Disease relevance of AY-9944

• Niemann-Pick disease experimental model: sphingomyelinase reduction induced by AY-9944 [1].
• The inhibitory effect on chondrocyte hypertrophy was confirmed by the AY 9944-mediated decreased expression of collagen X [2].
• Restoration of immune response by a cationic amphiphilic drug (AY 9944) in vitro: a new approach To chemotherapy against human immunodeficiency virus type 1 [3].
• Brain sterols in the AY-9944 rat model of atypical absence seizures [4].
• Pituitary agenesis was the most constant element of holoprosencephaly when AY 9944 was administered on d 4 of gestation at two dosages, 50 or 75 mg/kg [5].

High impact information on AY-9944

• After 4 days, AY 9944 suppressed metatarsal growth and growth plate chondrocyte proliferation and hypertrophy [2].
• Lastly, AY 9944 decreased the expression of Ihh in the metatarsal growth plate [2].
• When rats were fed 0.1% (w/w) AY-9944 (in chow) for 14-days, a complete inhibition of DHCR activity and a significant reduction in serum total cholesterol level were observed [6].
• AY-9944 (AY) exacerbates chronic recurrent seizures in rats that are analogous to atypical absence epilepsy in humans [7].
• More than 60 different incubations were carried out with washed microsomes or the 10,000 g supernatant under aerobic or anaerobic conditions; some experiments included addition of cofactors, fenpropimorph (a Delta(8);-Delta(7) isomerase inhibitor), and/or AY-9944 (a Delta(7) reductase inhibitor) [8].

Chemical compound and disease context of AY-9944

• Serotonin depletion attenuates AY-9944-mediated atypical absence seizures [9].
• Treatment of Long Evans hooded rats during post-natal brain development with the cholesterol synthesis inhibitor, AY-9944 (AY) results in the occurrence of atypical absence seizures, which are frequent, recurrent, and life-long [10].
• Developing rats were injected intraperitoneally twice weekly with a combination of two hypocholesterolemic agents: trans-clomiphene 50 mg per kg body weight, and AY-9944, 5 mg per kg body weight [11].
• These include absence seizures induced by gamma-hydroxybutyrate (GHB), low dose pentylenetetrazole, penicillin, THIP, and AY-9944 [12].

Biological context of AY-9944

• Rat embryos explanted at gestation day 10 and cultured for 48 h in the presence of the Delta7 reductase inhibitor AY 9944 were used as a model to discriminate between the beneficial effect of supplementation with cholesterol and the deleterious effect of supplementation with 7-dehydrocholesterol [13].
• Compared to LH-induced resumption of meiosis in follicles, that induced by AY-9944 was much delayed [14].
• Thus, the resumption of meiosis induced by added MAS [Biol. Reprod. 61 (1999) 1362, Biol. Reprod. 64 (2001) 418] or presumed endogenous MAS accumulation by AY-9944, resulted in oocyte maturation with remarkably slower kinetics than observed with LH stimulation [15].
• Effects of drugs on cholesterol esterification in normal and Niemann-Pick type C fibroblasts: AY-9944, other cationic amphiphilic drugs and DMSO [16].
• Our study suggests that the effect of AY-9944 on lung lipid metabolism is more detrimental in OAP-exposed rats than the expected benefit of AY-9944's simultaneous reduction in adrenal cortical activity [17].

Anatomical context of AY-9944

• After 3 weeks, AY 9944 reduced the cumulative growth, tibial growth, and the tibial growth plate height of the rats [2].
• Results are discussed in relation to the amphiphilic properties of AY 9944 and CPZ and to the interaction of these drugs with membranes or other intracellular targets such as calmodulin [18].
• The highest percentage of holoprosencephalic fetuses was found when AY 9944 was given on the fourth day of gestation [19].
• Effect of AY 9944 and chlorpromazine on Concanavalin A-induced stimulation of human lymphocytes [18].
• Effect of hypocholesterolemic agents on central nervous system cholesterol biosynthesis. II. AY-9944 and AY-9944 plus zuclomiphene [20].

Associations of AY-9944 with other chemical compounds

• Estrogen-stimulated progesterone synthesis in rabbit corpora lutea in the presence of an inhibitor of cholesterol biosynthesis (AY-9944) [21].
• Experiment 2: Four hundred days after stopping AY-9944 treatment (P420), brain sterol levels had returned to normal levels, but the AY-induced SWD lasted twice as long as at P55 [4].
• Cultured cells available from one patient showed increased levels of the same two sterols, decreased synthesis of cholesterol, and a pattern of inhibition by triparanol and AY-9944 consistent with a deficiency of 3beta-hydroxysteroid-delta8,delta7-isomerase [22].
• The relationships between cholesterogenesis and the activity of HMG-CoA reductase of microsomes prepared with or without sodium fluoride, and between changes of cholesterogenesis and microsomal sterols were studied in the isolated rat liver perfused with or without oleic acid in the presence of AY-9944 [23].

Gene context of AY-9944

• AY 9944 caused a modest increase in hepatic HMG-CoA reductase activity [24].
• We sought to produce chronic, recurrent, medically refractory seizures by administration of the cholesterol biosynthesis inhibitor AY-9944 (AY) during postnatal development in rats exposed prenatally to MAM [25].
• Reduction of acid sphingomyelinase activity in human fibroblasts induced by AY-9944 and other cationic amphiphilic drugs [26].
• Evaluation of a nonisotopic technique for studies of in vivo cholesterol metabolism in mini-pigs using inhibition of 7-dehydrocholesterol reductase by AY 9944 [27].

Analytical, diagnostic and therapeutic context of AY-9944

• An animal model for this disease has been obtained from the offspring of pregnant rats treated with "distal" inhibitors of delta7-dehydrocholesterol reductase, AY-9944 or BM15766 [28].

References