Category: 122110-53-6

Batova, Ayse published the artcileThe histone deacetylase inhibitor AN-9 has selective toxicity to acute leukemia and drug-resistant primary leukemia and cancer cell lines, Formula: C10H18O4, the publication is Blood (2002), 100(9), 3319-3324, database is CAplus and MEDLINE.

The novel prodrug of butyric acid, pivaloyloxymethyl butyrate (AN-9), a histone deacetylase inhibitor, shows great promise as an effective and relatively nontoxic anticancer agent for solid malignancies. However, little is known about its effects on hematopoietic malignancies. In this study, the authors show that 21 primary samples of acute leukemia were sensitive to the antiproliferative effects of AN-9, with a 50% inhibitory concentration (IC₅₀) of 45.8 μM. In colony-forming assays, primary T-cell acute lymphoblastic leukemia (T-ALL) cells were 3-fold more sensitive to AN-9 than the normal hematopoietic progenitors, erythroid burst-forming units, and granulocyte/monocyte colony-forming units. AN-9 induced apoptosis in the T-ALL cell line CEM. A common problem with cancer is chemoresistance, which is often typical of relapsed cancers. Remarkably, a T-ALL sample at diagnosis and an acute myeloid leukemia sample at relapse that were resistant to doxorubicin in vitro were sensitive to AN-9, with an IC₅₀ of 50 μM for both samples. More strikingly, samples from 2 infants with t(4;11) ALL obtained at diagnosis and relapse each were the most sensitive to AN-9, with IC₅₀ values of 25 and 17 μM, resp. Furthermore, a doxorubicin-resistant clone of HL60, HL60/ADR, obtained by the transfection of the MDR-1 gene, was equally sensitive to AN-9 cytotoxicity as the parental cells. AN-9 induced the expression of p21 in an infant leukemia sample with 11q23 rearrangement, but not in T- or B-precursor ALL. Collectively, the authors’ results suggest that AN-9 is a selective agent for hematopoietic malignancies that can circumvent the mechanisms of chemoresistance limiting most conventional chemotherapy.

Blood 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, Formula: C10H18O4.

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

Nudelman, Abraham published the artcileNovel anticancer prodrugs of butyric acid. 2, Computed Properties of 122110-53-6, the publication is Journal of Medicinal Chemistry (1992), 35(4), 687-94, database is CAplus and MEDLINE.

The antitumor activity of novel prodrugs of butyric acid was examined The in vitro effect of the compounds on induction of cytodifferentiation and on inhibition of proliferation and clonogenicity showed that (pivaloyloxy)methyl butyrate (I) was the most active drug. Structure-activity relation study suggested that its activity stemmed from hydrolytically released butyric acid. In vivo, I displayed antitumor activity in B16F0 melanoma primary cancer model, manifested by a significant increase in the life span of the treated animals. Murine lung tumor burden, induced by injection of the highly metastatic melanoma cells (B16F10.9), was decrease byd I. It also displayed a significant therapeutic activity against spontaneous metastases which were induced by 3LL Lewis lung carcinoma cells. Moreover, I has the advantage of low toxicity, with an acute LD₅₀ = 1.36 g/kg). I is a potential antineoplastic agent.

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, Computed Properties of 122110-53-6.

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

Patnaik, Amita published the artcileA phase I study of pivaloyloxymethyl butyrate, a prodrug of the differentiating agent butyric acid, in patients with advanced solid malignancies, Safety of (Pivaloyloxy)methyl butyrate, the publication is Clinical Cancer Research (2002), 8(7), 2142-2148, database is CAplus and MEDLINE.

Pivaloyloxymethyl butyrate (AN-9), an acyloxyalkyl ester prodrug of butyric acid (BA), has demonstrated greater potency than BA at inducing malignant cell differentiation and tumor growth inhibition and has demonstrated more favorable toxicol., pharmacol., and pharmaceutical properties than BA in preclin. studies. The principal objective of this study was to determine the feasibility of administering AN-9 as a 6-h i.v. infusion daily for 5 days every 3 wk in patients with advanced solid malignancies. The study also sought to determine the principal toxicities and maximum tolerated dose of AN-9 on this intermittent schedule, as well as the effects of AN-9 on fetal Hb production, a parameter indicative of RBC differentiation. None of the 28 patients treated with 85 total courses of AN-9 at dosages ranging from 0.047 to 3.3 g/m²/day every 3 wk experienced dose limiting toxicity. Mild to moderate nausea, vomiting, hepatic transaminase elevation, hyperglycemia, fever, fatigue, anorexia, injection site reaction, diarrhea, and visual complaints were observed Dose escalation of AN-9 was limited by the maximum feasible volume of its intralipid formulation vehicle that could be administered safely on this schedule, resulting in a maximum deliverable dose of 3.3 g/m²/day. There was no consistent increase in fetal Hb with AN-9 treatment. A partial response was observed in a previously untreated patient with metastatic non-small cell lung cancer. Addnl. disease-directed clin. evaluations of AN-9 are necessary to establish the breadth of its antitumor activity and to assess its role as an effective differentiating agent.

Clinical 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, Safety of (Pivaloyloxy)methyl butyrate.

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

Gridelli, Cesare published the artcileThe potential role of histone deacetylase inhibitors in the treatment of non-small-cell lung cancer., Synthetic Route of 122110-53-6, the publication is Critical reviews in oncology/hematology (2008), 68(1), 29-36, database is MEDLINE.

Non-small-cell lung cancer (NSCLC) arises from a complex series of genetic and epigenetic changes leading to uncontrolled cell growth and metastases. The exponential growth in the level of research about the histone deacetylase (HDAC) enzymes, responsible for deacetylating core nucleosomal histones and other proteins, has been driven by the ability of HDAC inhibitors to modulate transcriptional activity. As a result, this therapeutic class is able to block angiogenesis and cell cycling, and promote apoptosis and differentiation. The mechanisms resulting in the antiproliferative biologic effects of these agents are not yet known. Clinical experience indicates these agents generally well tolerated, and active in several haematological and solid tumours. HDAC inhibitors, under clinical evaluation in the treatment of NSCLC patients, are pivanex, CI-994, vorinostat, and LBH589. Here, we discuss about the potential role of HDAC inhibitors focusing on their activity, tolerability, efficacy and future development, in the treatment of NSCLC.

Critical reviews in oncology/hematology 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

Parker, Belinda S. published the artcileFormation of mitoxantrone adducts in human tumor cells: potentiation by AN-9 and DNA methylation, Application of (Pivaloyloxy)methyl butyrate, the publication is Oncology Research (2004), 14(6), 279-290, database is CAplus and MEDLINE.

The ability of mitoxantrone to form DNA adducts was investigated in a series of human tumor cell lines consisting of human cervical cancer (HeLa), human breast cancer (MCF-7), and human neuroblastoma (IMR-32) cells. The mitoxantrone-resistant human promyelocytic leukemia cell line HL60/MX2 was also compared to the parental cell line HL60 in terms of adduct formation in cellular DNA, RNA, and protein. DNA adduct formation detected using [¹⁴C]mitoxantrone as a single agent occurred at very low levels but addition of the formaldehyde-releasing prodrug AN-9 (pivaloyloxymethyl butyrate) increased adduct formation considerably in all cell lines tested. Adduct formation increased when increasing ratios of AN-9 were used, and were observed at maximal levels when AN-9 addition was 4 h after the addition of mitoxantrone. However, low levels of adducts were observed when AN-9 addition was 16 h prior to mitoxantrone. The ability of [¹⁴C]mitoxantrone to form adducts with DNA, RNA, and protein was assessed in HL60 cells, and DNA was found to be the major substrate for adduct formation. RNA was also shown to be a good substrate while protein adduct levels were consistently very low. In mitoxantrone-resistant HL60/MX2 cells, DNA adduct levels were approx. fourfold lower. To establish the influence of DNA methylation on the ability of mitoxantrone to form adducts in cells, decitabine was used to reduce DNA methylation levels in cells prior to mitoxantrone treatment. This was clearly shown to influence adduct formation, with increasing decitabine levels leading to a decrease in the level of adducts observed in both IMR-32 and MCF-7 cell lines. Collectively, these results suggest that two major factors that influence the extent of mitoxantrone adduct formation in cells are the availability of formaldehyde and the extent of genomic DNA methylation.

Oncology 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

Entin-Meer, Michal published the artcileButyric acid prodrugs are histone deacetylase inhibitors that show antineoplastic activity and radiosensitizing capacity in the treatment of malignant gliomas, Name: (Pivaloyloxy)methyl butyrate, the publication is Molecular Cancer Therapeutics (2005), 4(12), 1952-1961, database is CAplus and MEDLINE.

Histone modification has emerged as a promising approach to cancer therapy. We explored the efficacy of a novel class of histone deacetylase inhibitors in the treatment of malignant gliomas. Treatment of glioma cell lines with two butyric acid derivatives, pivaloylomethyl butyrate (AN-9) and butyroyloxymethyl butyrate (AN-1), induced hyperacetylation, increased p21^Cip1 expression, inhibited proliferation, and enhanced apoptosis. Histone deacetylase inhibitor-induced apoptosis was mediated primarily by caspase-8. Treatment of cells with AN-1 or AN-9 for 24 h before exposure to γ-irradiation potentiated further caspase-8 activity and resultant apoptosis. Clonogenic survival curves revealed marked reductions in cell renewal capacity of U251 MG cells exposed to combinations of AN-1 and radiation. Preliminary in vivo experiments using human glioma cell lines grown as xenografts in mouse flanks suggest in vivo efficacy of AN-9. The data suggest that novel butyric acid prodrugs provide a promising treatment strategy for malignant gliomas as single agents and in combination with radiation therapy.

Molecular Cancer Therapeutics 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, Name: (Pivaloyloxy)methyl butyrate.

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

Cutts, Suzanne M. published the artcileMolecular basis for the synergistic interaction of adriamycin with the formaldehyde-releasing prodrug pivaloyloxymethyl butyrate (AN-9), Recommanded Product: (Pivaloyloxy)methyl butyrate, the publication is Cancer Research (2001), 61(22), 8194-8202, database is CAplus and MEDLINE.

The interaction of Adriamycin and pivaloyloxymethyl butyrate (AN-9) was investigated in IMR-32 neuroblastoma and MCF-7 breast adenocarcinoma cells. Adriamycin is a widely used anticancer drug, whereas AN-9 is an anticancer agent presently undergoing Phase II clin. trials. The anticancer activity of AN-9 has been attributed to its ability to act as a butyric acid prodrug, although it also releases formaldehyde and pivalic acid. Adriamycin and AN-9 in combination display synergy when exposed simultaneously to cells or when AN-9 treatment is up to 18 h after Adriamycin administration. However, the reverse order of addition results in antagonism. These interactions have been established using cell viability assays and classical isobologram anal. To understand the mol. basis of this synergy, the relative levels of Adriamycin-DNA adducts were determined using various treatment combinations. Levels of Adriamycin-DNA adducts were enhanced when treatment combinations known to be synergistic were used and were diminished using those treatments known to be antagonistic. The relative timing of the addition of Adriamycin and AN-9 was critical, with a 20-fold enhancement of Adriamycin-DNA adducts occurring when AN-9 was administered 2 h after the exposure of cells to Adriamycin. The enhanced levels of these adducts and the accompanying decreased cell viability were directly related to the esterase-dependent release of formaldehyde from AN-9, providing evidence for the formaldehyde-mediated activation of Adriamycin.

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, Recommanded Product: (Pivaloyloxy)methyl butyrate.

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

Aviram, Adina published the artcileEffect of the cytostatic butyric acid pro-drug, pivaloyloxymethyl butyrate, on the tumorigenicity of cancer cells, Recommanded Product: (Pivaloyloxy)methyl butyrate, the publication is Journal of Cancer Research and Clinical Oncology (1997), 123(5), 267-271, database is CAplus and MEDLINE.

Pivaloyloxymethyl butyrate (AN-9) was demonstrated to be a cytostatic but not cytotoxic agent in a myelomonocytic cell line (WEHI). The expression of the early regulatory genes, c-myc and c-jun were changed. Although these events occurred already after 1 h of exposure to AN-9, the tumorigenicity of these reduced only after 4 h of exposure. Tumorigenicity of the highly metastatic subclone of Lewis lung carcinoma was almost diminished after 1h of exposure. In both cell types a 10-fold higher concentration of BA did not affect the tumorigenicity of the cells as did AN-9.

Journal of Cancer Research and Clinical Oncology 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, Recommanded Product: (Pivaloyloxy)methyl butyrate.

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

Kasukabe, T. published the artcileAn anticancer derivative of butyric acid (pivalyloxymethyl butyrate) and daunorubicin cooperatively prolong survival of mice inoculated with monocytic leukemia cells, Synthetic Route of 122110-53-6, the publication is British Journal of Cancer (1997), 75(6), 850-854, database is CAplus and MEDLINE.

Pivalyloxymethyl butyrate (AN-9) inhibited the proliferation of and induced apoptosis in mouse monocytic leukemia Mm-A cells; Na butyrate, but not AN-9, induced differentiation of the cells. AN-9 and various DNA-specific antineoplastic agents synergistically inhibited the growth of Mm-A cells, and simultaneous treatment was required to evoke the maximum growth-inhibitory effect. On the other hand, there was no synergy between butyrate and these drugs, or between AN-9 and several antimetabolic agents, in inhibiting the growth of the cells, suggesting that the synergistic effect is specific to AN-9 and DNA-reacting agents. AN-9, given alone, dose-dependently prolonged the survival of mice inoculated with Mm-A cells. Moreover, administration of AN-9 plus daunorubicin (DNR) further prolonged survival.

British Journal of Cancer 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

Rephaeli, Ada published the artcileDerivatives of butyric acid as potential anti-neoplastic agents, COA of Formula: C10H18O4, the publication is International Journal of Cancer (1991), 49(1), 66-72, database is CAplus and MEDLINE.

A novel derivative of butyric acid, pivalyloxymethyl butyrate (AN-9) was shown, in vitro, to: (a) induce cytodifferentiation and inhibit the proliferation of leukemic cells; (b) inhibit the growth and formation of Lewis lung carcinoma colonies in semi-solid agar. AN-9 affect cells at about 10-fold lower concentration and at a faster rate than does butyric acid. The pivalyloxymethyl esters of propionic, isobutyric and valeric acids do not elicit effects similar to those of AN-9, while the isobutyryloxymethyl butyrate does, which strongly suggests that the activity of AN-9 stems from intracellular metabolic degradation of the pro-drug to butyric acid. In vivo, AN-9, increased the survival of mice in Lewis lung carcinoma primary cancer model and significantly decreased the number of lung lesions of the animals inoculated with highly metastatic cells, but did not affect their life span. Acute LD₅₀ studies showed that AN-9 possesses low toxicity. AN-9 is a potential antineoplastic agent as well as a tool for investigation of the differentiation induction mechanism.

International Journal of Cancer 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