyl esters of glutaric and nicotinic acids and phosphoric acid as its di-Et ester, which displayed IC₅₀ values of 100 μM or lower. These prodrugs are expected to release formaldehyde upon metabolic hydrolysis. The corresponding butyroyloxymethyl esters that release acetaldehyde upon metabolism were significantly less potent. A similar correlation was observed for growth inhibition of the human prostate carcinoma cell lines PC-3 and LnCap and for induction of differentiation and apoptosis in the human myeloid leukemia cell line HL-60. The higher biol. activity of the formaldehyde-releasing prodrugs I and II was further confirmed when induction of Hb synthesis in the human erythroleukemic cell line K562 was measured. Moreover, a therapeutic index (IC₅₀/ED₅₀) of 5 was observed The acute i.p. toxicity LD₅₀ in mice for I, III, II and IV was similar and in the range of 400-600 mg kg^-1. The results obtained support the potential use of the butyric acid prodrugs for the treatment of neoplastic diseases and β-globin disorders.

European Journal of Medicinal Chemistry published new progress about 122110-53-6. 122110-53-6 belongs to esters-buliding-blocks, auxiliary class Aliphatic hydrocarbon chain,Ester,Inhibitor, name is (Pivaloyloxy)methyl butyrate, and the molecular formula is C10H18O4, HPLC of Formula: 122110-53-6.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Mansour, Oula C. published the artcileNew Anthracenedione Derivatives with Improved Biological Activity by Virtue of Stable Drug-DNA Adduct Formation, Product Details of C10H18O4, the publication is Journal of Medicinal Chemistry (2010), 53(19), 6851-6866, database is CAplus and MEDLINE.

Mitoxantrone is an anticancer agent that acts as a topoisomerase II poison, however, it can also be activated by formaldehyde to form DNA adducts. Pixantrone, a 2-aza-anthracenedione with terminal primary amino groups in its side chains, forms formaldehyde-mediated adducts with DNA more efficiently than mitoxantrone. Mol. modeling studies indicated that extension of the “linker” region of anthracenedione side arms would allow the terminal primary amino greater flexibility and thus access to the guanine residues on the opposite DNA strand. New derivatives based on the pixantrone and mitoxantrone backbones were synthesized, and these incorporated primary amino groups as well as extended side chains. The stability of DNA adducts increased with increasing side chain length of the derivatives A mitoxantrone derivative bearing extended side chains (I) formed the most stable adducts with ∼100-fold enhanced stability compared to mitoxantrone. This finding is of great interest because long-lived drug-DNA adducts are expected to perturb DNA-dependent functions at all stages of the cell cycle.

Journal of Medicinal Chemistry published new progress about 122110-53-6. 122110-53-6 belongs to esters-buliding-blocks, auxiliary class Aliphatic hydrocarbon chain,Ester,Inhibitor, name is (Pivaloyloxy)methyl butyrate, and the molecular formula is C10H18O4, Product Details of C10H18O4.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Rephaeli, Ada published the artcileThe selectivity and anti-metastatic activity of oral bioavailable butyric acid prodrugs, COA of Formula: C10H18O4, the publication is Investigational New Drugs (2006), 24(5), 383-392, database is CAplus and MEDLINE.

Acyloxyalkyl ester prodrugs of histone deacetylase inhibitors, a family of anti-cancer agents, are metabolized intracellularly to acids and aldehyde(s). The purpose of this study was to assess the in vitro and in vivo anticancer activity, selectivity and oral bioavailability of these prodrugs. The prodrugs exhibited a hierarchal potency of AN-193 ≥ AN-7 > AN-1 and AN-9 ≫ AN-10 against murine lung carcinoma (3LLD122) and human breast carcinoma (MCF-7) cell lines. AN-9, and to even greater extent AN-7, displayed preferential cytotoxicity against leukemic and glioblastoma cells compared to their normal cellular counterparts-normal mononuclear and astrocytes cells, resp. In vivo, anti-metastatic activity was evaluated in a metastatic model of lung cancer in which Lewis lung carcinoma (3LLD122) cells are injected i.v. into C57/BL mice and produce lung nodules. The prodrugs administered orally demonstrated a significant inhibition of lung-lesion formation and their hierarchal potency concurred with that observed in vitro, with the exception of AN-193 that was the least active compound Escalating doses of AN-7 (5-100 mg/kg), administered by oral or i.p. routes and displayed equivalent anti-metastatic activities, confirmed the good oral bioavailability of AN-7. Consistent with these findings, a time course study of histone acetylation in s.c. implanted 3LL122 tumors showed 2-4 fold increases in histone acetylation within 0.5 h of i.v., i.p., or oral administration of AN-7 (100 mg/kg). Relative contributions of the prodrug metabolites to the anti-neoplastic activity and the best candidate for clin. studies are discussed.

Investigational New Drugs published new progress about 122110-53-6. 122110-53-6 belongs to esters-buliding-blocks, auxiliary class Aliphatic hydrocarbon chain,Ester,Inhibitor, name is (Pivaloyloxy)methyl butyrate, and the molecular formula is C10H18O4, COA of Formula: C10H18O4.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Parker, Belinda S. published the artcileMitoxantrone mediates demethylation and reexpression of cyclin D2, estrogen receptor and 14.3.3σ in breast cancer cells, Quality Control of 122110-53-6, the publication is Cancer Biology & Therapy (2003), 2(3), 259-263, database is CAplus and MEDLINE.

In addition to its action as a topoisomerase II poison, mitoxantrone is activated by formaldehyde to bind DNA, forming DNA-adducts specifically at 5’CpG and CpA sequences, with an enhancement of adducts at methylated CpG sites. The butyric acid prodrug, AN-9 (pivaloyloxymethyl butyrate), releases formaldehyde upon cellular hydrolysis and our previous studies have shown that mitoxantrone acts synergistically with AN-9 in cytotoxicity assays. In this paper, we investigated the impact of methylation levels in the cell on mitoxantrone-induced cytotoxicity using the colon cancer cell line HCT116 and its derived DNA methyltransferase (DNMT) 1 and DNMT 3a knockout (DKO8) cell line. We found that decreased methylation levels in the DNMT-null cells led to at least a 2-fold reduction in mitoxantrone-induced cytotoxicity. Next, we studied the impact of mitoxantrone alone, and in combination with AN-9, on hypermethylated genes and their mRNA expression in breast cancer cells. Using methylation-specific PCR and RT-PCR, we found that mitoxantrone treatment of breast cancer cell lines resulted in demethylation of the 14.3.3σ, cyclin D2 and ERα genes, followed by re-expression of their mRNA. The effect of mitoxantrone on re-expression of key genes involved in cell cycle regulation, and ensuing death of the cells may be an addnl., previously undiscovered mechanism of action of mitoxantrone.

Cancer Biology & Therapy published new progress about 122110-53-6. 122110-53-6 belongs to esters-buliding-blocks, auxiliary class Aliphatic hydrocarbon chain,Ester,Inhibitor, name is (Pivaloyloxy)methyl butyrate, and the molecular formula is C10H18O4, Quality Control of 122110-53-6.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Dokmanovic, Milos published the artcileHistone Deacetylase Inhibitors: Overview and Perspectives, Product Details of C10H18O4, the publication is Molecular Cancer Research (2007), 5(10), 981-989, database is CAplus and MEDLINE.

A review. Histone deacetylase inhibitors (HDACi) comprise structurally diverse compounds that are a group of targeted anticancer agents. The first of these new HDACi, vorinostat (suberoylanilide hydroxamic acid), has received Food and Drug Administration approval for treating patients with cutaneous T-cell lymphoma. This review focuses on the activities of the 11 zinc-containing HDACs, their histone and nonhistone protein substrates, and the different pathways by which HDACi induce transformed cell death. A hypothesis is presented to explain the relative resistance of normal cells to HDACi-induced cell death.

Molecular Cancer Research published new progress about 122110-53-6. 122110-53-6 belongs to esters-buliding-blocks, auxiliary class Aliphatic hydrocarbon chain,Ester,Inhibitor, name is (Pivaloyloxy)methyl butyrate, and the molecular formula is C10H18O4, Product Details of C10H18O4.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Nudelman, Abraham published the artcileThe Role of Intracellularly Released Formaldehyde and Butyric Acid in the Anticancer Activity of Acyloxyalkyl Esters, SDS of cas: 122110-53-6, the publication is Journal of Medicinal Chemistry (2005), 48(4), 1042-1054, database is CAplus and MEDLINE.

Previous studies described a family of anticancer histone deacetylase inhibitor prodrugs of formula Me(CH₂)₂COOCH(R)OR¹, which upon intracellular hydrolysis release acids and aldehydes. This study examines the mechanisms by which the prodrugs affect tumor cells and the contribution of the released aldehyde (formaldehyde or acetaldehyde) and acids to their anticancer activity. Type I prodrugs release 2 equiv of a carboxylic acid and 1 equiv of an aldehyde, and of Type II release 2 equiv of acids and 2 equiv of an aldehyde. SAR studied inhibition of proliferation, induction of differentiation and apoptosis, histone acetylation, and gene expression. Formaldehyde, measured intracellularly, was the dominant factor affecting proliferation and cell death. Among the released acids, butyric acid elicited the greatest antiproliferative activity, but the nature of the acid had minor impact on proliferation. In HL-60 cells, formaldehyde-releasing prodrugs significantly increased apoptosis. The prodrugs affected to a similar extent the wild-type HL-60 and MES-SA cell lines and their multidrug-resistant HL-60/MX2 and MES-Dx5 subclones. In a cell-free histone deacetylase (HDAC) inhibition-assay only butyric acid inhibited HDAC activity. The butyric acid and formaldehyde induced cell differentiation and increased p53 and p21 levels, suggesting that both affect cancer cells, the acid by inhibiting HDAC and the aldehyde by an as yet unknown mechanism.

Journal of Medicinal Chemistry published new progress about 122110-53-6. 122110-53-6 belongs to esters-buliding-blocks, auxiliary class Aliphatic hydrocarbon chain,Ester,Inhibitor, name is (Pivaloyloxy)methyl butyrate, and the molecular formula is C10H18O4, SDS of cas: 122110-53-6.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Niitsu, Nozomi published the artcileAnticancer derivative of butyric acid (pivalyloxymethyl butyrate) specifically potentiates the cytotoxicity of doxorubicin and daunorubicin through the suppression of microsomal glycosidic activity, COA of Formula: C10H18O4, the publication is Molecular Pharmacology (2000), 58(1), 27-36, database is CAplus and MEDLINE.

Pivalyloxymethyl butyrate (AN9) is an anticancer derivative of butyric acid. In this study, doxorubicin (DXR) and AN9 synergistically inhibited the growth of lymphoma and lung carcinoma cells, whereas there was no synergy between AN9 and antimetabolites. AN9 did not affect the intracellular uptake of DXR. Among anthracyclines and their derivatives, the synergistic effect was prominent in compounds with a daunosamine moiety, suggesting that AN9 may affect the catabolism of these compounds The degradation of DXR in the extract from AN9-treated cells was much less than that in extract from untreated cells. AN9 did not directly inhibit the enzyme activity but rather suppressed expression of the enzyme. With respect to the expression of drug resistance-related genes, there was no significant difference between untreated and AN9-treated cells. However, AN9 significantly down-regulated the levels NADPH-cytochrome P 450 reductase and DT-diaphorase mRNA in the presence of DXR but not the level of xanthine oxidase mRNA. The enhancement of the sensitivity to anthracyclines was closely associated with the suppression of the mRNA expression.

Molecular Pharmacology published new progress about 122110-53-6. 122110-53-6 belongs to esters-buliding-blocks, auxiliary class Aliphatic hydrocarbon chain,Ester,Inhibitor, name is (Pivaloyloxy)methyl butyrate, and the molecular formula is C10H18O4, COA of Formula: C10H18O4.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Honma, Yoshio published the artcileDifferentiation therapy for monocytic leukemia using fatty acid derivatives, Application of (Pivaloyloxy)methyl butyrate, the publication is Recent Research Developments in Lipids Research (1997), 189-198, database is CAplus.

Myeloid leukemia cells can be induced to differentiate terminally into non-dividing mature cells by various compounds, including short chain fatty acids. Many monocytoid leukemia cell lines are relatively sensitive to butyrate and its analogs with regard to the induction of differentiation and inhibition of proliferation of the cells. To develop a novel therapy for monocytic leukemia, we studied the basic issues of differentiation therapy using fatty acid derivatives

Recent Research Developments in Lipids Research published new progress about 122110-53-6. 122110-53-6 belongs to esters-buliding-blocks, auxiliary class Aliphatic hydrocarbon chain,Ester,Inhibitor, name is (Pivaloyloxy)methyl butyrate, and the molecular formula is C10H18O4, Application of (Pivaloyloxy)methyl butyrate.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Niitsu, N. published the artcileDownregulation of MLL-CBP fusion gene expression is associated with differentiation of SN-1 cells with t(11;16)(q23;p13), Category: esters-buliding-blocks, the publication is Oncogene (2001), 20(3), 375-384, database is CAplus and MEDLINE.

The translocation t(11;16)(q23;p13) has only been documented in patients with acute leukemia or myelodysplasia secondary to therapy with drugs targeting DNA topoisomerase II. The authors have established a myeloid cell line (SN-1) with the MLL-CBP fusion gene from an acute leukemia patient with t(11;16)(q23;p13). Although SN-1 cells were not induced to differentiate by all-trans retinoic acid (ATRA) and 1α,25-dihydroxyvitamin D₃ (VD3), retinoid X receptor (RXR) agonists, such as 9-cis retinoic acid and Ro48-2250, effectively induced differentiation of the cells. Downregulation of the expression of the MLL-CBP fusion gene occurred during the differentiation of SN-1 cells. When SN-1 cells were treated with MLL-CBP antisense oligonucleotide, the cells were induced to differentiate by ATRA or VD3, suggesting that the MLL-CBP fusion gene dominant-neg. suppresses ATRA- or VD3-induced differentiation. Moreover, suboptimal concentrations of sodium butyrate, a histone deacetylase inhibitor, had a cooperative effect with ATRA or VD3 in inducing the differentiation of SN-1 cells. The downregulation of the expression of MLL-CBP mRNA was accompanied by the induction of differentiation. These findings suggest that RXR agonists or a clin. applicable combination of ATRA and butyrate derivatives might be useful for differentiation therapy in leukemia patients with the MLL-CBP fusion gene.

Oncogene published new progress about 122110-53-6. 122110-53-6 belongs to esters-buliding-blocks, auxiliary class Aliphatic hydrocarbon chain,Ester,Inhibitor, name is (Pivaloyloxy)methyl butyrate, and the molecular formula is C10H18O4, Category: esters-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Pontiki, Eleni published the artcileHistone deacetylase inhibitors (HDACIs). Structure-activity relationships: history and new QSAR perspectives, Synthetic Route of 122110-53-6, the publication is Medicinal Research Reviews (2012), 32(1), 1-165, database is CAplus and MEDLINE.

A review. Histone deacetylase (HDAC) inhibition is a recent, clin. validated therapeutic strategy for cancer treatment. HDAC inhibitors (HDACIs) block angiogenesis, arrest cell growth, and lead to differentiation and apoptosis in tumor cells. In this article, a survey of published quant. structure-activity relationships (QSARs) studies are presented and discussed in the hope of identifying the structural determinants for anticancer activity. Secondly a two-dimensional QSAR study was carried out on biol. results derived from various types of HDACIs and from different assays using the C-QSAR program of Biobyte. The QSAR anal. presented here is an attempt to organize the knowledge on the HDACIs with the purpose of designing new chem. entities with enhanced inhibitory potencies and to study the mechanism of action of the compounds This study revealed that lipophilicity is one of the most important determinants of activity. Addnl., steric factors such as the overall molar refractivity (CMR), molar volume (MgVol), the substituent’s molar refractivity (MR) (linear or parabola), or the sterimol parameters B₁ and L are important. Electronic parameters indicated as σ_p, are found to be present only in one case. © 2010 Wiley Periodicals, Inc. Med Res Rev 32:1-165, 2012.

Medicinal Research Reviews published new progress about 122110-53-6. 122110-53-6 belongs to esters-buliding-blocks, auxiliary class Aliphatic hydrocarbon chain,Ester,Inhibitor, name is (Pivaloyloxy)methyl butyrate, and the molecular formula is C10H18O4, Synthetic Route of 122110-53-6.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics