Category: 122110-53-6

Tarasenko, Nataly published the artcileHistone deacetylase inhibitors: the anticancer, antimetastatic and antiangiogenic activities of AN-7 are superior to those of the clinically tested AN-9 (Pivanex), Product Details of C10H18O4, the publication is Clinical & Experimental Metastasis (2008), 25(7), 703-716, database is CAplus and MEDLINE.

Histone deacetylase inhibitory prodrugs that are metabolized to butyric acid and formaldehyde possess antineoplastic properties and low toxicity. We sought to characterize the antiangiogenic and antimetastatic activities of two lead prodrugs, pivaloyloxymethyl butyrate (AN-9) and butyroyloxymethyl-diethyl phosphate (AN-7) in murine cancer models. In the s.c. implanted human colon carcinoma HT-29 xenograft model AN-7, exhibited superior anticancer activity compared to AN-9, as was evident by the significantly greater inhibition of tumor growth and reduction of serum CEA. AN-7 was also more effective in reducing mean vessel d. (MVD) by 7-fold, bFGF, Ki-67 (7-fold) and HIF-1α in immunohistochem. stained tumor sections. Semi-quant. evaluation of the levels of bFGF, HDAC1 and HIF-1α by Western blot anal. showed a decrease in expression only in the tumors of mice treated with AN-7. The level of bFGF was reduced 3-fold in the tumor and that of TIMP1 was elevated (by 3-fold) in the serum of AN-7 treated mice. In a 4T1 metastatic breast carcinoma model, AN-7 inhibited the formation of lung lesions by 76% and AN-9 by 47%, further demonstrating the greater efficacy of AN-7 compared to AN-9 (P < 0.02). Both AN-7 and AN-9 exhibited antimetastatic and antiangiogenic activities by reducing vascularization, bFGF expression and HIF-1α. Yet, AN-7 was more potent than AN-9.

Clinical & Experimental Metastasis 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 C17H18N3NaO3S, Product Details of C10H18O4.

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

Zimra, Yael published the artcileUptake of pivaloyloxymethyl butyrate into leukemic cells and its intracellular esterase-catalyzed hydrolysis, Recommanded Product: (Pivaloyloxy)methyl butyrate, the publication is Journal of Cancer Research and Clinical Oncology (2000), 126(12), 693-698, database is CAplus and MEDLINE.

Pivaloyloxymethyl butyrate (AN-9), a butyric acid (BA) prodrug, exhibited low toxicity and significant anticancer activity in vitro and in vivo. The purpose of this study was to elucidate the basis for AN-9 increased anticancer activity compared to BA, by studying the uptake of BA and AN-9 into the cells. Methods: The uptake rate and level of [¹⁴C]-AN-9 and [¹⁴C]-BA, labeled on the carboxylic moiety of BA, into HL-60 and MEL leukemic cell lines was measured. The cells were filtered and the retained radioactivity was determined The dependence of the uptake on the activity of cellular esterases and membrane fluidity was investigated. Results: The uptake level in cells incubated with [¹⁴C]-AN-9 increased rapidly, peaked after 30 min in MEL and 1 h in HL-60 cells, and declined thereafter. This decline could be attributed to the hydrolysis of AN-9 by cellular esterases and catabolism of the released BA to CO₂. In cells pretreated with an esterase inhibitor and incubated with [¹⁴C]-AN-9, the reduction of radioactivity was less precipitous. In cells exposed to [¹⁴C]-BA, the intracellular radioactivity level was low and unaffected by treatment with an esterase inhibitor. The uptake of [¹⁴C]-AN-9 decreased significantly at 4° compared to that at 37°. Conclusion: The higher potency of AN-9 compared to BA could be at least partially attributed to the more rapid uptake of the lipophilic AN-9 and the release of BA in the cells.

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 C6H8O6, Recommanded Product: (Pivaloyloxy)methyl butyrate.

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

Ugarenko, Michal published the artcileABT-737 overcomes Bcl-2 mediated resistance to doxorubicin-DNA adducts, Product Details of C10H18O4, the publication is Biochemical Pharmacology (2010), 79(3), 339-349, database is CAplus and MEDLINE.

Doxorubicin is an anthracycline anticancer agent that functions primarily by inhibiting topoisomerase II, but also forms covalent DNA adducts depending on the cellular availability of formaldehyde. The combination of formaldehyde-releasing prodrugs (such as AN-9) with doxorubicin has been shown to result in synergistic doxorubicin-DNA adduct formation and synergistic apoptosis in HL-60 leukemic cells, offering the potential for lower concentrations of doxorubicin to be used clin. to minimize side-effects. However, the overexpression of Bcl-2 confers resistance to doxorubicin/AN-9 DNA adduct forming treatments, thus limiting the therapeutic potential of this drug combination. The small mol. inhibitor, ABT-737, which binds to and inhibits Bcl-2, Bcl-xL and Bcl-w, was used in combination with doxorubicin/AN-9 treatments to overcome resistance to doxorubicin-DNA adducts in Bcl-2 overexpressing HL-60 cells (HL-60/Bcl-2). The combination treatment of doxorubicin and AN-9 (and all single agent controls) failed to induce an apoptotic response in HL-60/Bcl-2 cells, however, the addition of low nanomolar (sub-lethal) concentrations of ABT-737 was able to greatly increase apoptosis levels. Various control compounds were used to demonstrate that the mechanism of cell kill in response to the triple treatment’ (doxorubicin, AN-9 and ABT-737) is dependent on DNA adduct formation. Therefore, the ability of ABT-737 to inhibit Bcl-2 renders previously resistant HL-60 cancer cells highly sensitive to doxorubicin-DNA adducts, leading to a classical apoptotic response. In conclusion, the data obtained provides promising evidence that the anticancer activity of doxorubicin-DNA adducts can be substantially enhanced in Bcl-2 overexpressing cancers with the use of the small mol. Bcl-2 inhibitor, ABT-737.

Biochemical 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 C12H10FeO4, Product Details of C10H18O4.

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

Mansour, Oula C. published the artcileAn evaluation of the interaction of pixantrone with formaldehyde-releasing drugs in cancer cells, Synthetic Route of 122110-53-6, the publication is Cancer Chemotherapy and Pharmacology (2022), 89(6), 773-784, database is CAplus and MEDLINE.

Pixantrone is a synthetic aza-anthracenedione currently used in the treatment of non-Hodgkins lymphoma. The drug is firmly established as a poison of the nuclear enzyme topoisomerase II, however, pixantrone can also generate covalent drug-DNA adducts following activation by formaldehyde. While pixantrone-DNA adducts form proficiently in vitro, little evidence is presently at hand to indicate their existence within cells. The mol. nature of these lesions within cancer cells exposed to pixantrone and formaldehyde-releasing prodrugs was characterized along with the cellular responses to their formation. In vitro crosslinking assays, [14C] scintillation counting analyses and alk. comet assays were applied to characterize pixantrone-DNA adducts. Flow cytometry, cell growth inhibition and clonogenic assays were used to measure cancer cell kill and survival. Pixantrone-DNA adducts were not detectable in MCF-7 breast cancer cells exposed to [14C] pixantrone (10-40μM) alone, however the addition of the formaldehyde-releasing prodrug AN9 yielded readily measurable levels of the lesion at ∼ 1 adduct per 10 kb of genomic DNA. Co-administration with AN9 completely reversed topoisomerase II-associated DNA damage induction by pixantrone yet potentiated cell kill by the drug, suggesting that pixantrone-DNA adducts may promote a topoisomerase II-independent mechanism of cell death. Pixantrone-DNA adduct-forming treatments generally conferred mild synergism in multiple cell lines in various cell death and clonogenic assays, while pixantrone analogs either incapable or relatively defective in forming DNA adducts demonstrated antagonism when combined with AN9. The features unique to pixantrone-DNA adducts may be leveraged to enhance cancer cell kill and may be used to guide the design of pixantrone analogs that generate adducts with more favorable anticancer properties.

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, Synthetic Route of 122110-53-6.

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

Cutts, Suzanne M. published the artcileFormaldehyde-releasing prodrugs in combination with adriamycin can overcome cellular drug resistance, Formula: C10H18O4, the publication is Oncology Research (2005), 15(4), 199-213, database is CAplus and MEDLINE.

The anticancer drug Adriamycin is widely used in cancer chemotherapy and is classified as a topoisomerase II inhibitor. However, in the presence of formaldehyde, Adriamycin also forms high levels of DNA adducts. In this study, a new series of butyric acid and formaldehyde-releasing drugs related to AN9 (pivaloyloxymethyl butyrate) was assessed for their ability to facilitate Adriamycin-DNA adduct formation in Adriamycin-sensitive and -resistant cell lines (HL60 and HL60/MX2; MES-SA and MES-SA/Dx5). Drugs that released two molar equivalents of formaldehyde per mol of prodrug were superior in their ability to enhance adduct formation compared to those that released one molar equivalent. Adduct formation (as assessed by binding of radiolabeled Adriamycin to genomic DNA) was always lower in the resistant cell lines compared to the sensitive cell lines. However, in growth inhibition experiments, prodrug combinations were able to overcome Adriamycin resistance to varying degrees, and the combination of Adriamycin with selected prodrugs that release two moles of formaldehyde totally overcame resistance in HL60/MX2 cells. These HL60-derived cells express altered levels of topoisomerase II and also express a mutant form of the enzyme. Combinations of Adriamycin with selected prodrugs that release one or two moles of formaldehyde partially overcame P-glycoprotein-mediated resistance in MES-SA/Dx5 cells. Formaldehyde-releasing prodrugs (as single agents) overcame both forms of resistance in the two resistant cell lines, demonstrating that they were not substrates of these resistance mechanisms. Collectively, these results suggest that changing the mechanism via which Adriamycin exerts its anticancer effect by dramatically increasing adduct levels (requiring coadministration of formaldehyde-releasing prodrugs) may be a useful means of cancer treatment, as well as for overcoming Adriamycin-induced resistance.

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, Formula: C10H18O4.

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

Popovtzer, Rachela published the artcileElectrochemical lab on a chip for high-throughput analysis of anticancer drugs efficiency, HPLC of Formula: 122110-53-6, the publication is Nanomedicine (New York, NY, United States) (2008), 4(2), 121-126, database is CAplus and MEDLINE.

We describe a new method for rapid, sensitive, and high-throughput detection of colon cancer cells’ response to differentiation therapy, using a novel electrochem. lab-on-a-chip system. Differentiation-inducing agents such as butyric acid and its derivatives were introduced to miniature colon cancer samples within the nanovolume chip chambers. The efficacy of each of the differentiation-inducing agents was evaluated by electrochem. detection of the cellular enzymic activity level, whereas reappearance of normal enzymic activity denotes effective therapy. The results demonstrate the ability to evaluate simultaneously multiplex drug effects on miniature tumor samples (∼15 cells) rapidly (5 min) and sensitively, with quant. correlation between cancer cells’ number and the induced current. The use of miniature anal. devices is of special interest in clin. relevant samples, in that it requires less tissue for diagnosis, and enables high-throughput anal. and comparison of various drug effects on one small tumor sample, while maintaining uniform biol. and environmental conditions.

Nanomedicine (New York, NY, 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, HPLC of Formula: 122110-53-6.

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

Marsh, Alexandra M. R. published the artcileHistone deacetylase inhibitors: recent outcomes from clinical trials and the implications for oncology treatment approaches, Product Details of C10H18O4, the publication is Clinical Investigation (London, United Kingdom) (2013), 3(6), 571-594, database is CAplus.

A review. Histone deacetylases play an important role in multiple processes, including gene expression, proliferation, apoptosis, cytoskeletal organization, migration and angiogenesis. Histone deacetylase inhibitors are able to induce cell death and growth arrest as targeted anticancer agents. While only two, vorinostat and romidepsin, are licensed in oncol., several have reached Phase III trials and many more are in Phase I and II. In addition to this, multiple novel drugs, including more targeted agents, are emerging from preclin. studies. This paper examines the outcomes of recent clin. trials in 11 key histone deacetylase inhibitors, both as monotherapy and in combination with other antitumor drugs. An overview of the advantages and disadvantages between the different classes and individual drugs is discussed, as well as a brief outlook on the future developments in the field.

Clinical Investigation (London, United Kingdom) 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

Hobdy, Erole published the artcileAN-9 (Titan), Recommanded Product: (Pivaloyloxy)methyl butyrate, the publication is Current Opinion in Investigational Drugs (Thomson Scientific) (2004), 5(6), 628-634, database is CAplus and MEDLINE.

A review. Titan is developing AN-9 for the potential treatment of various cancers. AN-9 is a histone deacetylase inhibitor analog of butyric acid that causes apoptosis of cancer cells through signaling cellular differentiation. In Mar. 2001, a phase I/II study involving patients with liver tumors was initiated. By Nov. 2001, enrollment had been completed in a second phase II study of refractory non-small-cell lung cancer (NSCLC). In June 2003, Titan began enrollment for a phase IIb trial of AN-9 in combination with docetaxel in patients with NSCLC.

Current Opinion in Investigational Drugs (Thomson Scientific) 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

Rabizadeh, E. published the artcilePivanex, a histone deacetylase inhibitor, induces changes in BCR-ABL expression and when combined with STI571, acts synergistically in a chronic myelocytic leukemia cell line, Computed Properties of 122110-53-6, the publication is Leukemia Research (2007), 31(8), 1115-1123, database is CAplus and MEDLINE.

Chronic myelogenous leukemia (CML) is associated with the high TK activity chimeric protein BCR-ABL, known to contribute to cell tumorigenicity, resistance to apoptosis and differentiation. STI571, the TK inhibitor, is the current treatment for CML. One possible approach to overcome STI571 resistance appearing in some cases, involves the combination of histone deacetylase inhibitors (HDI) and STI571. We demonstrated that in K562, the CML cell line, pivaloyloxymethyl butyrate (Pivanex)-induced apoptosis, differentiation and reduced BCR-ABL protein levels and that the combination of Pivanex with STI571 acted synergistically. These data suggest the possible benefit of combining this HDI with STI571 for treatment of CML.

Leukemia 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, Computed Properties of 122110-53-6.

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

Aparna Lakshmi, I. published the artcileHistone deacetylase inhibitors in cancer therapy: an update, Product Details of C10H18O4, the publication is International Journal of Pharmaceutical Sciences Review and Research (2011), 10(1), 38-44, database is CAplus.

A review. Histone deacetylase inhibitors (HDACi) are novel class of anti-neoplastic agents and they mostly act by enhancing acetylation of histones, and promotes uncoiling of chromatin and activation of a large number of genes implicated in the regulation of cell survival like proliferation, differentiation and apoptosis. Most of them are therapeutic targets for cancer, neurodegenerative diseases and a number of other disorders. The histone deacetylases (HDACs) can be divided into two families, which include a total of eleven enzymes. The Zn⁺² dependent HDAC family composed of class I (HDACs 1, 2, 3 and 8), class II a/b (HDACs 4, 5, 6, 7, 9 and 10), and class IV (HDAC 11) and (2) Zn⁺² independent NAD-dependent class III SIRT enzymes. Histone deacetylase inhibitors (HDACi) which are been investigated for their antitumor potency are of with different chem. structures i.e Short-chain fatty acids (e.g. sodium butyrare), phenylburyrare, valproic acid and (AN-9), Hydroxyaminic acids (SAHA, pyroxamide, TSA, oxamflarin and CHPAs), Synthetic benzamide derivatives (e.g., MS-275 and Cl-994), Cyclic tetrapeptides (such as depsipeptide, trapoxin and apicidin), Electrophilic ketones (trifluoromethylketone), and Miscellaneous (depudecin, SNDX-275 and isothiocyanates). HDACi can have multiple mechanisms of inducing transformed cell growth arrest and cell death. These HDAC substrates are directly or indirectly involved in numerous important cell pathways including control of gene expression, regulation of cell proliferation, differentiation, migration, and death. As a consequence, HDACi can have multiple mechanisms of inducing transformed cell growth arrest and cell death. HDACi can be used in combination with radiation therapy, antitubulin agents, topoisomerase I and II inhibitors etc.

International Journal of Pharmaceutical Sciences Review and 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