Disease relevance of isobutyramide

• Oral isobutyramide reduces transfusion requirements in some patients with homozygous beta-thalassemia [1].
• The objectives of this study were to characterize the in vitro effects of sodium butyrate on human prostate cancer cell growth, PSA gene expression, and differentiation in the LNCaP tumor model and to determine whether tumor progression in vivo is delayed by isobutyramide, an orally bioavailable butyrate analogue with a longer half-life [2].
• Oral isobutyramide therapy in patients with thalassemia intermedia: results of a phase II open study [3].
• Isobutyramide therapy in patients with sickle cell anemia [4].
• OBJECTIVE: To examine the effect of isobutyramide synthesized in our laboratory on human and murine globin gene expression and to test cell toxicity of the drug [5].

High impact information on isobutyramide

• Apicidin was the most potent agent compared with other HDAC inhibitors (trichostatin A, MS-275, HC-toxin, suberoylanilide hydroxamic acid [SAHA]) and previously tested compounds (butyrate, phenylbutyrate, isobutyramide, hydroxyurea, 5-aza-cytidine), leading to a 10-fold stimulation of HbF expression at nanomolar to micromolar concentrations [6].
• Furthermore, docetaxel induced Bcl-2 phosphorylation in KoTCC-1/BH cells and combined treatment with isobutyramide and docetaxel synergistically inhibited the growth of KoTCC-1/BH cells both in vitro and in vivo [7].
• We used titration with the inhibitors tetramethylene sulphoxide and isobutyramide to assess quantitatively the importance of alcohol dehydrogenase in regulation of ethanol oxidation in rat hepatocytes [8].
• The emission decay kinetics of Trp-314 in strong, slowly exchanging, ternary complexes with NADH/isobutyramide, NAD/pyrazole, and NADH/dimethyl sulfoxide displays a markedly nonexponential character [9].
• The paramagnetic effects of Co(II) at the catalytic site on the relaxation rates of the methyl protons of isobutyramide at 100 and 220 MHz indicate that this analog binds at a site 9.1 A from the catalytic Co(II) [10].

Chemical compound and disease context of isobutyramide

• A pilot phase II open study on 12 patients with thalassemia intermedia (7 men, 5 women; age 31 +/- 2.0 years SE) treated with oral isobutyramide, a derivative of butyric acid (150 mg/kg body wt/day), was performed in order to evaluate the effect of this compound in stimulating hemoglobin F (HbF) production [3].

Biological context of isobutyramide

• The role of the structural Co(II), which is more distant from isobutyramide (9-11 A), may be that of a template for protein conformation changes [10].
• Hydrolysis of the isobutyramide 6c yielded the desired (+)-4 in high enantiomeric excess [11].
• Isobutyramide, an orally bioavailable butyrate analogue, stimulates fetal globin gene expression in vitro and in vivo [12].
• The Km,app values for cyclohexanone and the Kd,app for isobutyramide stay constant throughout a 48-h incubation, whereas the Vmax,app and the total number of inhibitor binding sites decrease [13].
• Pharmacokinetics and safety of single oral doses of VX-366 (isobutyramide) in healthy volunteers [14].

Anatomical context of isobutyramide

• Neither endogenous apoA1 mRNA nor transcriptional activity of the rat apoA1 gene promoter (from -474 to -7) were altered by sodium butyrate or isobutyramide (0.3 mM to 10 mM) in Hep G2 or Caco-2 cells [15].

Associations of isobutyramide with other chemical compounds

• Traces of two new alkamides, decen-2-oic acid isobutylamide ( 3) and decanoic acid isobutylamide ( 4), were identified by mass spectrometry [16].
• Butyramide and isobutyramide were weaker inhibitors of histone deacetylase than 4-phenylbutyrate and phenylacetate, which in turn were less effective than 3-bromopropionate and butyrate [17].
• In vitro neuropharmacological evaluation of piperovatine, an isobutylamide from Piper piscatorum (Piperaceae) [18].

Gene context of isobutyramide

• The effects of isobutyramide on LNCaP tumor growth and serum PSA levels in both intact and castrate male mice were compared to controls [2].
• Drosophila alcohol dehydrogenase is found not to form a ternary complex with NADH and isobutyramide [19].
• With 2.5 approximately 5 mmol/L isobutyramide, the induction of the human gamma-globin gene is even more effective than that of mouse alpha-globin gene [5].

Analytical, diagnostic and therapeutic context of isobutyramide

• Oral administration of isobutyramide significantly reduced the KoTCC-1/C tumor volume compared with the KoTCC-1/BH tumor volume in nude mice [7].
• The combination of castration and adjuvant isobutyramide was synergistic in delaying tumor progression [2].
• The half-life of isobutyramide in athymic mice was determined by gas chromatography to be 4 h [2].

References