Category: 122110-53-6

Entin-Meer, Michal published the artcileIn vivo efficacy of a novel histone deacetylase inhibitor in combination with radiation for the treatment of gliomas, Safety of (Pivaloyloxy)methyl butyrate, the publication is Neuro-Oncology (Durham, NC, United States) (2007), 9(2), 82-88, database is CAplus and MEDLINE.

Histone modification has emerged as a promising approach to cancer therapy. We explored the in vivo efficacy of a butyric acid derivative, pivaloyloxymethyl butyrate (AN-9), for the treatment of gliomas. Relative to control and single-modality treatments, the combination of AN-9 and radiation significantly inhibited tumor growth and prolonged time to failure in mice bearing glioma xenografts. The enhanced response to radiation was accompanied by inhibition of cellular proliferation and by increased phosphorylation of H2AX, implicating DNA double-strand breaks in the antineoplastic effects of AN-9 and radiation. The data suggest that AN-9 in combination with radiation may be an effective therapy for malignant gliomas.

Neuro-Oncology (Durham, NC, United States) 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

Zimra, Yael published the artcileButyric acid and pivaloyloxymethyl butyrate, AN-9, a novel butyric acid derivative, induce apoptosis in HL-60 cells, Formula: C10H18O4, the publication is Journal of Cancer Research and Clinical Oncology (1997), 123(3), 152-160, database is CAplus and MEDLINE.

It is shown that AN-9 and butyrate induce cell death by apoptosis. Exposure of HL-60 cells to butyrate and AN-9 decreased cell numbers and induced cell differentiation and the appearance of typical apoptotic features. Induction of apoptosis and/or differentiation was dependent on the concentration and the time of exposure to the drugs. The advantage of An-9 over butyrate was further confirmed. AN-9-induced apoptosis occurred after a shorter exposure and at lower drug concentrations than that induced by butyrate. Apoptosis by AN-9 was accompanied by reduction in Bcl-2 expression. Preincubation with antioxidants did not protect HL-60 cells from apoptosis induced by 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 C19H36BNO2Si, Formula: C10H18O4.

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

Siu, Lillian L. published the artcileActivity of pivaloyloxymethyl butyrate, a novel anticancer agent, on primary human tumor colony-forming units, Recommanded Product: (Pivaloyloxy)methyl butyrate, the publication is Investigational New Drugs (1998), 16(2), 113-119, database is CAplus and MEDLINE.

The anti-proliferative effects of pivaloyloxymethyl butyrate (AN-9), a butyric acid (BA) derivative with potent tumor-differentiating properties both in vitro and in vivo, was evaluated against colorectal, breast, lung, ovarian, renal cell, bladder, and other types of tumor colony-forming units in a human tumor cloning assay. A total of 76 evaluable specimens were exposed to AN-9 continuously, 48 of these were also exposed to BA continuously for direct comparison of the two agents, and 20 specimens were exposed to AN-9 for two hours. An in vitro inhibitory response was defined as a â‰?50% decrease in tumor colony formation in treated cells compared to untreated controls. Superior anti-tumor activity was observed with the continuous exposure to AN-9 (39% in vitro response at 100 μM and 70% at 200 μM) than with the two-hour exposure (20% at 100 μM and 25% at 200 μM). At a continuous concentration of 200 μM, AN-9 demonstrated greater tumor-specific activity than BA against melanoma (100% vs. 67%), ovarian (67% vs. 40%), breast (63% vs. 0%), non-small cell lung (60% vs. 10%), and colorectal tumor colony-forming units (62% vs. 20%). AN-9 is a novel differentiating agent with activity against colony-forming units derived from a variety of primary human tumors, including those that are considered relatively chemoresistant, and may thus provide a therapeutic alternative or addition to standard cytotoxic agents, if appropriate drug concentrations can be achieved in patients.

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 C17H14F3N3O2S, Recommanded Product: (Pivaloyloxy)methyl butyrate.

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

Reid, Tony published the artcilePhase II trial of the histone deacetylase inhibitor pivaloyloxymethyl butyrate (Pivanex, AN-9) in advanced non-small cell lung cancer., Computed Properties of 122110-53-6, the publication is Lung cancer (Amsterdam, Netherlands) (2004), 45(3), 381-6, database is MEDLINE.

This multicenter phase II trial evaluated the therapeutic activity and safety profile of pivaloyloxymethyl butyrate (Pivanex, AN-9) as a single agent in refractory non-small cell lung cancer (NSCLC). Pivanex (2.34 g/m2 per day) was administered as a 6-h continuous intravenous infusion, daily for 3 days, and repeated every 21 days until disease progression. Forty-seven patients were treated. More than 90% of patients had received both a platinum compound and a taxane and 32% had received three or more prior chemotherapy regimens. The most common toxicities were transient grade 1-2 fatigue (34%), nausea (17%), and dysgeusia (11%). Three patients had partial responses (6.4 and 95%; CI 1.4-18.7%) and 14 patients had stable disease for > or =12 weeks (30%). Median survival for all patients was 6.2 months with 1-year survival of 26%. For patients who received fewer than three prior chemotherapy regimens, median survival was 7.8 months and 1-year survival was 31%. Pivanex is well tolerated and appears to be active as a single agent in patients with advanced NSCLC refractory to previous chemotherapy. Based on its therapeutic activity and favorable safety profile, further studies of Pivanex in NSCLC, particularly in combination with current chemotherapeutic agents, are warranted.

Lung cancer (Amsterdam, Netherlands) 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

Forrest, Robert A. published the artcileThe hydroxyl epimer of doxorubicin controls the rate of formation of cytotoxic anthracycline-DNA adducts, Related Products of esters-buliding-blocks, the publication is Cancer Chemotherapy and Pharmacology (2013), 71(3), 809-816, database is CAplus and MEDLINE.

Epirubicin was developed as a semi-synthetic anthracycline derivative to circumvent the cardiotoxic limitations associated with the use of doxorubicin in the clinic. Anthracycline compounds have been demonstrated to form covalent drug-DNA adducts utilizing endogenous and exogenous sources of formaldehyde; however, previous investigations of the formation of epirubicin-DNA adducts provide conflicting evidence for adduct formation. This work provides evidence that epirubicin acts to form drug-DNA adducts at physiol. relevant concentrations and demonstrates that the rate of formation of epirubicin-DNA adducts is slower than that observed for other anthracycline compounds, explaining why they are only detectable under defined exptl. conditions. Formation of covalent epirubicin-DNA adducts improves the apoptotic profile of epirubicin and provides opportunities to overcome drug resistance and cardiotoxic limitations.

Cancer Chemotherapy and 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, Related Products of esters-buliding-blocks.

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

Cutts, Suzanne M. published the artcileSequence specificity of adriamycin-DNA adducts in human tumor cells, COA of Formula: C10H18O4, the publication is Molecular Cancer Therapeutics (2003), 2(7), 661-670, database is CAplus and MEDLINE.

The anticancer anthracycline compound Adriamycin is a known topoisomerase II inhibitor but is also capable of exerting other cellular consequences. After intercalation, Adriamycin can form covalent adducts with DNA, and the magnitude of these adducts appears to be limited by the cellular availability of formaldehyde. Adducts produced by Adriamycin in the presence of formaldehyde have been well characterized in cell-free systems but not in cells. In this study, we show that when Adriamycin is used in conjunction with the formaldehyde-releasing prodrug AN-9 in IMR-32 tumor cells, this allows the formation of sufficiently high levels of adducts in genomic DNA to enable detection of their DNA sequence specificity for the first time. The 340-bp α-satellite EcoRI repeat sequence was isolated from drug-treated cells and digested with λ-exonuclease to determine adduct sites at which exonuclease digestion was blocked. The Adriamycin adducts were formed predominantly at 5′-GC and GG sequences and unstable with respect to elevated temperatures and extended times at 37°. The use of three anthracycline derivatives lacking a 3’amino group demonstrated that this amino portion is critical for the formation of anthracycline adducts in cells. The structure of these drug-DNA adducts can therefore be considered to be identical to the Adriamycin adducts, which have been characterized rigorously in cell-free systems by x-ray crystallog., two-dimensional NMR, and mass spectrometry.

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, COA of Formula: C10H18O4.

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

Cutts, Suzanne M. published the artcileActivation of clinically used anthracyclines by the formaldehyde-releasing prodrug pivaloyloxymethyl butyrate, Category: esters-buliding-blocks, the publication is Molecular Cancer Therapeutics (2007), 6(4), 1450-1459, database is CAplus and MEDLINE.

The anthracycline group of compounds is extensively used in current cancer chemotherapy regimens and is classified as topoisomerase II inhibitor. However, previous work has shown that doxorubicin can be activated to form DNA adducts in the presence of formaldehyde-releasing prodrugs and that this leads to apoptosis independently of topoisomerase II-mediated damage. To determine which anthracyclines would be useful in combination with formaldehyde-releasing prodrugs, a series of clin. relevant anthracyclines (doxorubicin, daunorubicin, idarubicin, and epirubicin) were examined for their capacity to form DNA adducts in MCF7 and MCF7/Dx (P-glycoprotein overexpressing) cells in the presence of the formaldehyde-releasing drug pivaloyloxymethyl butyrate (AN-9). All anthracyclines, with the exception of epirubicin, efficiently yielded adducts in both sensitive and resistant cell lines, and levels of adducts were similar in mitochondrial and nuclear genomes. Idarubicin was the most active compound in both sensitive and resistant cell lines, whereas adducts formed by doxorubicin and daunorubicin were consistently lower in the resistant compared with sensitive cells. The adducts formed by doxorubicin, daunorubicin, and idarubicin showed the same DNA sequence specificity in sensitive and resistant cells as assessed by λ-exonuclease-based sequencing of α-satellite DNA extracted from drug-treated cells. Growth inhibition assays were used to show that doxorubicin, daunorubicin, and idarubicin were all synergistic in combination with AN-9, whereas the combination of epirubicin with AN-9 was additive. Although apoptosis assays indicated a greater than additive effect for epirubicin/AN-9 combinations, this effect was much more pronounced for doxorubicin/AN-9 combinations. [Mol Cancer Ther 2007;6(4):1450-9].

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, Category: esters-buliding-blocks.

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

Koch, Bjoern E. V. published the artcileA quantitative in vivo assay for craniofacial developmental toxicity of histone deacetylases, Quality Control of 122110-53-6, the publication is Toxicology Letters (2021), 20-25, database is CAplus and MEDLINE.

Many bony features of the face develop from endochondral ossification of preexisting collagen-rich cartilage structures. The proper development of these cartilage structures is essential to the morphol. formation of the face. The developmental programs governing the formation of the pre-bone facial cartilages are sensitive to chem. compounds that disturb histone acetylation patterns and chromatin structure. We have taken advantage of this fact to develop a quant. morphol. assay of craniofacial developmental toxicity based on the distortion and deterioration of facial cartilage structures in zebrafish larvae upon exposure to increasing concentrations of several well-described histone deacetylase inhibitors. In this assay, we measure the angle formed by the developing ceratohyal bone as a precise, sensitive and quant. proxy for the overall developmental status of facial cartilages. Using the well-established developmental toxicant and histone deacetylase-inhibiting compound valproic acid along with 12 structurally related compounds, we demonstrate the applicability of the ceratohyal angle assay to investigate structure-activity relationships.

Toxicology Letters 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

Rabizadeh, E published the artcileEsterase inhibitors diminish the modulation of gene expression by butyric acid derivative, pivaloyloxymethyl butyrate (AN-9)., Safety of (Pivaloyloxy)methyl butyrate, the publication is Israel journal of medical sciences (1996), 32(12), 1186-91, database is MEDLINE.

Pivaloyloxymethyl butyrate (AN-9) belongs to the family of acyloxyalkyl ester prodrugs of carboxylic acids which undergo intracellular hydrolysis to yield butyric acid (BA). We have previously shown that AN-9 and BA reduce the level of c-myc and enhance c-jun transcripts in HL-60 cells, and that the differentiation of these cells, induced by AN-9, is dependent on the presence of intracellular esterases. In this study we show that esterase inhibitors abolish the changes induced by AN-9 on c-myc and c-jun expression. In contrast, esterase inhibitors do not change the effects of BA on c-myc or c-jun. Interestingly, these inhibitors affect the modulation induced by both AN-9 and BA on the retinoblastoma tumor suppressor gene. These data suggest that AN-9 is indeed a prodrug of BA and that prior intracellular hydrolysis by esterases is material for AN-9 activity.

Israel journal of medical sciences 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

Rabizadeh, Ester published the artcileRapid alteration of c-myc and c-jun expression in leukemic cells induced to differentiate by a butyric acid prodrug, Product Details of C10H18O4, the publication is FEBS Letters (1993), 328(3), 225-9, database is CAplus and MEDLINE.

The novel prodrug of butyric acid (BA), pivaloyloxymethyl butyrate, has been shown, in vitro, to induce differentiation and inhibit leukemic cell proliferation. The prodrug affects the cells in vitro at lower concentration and at least 100 times faster than does BA. The authors have compared the ability of BA with that of its prodrug AN-9 to modulate the expression of the early regulating genes, c-myc and c-jun, in HL-60 cells. Exposure of HL-60 cells to the prodrug resulted in a decrease of c-myc and an increase of c-jun expression. The prodrug elicited this effect at lower concentrations and at least 100 times faster than BA. Since changes in the expression of c-myc and c-jun occur minutes after exposure of the cells to the prodrug, these genes are likely to play a major role in the early stages of the differentiation pathway.

FEBS Letters 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