A combination of kinetic methods (primarily stopped-flow spectrometry) and computational modelling of the binding of hydroxamic acids to the active site of a model peroxidase (horseradish, LPO; myeloperoxidase, MPO) was used to provide insight into structure-function relationships of peroxidases.. Hydroxamic acids acted as inhibitors of the native state (E), by formation of an E-hydroxamic acid complex that prevents H2O2 from binding. Hydroxamic acids donate one proton and one electron to peroxidase intermediates (CI and CII) and are oxidised to a radical themselves.. It is likely that the proton of the hydroxamic acid group is transferred to the His residue via a H-bond network involving Pro139, His42, Arg38 in HRP and His109, Gln105, Asp108, Arg255 and Glu258 in LPO as the hydroxamic acid group of all substrates investigated was bound in the vicinity of these active site residues. However, ambiguity remains as to the precise mechanism of proton transfer.. Two mechanisms were proposed for ...
PRIMARY OBJECTIVES:. I. To evaluate the response rate in patients receiving SAHA for stage IV breast cancer.. SECONDARY OBJECTIVES:. I. Time to progression. II. Overall survival. III. Toxicity profile. IV. Assessment of potential biological correlates.. OUTLINE: This is a multicenter study.. Patients receive oral suberoylanilide hydroxamic acid twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.. After completion of study treatment, patients are followed for 8 weeks. ...
Purpose: Agents that target the epigenome demonstrate activity in breast cancer models. In preclinical studies, the histone deacetylase inhibitor vorinostat induces cell cycle arrest, apoptosis and differentiation. We evaluated biomarker modulation in breast cancer tissues obtained from women with newly-diagnosed invasive disease who received vorinostat and those who did not. Experimental Design: Tumor specimens were collected from 25 women who received up to 6 doses of oral vorinostat 300 mg twice daily and from 25 untreated controls in a non-randomized study. Candidate gene expression was analyzed by RT-PCR using the Oncotype DX® 21-gene assay, and by immunohistochemistry for Ki-67 and cleaved caspase-3. Matched samples from treated women were analyzed for gene methylation by QM-MSP. Wilcoxon non-parametric tests were used to compare changes in quantitative gene expression levels pre- and post-vorinostat with changes in expression in untreated controls, and changes in gene methylation between ...
Combination regimen with bevacizumab (BEV) and vorinostat is well tolerated in patients with recurrent glioblastoma.Treatment of recurrent glioblastoma remains challenging as this study and others attempt to improve progression‐free survival and overall survival with BEV‐containing regimens.Background.Recurrent glioblastoma (GBM; World Health Organization grade 4) continues to have a very poor prognosis. Bevacizumab (BEV) has been shown to improve progression‐free survival (PFS) in recurrent GBM and is approved by the U.S. Food and Drug Administration for the treatment of recurrent GBM. Combination regimens have been explored, and in this phase II nonrandomized trial, we evaluated the efficacy of BEV combined with histone deacetylase inhibitor vorinostat (VOR) in recurrent GBM.Materials and Methods.In this phase II, single‐center, nonrandomized study, subjects with recurrent GBM received BEV 10 mg/kg intravenously (IV) every 2 weeks combined with VOR 400 mg p.o. daily for 7 days on, 7 ...
In this study, we have demonstrated that the pan-HDI LAQ824, by inhibiting IL-10 and increasing the expression of B7.2 and the production of several proinflammatory mediators, induced inflammatory macrophages that effectively activate Ag-specific CD4+ T cells and restore the responsiveness of anergic T cells.. Among the above changes, the most striking effect of LAQ824 was its ability to inhibit the production of the immunosuppressive cytokine IL-10. Such an effect was also displayed by other members of the hydroxamic acid family like LBH589, TSA, and SAHA, but not by the more specific HDI MS-275, which mainly target class I HDACs. The central role of IL-10 in the establishment and maintenance of T cell anergy (34, 35, 42-44) prompted us to further investigate the underlying mechanism(s) by which these particular HDIs inhibit IL-10 production in macrophages.. The dynamic production of pro- and anti-inflammatory mediators at the site of Ag encounter has been shown to shape the initiation, ...
The synthesis of squaric acid N-hydroxylamide esters 5 and amides 6 from dimethyl squarate 2a is described. These derivatives are analogues of the naturally occurring iron(III) chelator hydroxamic acid. On the basis of a comparative reactivity study,
Number of responders is defined as the number of patients in the analysis population who have complete response (CR), partial response (PR), or hematologic improvement (HI) per International Working Group Response Criteria during the course of the study. Confirmation of CR or PR will require a second assessment performed 4 weeks or more after the initial assessment. Confirmation of HI will require a second assessment performed 8 weeks or more after the initial assessment. Number of non-responders is defined as the number of patients who did not achieve CR, PR or HI in the study ...
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el-Bayoumy K, Upadhyaya P, Desai DH, Amin S, Hoffmann D, Wynder EL. Effects of 1,4-phenylenebis(methylene)selenocyanate, phenethyl isothiocyanate, indole-3-carbinol, and d-limonene individually and in combination on the tumorigenicity of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in A/J mouse lung. Anticancer Res 1996; 16: 2709-12 ...
A compound of formula (I) wherein R1, R2 and Q are as defined above, useful in the treatment of a condition selected from the group consisting of arthritis, cancer, tissue ulceration, macular degeneration, restenosis, periodontal disease, epidermolysis bullosa, scleritis, and other diseases characterized by matrix metalloproteinase activity, AIDS, sepsis, septic shock and other diseases involving the production of TNF. In addition, the compounds of the present invention may be used in combination therapy with standard non-steroidal anti-inflammatory drugs (NSAIDS) and analgesics, and in combination with cytotoxic drugs such as adriamycin, daunomycin, cis-platinum, etoposide, taxol, taxotere and other alkaloids, such as vincristine, in the treatment of cancer.
This invention is in the field of antiinflammatory pharmaceutical agents and specifically relates to compounds, compositions and methods for treating disorders mediated by cyclooxygenase-2 or 5-lipoxygenase, such as inflammation. Compounds of particular interest are defined by Formula I wherein A, Y, R1, R2, R3, R4 and R5 are as defined in the specification.
books.google.comhttps://books.google.com/books/about/The_Rearrangement_of_Hydroxamic_Acids_Is.html?id=wBpDAAAAIAAJ&utm_source=gb-gplus-shareThe Rearrangement of Hydroxamic Acids Isomeric with Triphenyl-acethydroxamic Acid ... ...
The second line of evidence showing a role for epigenetic therapy in T-cell lymphoma is the activity of HDAC inhibitors. As of the recent approval of belinostat for PTCL, there are three approved agents of this class. Vorinostat was approved for CTCL, then romidepsin for CTCL and PTCL, and recently belinostat (82-87). These agents inhibit HDACs (erasers in Fig. 1), leading to an increase in the expression of genes that cause cell-cycle arrest or apoptosis. Vorinostat and belinostat are hydroxamic acid derivatives that inhibit both class I and II HDACs, whereas romidepsin is a cyclic peptide that inhibits primarily the class I HDACs. The class II HDACs deacetylate a number of cytoplasmic proteins, including Hsp90 and tubulin, which may play a role in HDAC inhibitor activity in some models. The activity of all three agents in T-cell lymphoma suggests that inhibition of the class I HDACs may be the decisive factor in this disease.. It has become increasingly clear that HDAC inhibitors have a more ...
The combination of the investigational histone deacetylase inhibitor panobinostat (Faridak) with bortezomib (Velcade) and dexamethasone was able to recapture responses in 34.5% of heavily pretreated, bortezomib-refractory patients with multiple myeloma in the phase II PANORAMA 2 trial. The 55 patients enrolled at 12 trial sites had a median of four prior regimens, including two prior regimens with bortezomib. The responses at the end of the first treatment phase cycles included 1 near-complete response and 18 partial responses. "An additional 10 patients achieved minimal response, for a clinical benefit rate of 52.7%," reported Paul G. Richardson, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston, and colleagues. The investigators published their results online in Blood.. "Responses in the remainder of patients consisted of stable disease in 20 patients (36.4%) and progressive disease in 3 patients (5.5%). Response could not be assessed in the remaining 3 patients (5.5%) due ...
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|p|Oxamflatin is a potent histone deacetylase inhibitor with IC50 value of 15.7 nM [1].|/p||p|Histone deacetylases (HADC) are a series of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone and make the histones to wrap the
Additional file 1: of PARP inhibitor veliparib and HDAC inhibitor SAHA synergistically co-target the UHRF1/BRCA1 DNA damage repair complex in prostate cancer cells
A number of HDAC inhibitors have been characterized both in vitro and in vivo (1, 11, 31), and some are being developed clinically to treat cancer (1, 11, 31, 40). Different HDAC inhibitors have displayed different selectivity against HDAC isoenzymes; for example, FK228 inhibits HDAC1 and HDAC2 but not HDAC4 or HDAC6 (41), and MS-275 is potent against HDAC1 and HDAC3 but not HDAC8 (42). Herein, we have described CRA-026440, a novel hydroxamic acid-based, broad-spectrum inhibitor of HDAC enzymes with potent antitumor activity in vitro and in vivo. CRA-026440 inhibited potently all of the HDACs tested with Ki values ranging from 4.1 to 20 nmol/L.. CRA-026440 inhibited the growth of a number of human tumor cell lines and nonneoplastic HUVEC in vitro. Growth inhibition was accompanied by changes in several known biomarkers of HDAC response. These biomarkers included the accumulation of acetylated histones and acetylated tubulin, the accumulation of the tumor suppressor protein p21Cip1/WAF1, and the ...
A total of nine patients with advanced solid tumors were treated. Median t max for belinostat was observed 10 min after the start of infusion. Concentrations of belinostat rapidly declined with a t 1/2 of 2.9 h. The mean fraction of belinostat excreted unchanged in urine was 0.926 %. The metabolites belinostat glucuronide and 3-ASBA represented the largest fractions of belinostat dose excreted in urine (30.5 and 4.61 %, respectively), while renal excretion appeared to be a minor route of elimination for the parent belinostat ...
HDACi are showing promise in the clinic as anticancer agents, particularly for the treatment of hematologic malignancies (1-3). A large number of HDACi have been synthesized or purified from natural sources and there are clear differences in the chemical composition of the different compounds and their relative affinities for different class I, II, and IV HDACs (1, 15, 16). Although HDACi have variously been shown to induce tumor cell apoptosis, inhibit cell cycle progression, augment antitumor immune responses, or suppress angiogenesis depending on the tumor cell type, concentration of HDACi used, or cellular context of the experiment, very few comparative studies aimed at identifying different molecular or biological activities of structurally diverse HDACi have been done to identify subtle yet potentially important unique activities of the different compounds.. Herein, we have directly compared the apoptotic activities of the cyclic tetrapeptide romidepsin with the hydroxamic acid oxamflatin ...
LBH 589 | HDAC inhibitor | NVP-LBH 589 | Panobinostat | LBH589 | NVP-LBH589 | CAS [404950-80-7] | Axon 1548 | Axon Ligand™ with >98% purity available from supplier Axon Medchem, prime source of life science reagents for your research
NF-κB inhibition increases chemosensitivity to trichostatin A-induced cell death of Ki-Ras-transformed human prostate epithelial cells / Osong Kwon; Kyong A Kim; Sun Ok Kim; Ryong Ha; Won Keun Oh; Min-Soo Kim; Hee-Sik Kim; G D Kim; J W Kim; M Jung; C H Kim; Jong Seog Ahn; Bo Yeon Kim , 2006 ...
Nanoscience can arrange minute molecular entities into nanometric patterns in an orderly manner using self-assembly protocols. Scientists at the Technical University of Munich (TUM) have functionalized a simple rod-like building block with hydroxamic acids at both ends. They form molecular networks that not only display the complexity and beauty of mono-component self-assembly on surfaces; they also exhibit exceptional properties.
Struc tural data of HsHDAC8 pointed out the purpose in the residue D101 in the two substrate and HDACi recognition, HsH DAC8D101A mutated enzyme was inactive on protein sub strates and binding efficiency to hydroxamate inhibitor was decreased.Provided that D101 is localized from the vicinity of T99 of TgHDAC3, these data further strengthen the hypoth esis of a direct inhibition of TgHDAC3 by FR235222 and therefore are steady with a function of T99 in the interactions with cy clopeptide inhibitors. T99A and T99I adjust amino acid polarity, its as a result tempting to speculate that polar inter actions on the rim of the lively web page assistance the binding to HDACis, as proposed by Vannini et al.We predict the binding efficiency of HDACis to TgHDAC3 will be diminished while in the T99A and T99I mutated versions of TgH DAC3. On the other hand, an impact of these mutations within the regula tion and or exercise of TgHDAC3 compensating the decrease in HDAC activity triggered by drug inhibition ...
Belinostat是一种有效的氧肟型组蛋白去乙酰化酶克制剂在临床前肿瘤模型的频谱和表示临. 床疗效仍是很早期的临床试验方案普遍的抗肿瘤活性。 Belinostat始终绝对良好的耐受性. 均如下四(从30分钟逐日输注48小时持续输注)跟口服给药,而且,因为不或只有稍微的. 骨髓毒性已经碰到过,它与在全部范畴内剂量的其余抗肿瘤剂组合的井。临床实验计划需. belinostat在医治抗癌医疗装备的终极地位,而后才干断定进一步推动 ...
Farydak (Panobinostat Capsules) may treat, side effects, dosage, drug interactions, warnings, patient labeling, reviews, and related medications including drug comparison and health resources.
Find information on Belinostat (Beleodaq) in Daviss Drug Guide including dosage, side effects, interactions, nursing implications, mechanism of action, half life, administration, and more. Davis Drug Guide PDF.
It could prove to be an effective neuromodulation target in the treatment of psychiatric conditions characterized by failure of extinction. Stomach cancer: surgical experience in the clinics of the Louvain University (UCL) 1969-1986 Inverse 1,2,3-triazole-1-yl-ethyl substituted hydroxamates as highly potent matrix ...
Saha K; Zhang J; Gupta A; Dave R; Yimen M; Zerhouni B; Nature Medicine, 2001, vol. 7, issue 1, p 65, ISSN 10788956. ISBN 10788956. ...
Mobil saha satış ve el terminali çözümleri konusunda Türkiyenin en köklü şirketlerinden Desnet, uzman kadrosu ve barındırdığı Dünyanın en iyi markalarıyla hizmet veriyor
An existing method of oxidation involving oxodiperoxo(hexamethylphosphoramide)molybdenum(VI) has been adapted for the direct conversion of phenacetin and related amides to their respective hydroxamic acids. The hydroxamic acids are initially isolated as their stable dioxomolybdenum(VI) salts, in which form they can conveniently be stored and from which they are readily liberated by ligand displacement. The hydroxamic acids are of interest as the suspected toxic metabolites of several related drugs. The Mo(VI) derivatives of two analgesics, phenacetin and acetanilide, have been characterized by single-crystal X-ray diffraction. The ligand environment about the Mo atom is a markedly distorted octahedron in each case, with the dioxo O atoms bonded cis to each other, while trans to these bonds the hydroxamate Mo-O bonds are elongated. There is no conjugation between the phenyl rings and the hydroxamic acid group. Crystal data: MoO2L2, space group P21/c, Z = 4, a = 12.350 (6) Å, b = 17.477 (3) Å, c = 10
In the present study, seven hydroxamic acid derivatives of nonsteroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, fenoprofen, ketoprofen, indomethacin and diclofenac) were found to possess significant antioxidant, radical scavenging and metal chelating activities. The most active antioxidant and radical scavenger was N-methylhydroxamic acid of diclofenac (ANT = 88.0 % and EC50 = 60.1 microg mL-1). The activity of the standard substance, butylated hydroxyanisole, in the two assays was ANT = 86.9 % and EC50 = 18.8 microg mL-1, respectively. Ibuproxam was the strongest iron chelator among investigated hydroxamic acids (EC50 = 255.6 microg mL-1), yet significantly weaker than the standard substance, EDTA (EC50 = 29.1 microg mL-1). It seems that different mechanism is involved in metal chelating activity than in antioxidant and radical scavenging activity. Antioxidant and radical scavenging activities may be connected with conjugation of the nitrogen lone electron pair with the ...
Thyroid cancer has been indicated to have a higher global proportion of DNA methylation and a decreased level of histone acetylation. Previous studies showed that histone gene reviser and epigenetic changes role significant parts in papillary and anaplastic thyroid cancer tumorigenesis. The goal of this research was to study the endoplasmic reticulum (ER) stress-mediated actions of the dominant histone deacetylase (HDAC) inhibitor, N-hydroxy-7-(2-naphthylthio) hepatonomide (HNHA), in thyroid cancer and to explore its effects on apoptotic cell death pathways. Experiments were achieved to conclude the effects of HNHA in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) cell lines and xenografts, as compared with two other established HDAC inhibitors (SAHA; suberoylanilide hydroxamic acid and TSA; trichostatin A). Apoptosis, which was induced by all HDAC inhibitors, was particularly significant in HNHA-treated cells, where noticeable B-cell lymphoma-2 (Bcl-2) suppression and caspase
TY - JOUR. T1 - A novel histone deacetylase inhibitor identified by high-throughput transcriptional screening of a compound library. AU - Su, Gloria H.. AU - Sohn, Taylor A.. AU - Ryu, Byungwoo. AU - Kern, Scott E.. PY - 2000/6/15. Y1 - 2000/6/15. N2 - Libraries of compounds are increasingly becoming commercially available for the use of individual academic laboratories. A high-throughput system based on a stably integrated transcriptional reporter was used to screen a library of random compounds to identify agents that conferred robust augmentation of a signal transduction pathway. A novel histone deacetylase (HDAC) inhibitor, termed scriptaid, conferred the greatest effect, a 12- to 18-fold augmentation. This facilitation of transcriptional events was generally applicable to exogenous gene constructs, including vital and cellular promoters, different cell lines and reporter genes, and stably integrated and transiently introduced sequences. Scriptaid did not interfere with a further induction ...
OBJECTIVE: Histone deacetylase inhibitors mediate a potent growth-inhibitory effect in cancer cells through induction of cell-cycle arrest and apoptosis. Moreover, these agents significantly induce transcriptional activation of nuclear factor kappaB, as well as p21 regulated by protein kinase C, and are thought to negatively influence the ability of histone deacetylase inhibitor to effectively mediate apoptosis. This study aimed to evaluate the effect of calphostin C (a protein kinase C inhibitor) on trichostatin A (a histone deacetylase inhibitor)-mediated upregulation of nuclear factor kappaB and p21 promotor transcriptional activity, as well as induction of apoptosis in lung and esophageal cancer cells.. METHODS: Cultured lung and esophageal cancer cells were treated with calphostin C and trichostatin A. Nuclear factor kappaB transcriptional activity was quantitated by using the nuclear factor kappaB-luciferase assay. Transcription of p21 gene and p21 protein levels was evaluated by using the ...
1. A compound of Formula Ib: ##STR00016## or a pharmaceutically acceptable salt thereof, wherein: R1 is selected from the group consisting of C1-6alkyl, C1-6substituted alkyl, C2-6alkenyl, C2-6substituted alkenyl, C2-6alkynyl, C2-6substituted alkynyl, C3-6cycloalkyl, C3-66substituted cycloalkyl, phenyl, cyano, hydroxyl, thiol, sulfonamide, amine, ##STR00017## X is oxygen or sulfur; X1 is O, S, --S(O)-- or --S(O)2--; W is oxygen or sulfur; R5 is selected from the group consisting of alkoxy, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl and substituted cycloalkenyl; R6 and R7 are each independently selected from the group consisting of hydrogen, C1-6alkyl, C1-6substituted alkyl, C2-6alkenyl, C2-6substituted alkenyl, C2-6alkynyl, C2-6substituted alkynyl, C3-6cycloalkyl, C3-66substituted cycloalkyl; or R6 and R7 are joined to form an C3-10-cycloalkyl; R8 is selected from the group consisting of hydrogen, ...
Histone deacetylases (HDACs) play a major role in chromatin remodeling, gene regulation, and cellular signaling. While the role of each class of HDAC during normal development is unclear, several HDAC inhibitors are embryotoxic; the mechanisms leading to the teratogenicity of HDAC inhibitors are not …
5045 Spiruchostatin A is a natural compound with structural similarity to the bicyclic tetrapeptide HDAC inhibitor FK228. FK228 shows specificity for class I HDACs and is in early phase clinical trials for cancer. We recently described a total synthesis of Spiruchostatin A raising the potential to optimise activity by generation of structural analogues. We present in-vitro characterization of Spiruchostatin A as a potent bicyclic class I HDAC inhibitor, with important differences in activity in malignant verses normal cells and pharmacodynamic differences to hydroxamate non-specific HDAC inhibitors. Spiruchostatin A induced potent inhibition of MCF7 breast cancer cell growth with an IC50 value of 6nM compared to 0.8nM, 44nM and 500nM for FK228, and the hydroxamates Trichostatin A (TSA) and Suberoylanilide Hydroxamic Acid (SAHA) respectively. In keeping with its structural similarity to bicyclic HDAC inhibitors, Spiruchostatin A induced protein acetylation, differentiation, G2M cell cycle arrest ...
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Triple-negative breast cancer (TNBC) is the most aggressive and invasive of the breast cancer subtypes. TNBC is a challenging disease that lacks targets for treatment. Histone deacetylase inhibitors (HDACi) are a group of targeted anticancer agents that enhance radiosensitivity. Bcl-2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) is a member of the Bcl-2 subfamily. BNIP3 is not found in normal breast tissue but is up-regulated in breast cancer. In the present study, we investigated the anti-cancer effects of a newly developed HDACi, YCW1, combined with ionizing radiation (IR) in TNBC in vitro and in an orthotopic mouse model. Furthermore, we examined the relationship between autophagy and BNIP3. Trypan blue exclusion was used to investigate the viability of 4 T1 (a mouse TNBC cell line) and MDA-MB-231 cells (a human TNBC cell line) following combined YCW1 and IR treatment. Flow cytometry was used to determine apoptosis and autophagy. The expression levels of BNIP3, endoplasmic reticulum
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Epigenetic alterations of the histone acetylation play an important role in the regulation of gene expression associated with cell cycles and apoptosis that may affect the chemosensitivity of gastric carcinomas. Recently, a histone deacetylase inhibitor, trichostatin A (TSA), was proven to be a chemo-sensitizer on human erythroleukemia cells. With the aim of improving the chemotherapeutic efficacy of gastric carcinoma, the effect of TSA on the chemosensitivity of several anticancer drugs in gastric carcinoma cells was investigated. Human gastric cancer cell lines, OCUM-8 and MKN-74, and 5 anticancer drugs, 5-fluorouracil (5-FU), paclitaxel (PTX), oxaliplatin (OXA), irinotecan (SN38) and gemcitabine (GEM) were used. In both gastric cancer cell lines, a synergistic anti-proliferative effect by the combination of TSA (30 ng/ml) with 5-FU, PTX or SN38 showed a synergistic anti-proliferative effect in OCUM-8 and MKN-74 cells. TSA increases the expression of p21, p53, DAPK-1 and the DAPK-2 gene in ...
Histone deacetylase (HDAC) inhibition is a novel entity in medical oncology, and several HDAC inhibitors are in clinical trials. One of them is the hydroxamic acid belinostat (PXD101) that has demonstrated therapeutic efficacy for several clinical indications. Acetylation of histones is a key event after treatment with HDAC inhibitors, and could thus be used as a marker for monitoring cellular response to HDAC inhibitor treatment. Here we describe the utility of a newly described monoclonal antibody against acetylated H4 for immunohistochemistry on paraffin-embedded fine needle biopsies from nude mice carrying A2780 human ovarian cancer xenografts. Acetylated H4 was monitored in vivo by immunohistochemistry during treatment with belinostat, and compared with pharmacokinetics in plasma and tumor tissue. We found an increased level of acetylated H4 15 min after a single treatment (200 mg/kg i.v.) with maximum level reached after 1 h. H4 acetylation intensity reflected the belinostat concentration ...
Background: Belinostat is a hydroxamic acid based pan-histone deacetylase (HDAC) inhibitor that inhibits Class I, II, and IV HDAC enzymes at micromolar concentrations; it (Beleodaq) was recently approved in the US for the treatment of relapsed/refractory PTCL. The excretion of belinostat and its metabolites has been studied using radiolabeled belinostat in dogs and rats (∼70% and 50% excreted fecally and 30% and 50% excreted renally, respectively). The renal excretion of parent belinostat was ,1% in both species.. Objective: To determine the excretion route of radiolabeled belinostat and its metabolites following single IV administration of 14C-labeled belinostat in patients with advanced cancers. Secondary objectives included an assessment of safety.. Methods: Patients with progressive or recurrent malignancies who failed standard therapies were eligible for the study. Patients with severe constipation, urinary incontinence, primary hepatic or renal carcinomas were excluded. Six eligible ...
Learn about the potential side effects of acetohydroxamic acid. Includes common and rare side effects information for consumers and healthcare professionals.
Learn about Lithostat (Acetohydroxamic Acid Tablets) may treat, uses, dosage, side effects, drug interactions, warnings, patient labeling, reviews, and related medications.
The bioactive metabolite of Substance P, the heptapeptide SP1-7 (H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH), has been shown to attenuate signs of hyperalgesia in diabetic mice, which indicate a possible use of compounds targeting the SP1-7 binding site as analgesics for neuropathic pain. Aiming at the development of drug-like SP1-7 peptidomimetics we have previously reported on the discovery of H-Phe-Phe-NH2 as a high affinity lead compound. Unfortunately, the pharmacophore of this compound was accompanied by a poor pharmacokinetic (PK) profile. Herein, further lead optimization of H-Phe-Phe-NH2 by substituting the N-terminal phenylalanine for a benzylcarbamate group giving a new type of SP1-7 analogues with good binding affinities is reported. Extensive in vitro as well as in vivo PK characterization is presented for this compound. Evaluation of different C-terminal functional groups, i.e., hydroxamic acid, acyl sulfonamide, acyl cyanamide, acyl hydrazine, and oxadiazole, suggested hydroxamic acid as a ...
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2(5H)-Furanone,3-[(2R)-2-hydroxy-7-[(2S,- 2S,5R,5S)-octahydro-5-[(1S,4Z)-1-hydroxy- 4-heptadecenyl][2,2-bifuran]-5-yl]heptyl]-5- methyl-,(5S)- (4-chlorophenyl) 3-phenyl-2-phenylmethoxycarbonylamino-propanoate 3-octanoyloxybutyl octanoate Arachidonate hydroxamic acid Calcium, N-(4-((4-(diethylamino)phenyl)(5-hydroxy-2,4-disulfophenyl)methylene)-2,5-cyclohexadien-1-ylidene)-N-ethylethanaminium hydroxide inner salt aluminum complexes 2-(2-methylbut-3-en-2-yl)phenol 1,1,2,2-Ethanetetracarboxylic 1,2:1,2-diimide 1,2,3,4,5-pentachloro-6-[(Z)-2-chloroethenyl]benzene Cobalt(2+) selenate Amberlite XE-64
TY - JOUR. T1 - Activation of the stress proteome as a mechanism for small molecule therapeutics. AU - Brose, Rebecca Deering. AU - Shin, Gloria. AU - Mcguinness, Martina C.. AU - Schneidereith, Tonya. AU - Purvis, Shirley. AU - Dong, Gao X.. AU - Keefer, Jeffrey. AU - Spencer, Forrest. AU - Smith, Kirby D.. PY - 2012/10. Y1 - 2012/10. N2 - Various small molecule pharmacologic agents with different known functions produce similar outcomes in diverse Mendelian and complex disorders, suggesting that they may induce common cellular effects. These molecules include histone deacetylase inhibitors, 4-phenylbutyrate (4PBA) and trichostatin A, and two small molecules without direct histone deacetylase inhibitor activity, hydroxyurea (HU) and sulforaphane. In some cases, the therapeutic effects of histone deacetylase inhibitors have been attributed to an increase in expression of genes related to the disease-causing gene. However, here we show that the pharmacological induction of mitochondrial ...