Disease relevance of NSC65449

• Possible mechanism for species difference on the toxicity of pivalic acid between dogs and rats [1].

High impact information on NSC65449

• Prodrugs that liberate pivalate (trimethylacetic acid) after hydrolysis have been developed to improve the bioavailability of therapeutic candidates [2].
• The differences in the disposition of pivalic acid between dogs and rats may account for differences in the degree of skeletal muscle disorders [3].
• The safety of S-1108 and the pharmacokinetics of S-1006 and pivalic acid liberated from pivaloyloxymethyl ester of S-1108 were investigated [4].
• Inhibition experiments were performed with (R,S)-[1,2-(14)C(2)]-2-PPA (1 mM) incubated with hepatocytes in the presence or absence of trimethylacetic acid (2 mM) or (-)-borneol (1 mM) for the inhibition of 2-PPA-CoA formation and 2-PPA acyl glucuronidation, respectively [5].
• This study investigates the polymorphism of piroxicam ester with pivalic acid [6].

Chemical compound and disease context of NSC65449

• In a high dose toxicity study of pivalic acid (PA), PA caused skeletal muscle disorder in dog, and a significant increase of pivaloyl carnitine (PC) was observed in canine muscle, but not in rat muscle [1].

Biological context of NSC65449

• A comparison of the ocular disposition of the pivalic acid released by hydrolysis of dipivefrin and that of topically applied free pivalic acid showed that the released pivalic acid is not metabolized in the eye and is rapidly eliminated from the eye with no apparent sequestration in ocular tissues [7].
• In this study, administration of pivalic acid or its sodium salt was found to decrease the L-carnitine concentration in the epididymal lumen of the hamster; it also tested whether this decrease affected sperm cell motility, chromatin structure, or fertilizing capacity [8].

Anatomical context of NSC65449

• Cytotoxicity of pivalylphenylephrine and pivalic acid to corneal endothelium [9].
• The patient's mother was receiving an antibiotic containing a derivative of pivalic acid to treat a urinary tract infection [10].
• Results indicate that pivalic acid dendrites exhibit a subtle oscillatory behavior of the axial growth velocity near the tip, with a frequency component that is associated with the sidebranch formation process [11].
• Treatment with pivalic acid or sodium pivalate did not render male hamsters infertile although it appeared to reduce the fertilizing ability of their spermatozoa [8].

Associations of NSC65449 with other chemical compounds

• Dipivefrin, a diester of pivalic acid and epinephrine that is used in the treatment of glaucoma, has been shown to be hydrolyzed in the cornea, and the ocular pharmacokinetics of the active moiety, epinephrine, have been determined [7].
• The influence of pivalic acid (PIV), a compound often used to make pro-drugs, and of the structurally related trichloroacetic acid (TCA), on several hepatic and renal enzymes was investigated in Sprague-Dawley rats, following a 4-day treatment period [12].
• Pivaloylcarnitine percent in the liver was 2.8 +/- 0.6 in the pivalic acid-treated rat, 3.5 +/- 1.2 in the pivampicillin-treated rat and 1.3 +/- 0.4 in the control group [13].
• After injection of pivalic acid, pivaloylcarnitine calculated as percent of free carnitine and short-chain acylcarnitines amounted to (mean +/- SD) 1.1 +/- 0, 15.4 +/- 2.5, 33.4 +/- 0.7 and 37.5 +/- 1.5% in the heart and 1.2 +/- 0.2, 20.6 +/- 9.5, 29.8 +/- 7.6 and 22.5 +/- 1.6% in brown fat after 0, 0.5, 2 and 8 h, respectively [13].

Analytical, diagnostic and therapeutic context of NSC65449

• Provision of pivalic acid or its sodium salt (20 mM or 40 mM) in the drinking water of mature male golden hamsters for 30 days reduced (by 72%, 75%, and 83% in three experiments) the L-carnitine concentration of the cauda epididymidis but did not inhibit sperm chromatin condensation, as assessed by flow cytometry [8].

References