Disease relevance of Metasqualene

• We show here that treatment with Triparanol, a distal inhibitor of cholesterol biosynthesis, induced patterning defects of the autopod at high frequency, including pre-axial syndactyly and post-axial polydactyly, thus reproducing limb anomalies frequently observed in humans [1].
• Three of the ten Gli3 mutant mice treated with triparanol, which blocks hedgehog signalling upstream of the Gli transcription factors, developed synovial chondromatosis, compared with eight of ten control mice [2].
• Diazacholesterol and triparanol induced myotonia in rats achieved by single dose administration [3].
• Triparanol (Trp) is known to cause clinical features similar to those seen in myotonic dystrophy, including myotonia, cataract and baldness [4].
• The changes seen were dissimilar to those reported with the most commonly used class of hypolipidaemic agents in the clinic, the hydroxymethyl glutaryl coenzyme A (HMGCoA) reductase inhibitors but were reminiscent of those reported for the hypolipidaemic agent Triparanol. which was predictive of toxicity seen in man [5].

High impact information on Metasqualene

• We identified a variety of experimental drugs with nanomolar affinity for the human EBP (Ki = 0.5-14 nM) such as MDL28815, AY9944, triparanol, and U18666A [6].
• Gas liquid chromatography-mass spectrometry (GC-MS) profiling of the sterols in the serum of the dams and in extracted embryos shows that in addition to desmosterol Delta24 reductase inhibition the conversion of Delta8 to Delta7 unsaturated sterols is also blocked by Triparanol [7].
• The true rate of sterol synthesis in liver cells was determined by measurement of the weight of desmosterol produced over a given time period during incubations in the presence of triparanol [8].
• Calcium increase in mouse skeletal muscles by triparanol: a drug to induce myotonic dystrophy-like clinical manifestations [4].
• The sterol inhibitors miconazole, AMO 1618, CCC, and MER 29 increased both the incorporation of (14)C-IPP into artemisinin by cell-free extracts and the production of artemisinin in shoot cultures of ARTEMISIA ANNUA [9].

Chemical compound and disease context of Metasqualene

• Treatment with triparanol also causes desmosterol accumulation but in these rats myotonia is rarely observed [10].

Anatomical context of Metasqualene

• Triparanol [2-(4-chlorophenyl)-1-(4-diethylaminoethoxyphenyl)-1-p-tolylethanol] at a concentration of 2 micronm has no effect on the overall conversion of [2=14C]acetate into C27 sterols by isolated liver cells [11].
• Administration of iprindole and triparanol left the function of the adrenal cortex unaffected, while under chloroquine treatment an activation with time was observed [12].
• Drug absorption from the small intestine of the triparanol-treated rat in situ [13].
• Myeloid bodies formation in triparanol treated cultured cells [14].
• Functional and biochemical evidence of damage to enterocytes induced by triparanol: role of lysosomes and the effect of gluten-free diet [15].

Associations of Metasqualene with other chemical compounds

• Fatty acid metabolism in Paramecium. Oleic acid metabolism and inhibition of polyunsaturated fatty acid synthesis by triparanol [16].
• The absorption half-life of 14C-TA was 5.3 min in the controls, 10.8 min in the methotrexate-intoxicated, 7.5 min in the fasted, and 5.3 min in the triparanol-intoxicated rats [17].
• Absorption of morphine, butylscopolamine, mecamylamine and phenobarbitone from the small intestine of the triparanol-treated rat in situ [18].

Gene context of Metasqualene

• Glucagon inhibited neutral sterol secretion before and after triparanol administration [19].

Analytical, diagnostic and therapeutic context of Metasqualene

• Treatment with triparanol, an inhibitor of Hedgehog signaling, resulted in a 60% decrease in tumor volume, a 30% decrease in cellularity, and a 20% reduction in proliferation rate [20].

References