Category: 434-16-2

Tallman, Keri A.; Allen, Luke B.; Klingelsmith, Korinne; Anderson, Allison; Genaro-Mattos, Thiago C.; Mirnics, Karoly; Porter, Ned A.; Korade, Zeljka published the artcile< Prescription Medications Alter Neuronal and Glial Cholesterol Synthesis>, Recommanded Product: (3S,9S,10R,13R,14R,17R)-10,13-Dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol, the main research area is drug toxicity placenta blood brain barrier cholesterol neurodevelopmental disorder; antipsychotic antidepressant antiarrhythmic neuron astrocyte dehydrocholesterol DHCR7 enzyme; 7-DHC; DHCR7; DMG method; cholesterol; desmosterol; pharmaceuticals.

Mouse brain contains over 100 million neuronal, glial, and other support cells. Developing neurons and astrocytes synthesize their own cholesterol, and disruption of this process can occur by both genetic and chem. mechanisms. In this study we have exposed cultured murine neurons and astrocytes to six different prescription medications that cross the placenta and blood-brain barriers and analyzed the effects of these drugs on cholesterol biosynthesis by an LC-MS/MS protocol that assays 14 sterols and 7 oxysterols in a single run. Three antipsychotics (haloperidol, cariprazine, aripiprazole), two antidepressants (trazodone and sertraline), and an antiarrhythmic (amiodarone) inhibited one or more sterol synthesis enzymes. The result of the exposures was a dose-dependent increase in levels of various sterol intermediates and a decreased level of cholesterol in the cultured cells. Four prescription medications (haloperidol, aripiprazole, cariprazine, and trazodone) acted primarily on the DHCR7 enzyme. The result of this exposure was an increase in 7-dehydrocholesterol in neurons and astrocytes to levels that were comparable to those found in cultured neurons and astrocytes from transgenic mice that carried a Dhcr7 pathogenic mutation modeling the neurodevelopmental disorder Smith-Lemli-Opitz syndrome.

ACS Chemical Neuroscience published new progress about Antiarrhythmics. 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Recommanded Product: (3S,9S,10R,13R,14R,17R)-10,13-Dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Tallman, Keri A.; Allen, Luke B.; Klingelsmith, Korinne; Anderson, Allison; Genaro-Mattos, Thiago C.; Mirnics, Karoly; Porter, Ned A.; Korade, Zeljka published the artcile< Prescription Medications Alter Neuronal and Glial Cholesterol Synthesis>, Recommanded Product: (3S,9S,10R,13R,14R,17R)-10,13-Dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol, the main research area is drug toxicity placenta blood brain barrier cholesterol neurodevelopmental disorder; antipsychotic antidepressant antiarrhythmic neuron astrocyte dehydrocholesterol DHCR7 enzyme; 7-DHC; DHCR7; DMG method; cholesterol; desmosterol; pharmaceuticals.

Mouse brain contains over 100 million neuronal, glial, and other support cells. Developing neurons and astrocytes synthesize their own cholesterol, and disruption of this process can occur by both genetic and chem. mechanisms. In this study we have exposed cultured murine neurons and astrocytes to six different prescription medications that cross the placenta and blood-brain barriers and analyzed the effects of these drugs on cholesterol biosynthesis by an LC-MS/MS protocol that assays 14 sterols and 7 oxysterols in a single run. Three antipsychotics (haloperidol, cariprazine, aripiprazole), two antidepressants (trazodone and sertraline), and an antiarrhythmic (amiodarone) inhibited one or more sterol synthesis enzymes. The result of the exposures was a dose-dependent increase in levels of various sterol intermediates and a decreased level of cholesterol in the cultured cells. Four prescription medications (haloperidol, aripiprazole, cariprazine, and trazodone) acted primarily on the DHCR7 enzyme. The result of this exposure was an increase in 7-dehydrocholesterol in neurons and astrocytes to levels that were comparable to those found in cultured neurons and astrocytes from transgenic mice that carried a Dhcr7 pathogenic mutation modeling the neurodevelopmental disorder Smith-Lemli-Opitz syndrome.

ACS Chemical Neuroscience published new progress about Antiarrhythmics. 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Recommanded Product: (3S,9S,10R,13R,14R,17R)-10,13-Dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Capell-Hattam, Isabelle M.; Sharpe, Laura J.; Qian, Lydia; Hart-Smith, Gene; Prabhu, Anika V.; Brown, Andrew J. published the artcile< Twin enzymes, divergent control: the cholesterogenic enzymes DHCR14 and LBR are differentially regulated transcriptionally and post-translationally>, Safety of (3S,9S,10R,13R,14R,17R)-10,13-Dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol, the main research area is human cholesterol biosynthesis enzyme DHCR14 LBR post translational regulation; dehydrocholesterol reductase DHCR14 human regulation lamin B receptor LBR; DHCR14; LBR; TM7SF2; cholesterol; cholesterol regulation; endoplasmic reticulum-associated protein degradation (ERAD); enzyme degradation; protein degradation.

Cholesterol synthesis is a tightly regulated process, both transcriptionally and post-translationally. Transcriptional control of cholesterol synthesis is relatively well-understood. However, of the ~20 enzymes in cholesterol biosynthesis, post-translational regulation has only been examined for a small number Three of the four sterol reductases in cholesterol production, 7-dehydrocholesterol reductase (DHCR7), 14-dehydrocholesterol reductase (DHCR14), and lamin-B receptor (LBR), share evolutionary ties with a high level of sequence homol. and predicted structural homol. DHCR14 and LBR uniquely share the same Δ-14 reductase activity in cholesterol biosynthesis, yet little is known about their post-translational regulation. We have previously identified specific modes of post-translational control of DHCR7, but it is unknown whether these regulatory mechanisms are shared by DHCR14 and LBR. Using CHO-7 cells stably expressing epitope-tagged DHCR14 or LBR, we investigated the post-translational regulation of these enzymes. We found that DHCR14 and LBR undergo differential post-translational regulation, with DHCR14 being rapidly turned over, triggered by cholesterol and other sterol intermediates, whereas LBR remained stable. DHCR14 is degraded via the ubiquitin-proteasome system, and we identified several DHCR14 and DHCR7 putative interaction partners, including a number of E3 ligases that modulate DHCR14 levels. Interestingly, we found that gene expression across an array of human tissues showed a neg. relationship between the C14-sterol reductases; one enzyme or the other tends to be predominantly expressed in each tissue. Overall, our findings indicate that whereas LBR tends to be the constitutively active C14-sterol reductase, DHCR14 levels are tunable, responding to the local cellular demands for cholesterol.

Journal of Biological Chemistry published new progress about Follicular fluid. 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Safety of (3S,9S,10R,13R,14R,17R)-10,13-Dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

St. Clair, Johnna Wellman; London, Erwin published the artcile< Effect of sterol structure on ordered membrane domain (raft) stability in symmetric and asymmetric vesicles>, Application of C27H44O, the main research area is sterol structure ordered membrane domain lipid raft stability; FRET; Lipid asymmetry; Liquid ordered; Steroid; Sterol.

Sterol structure influences liquid ordered domains in membranes, and the dependence of biol. functions on sterol structure can help identify processes dependent on ordered domains. In this study we compared the effect of sterol structure on ordered domain formation in sym. vesicles composed of mixtures of sphingomyelin, 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and cholesterol, and in asym. vesicles in which sphingomyelin was introduced into the outer leaflet of vesicles composed of DOPC and cholesterol. In most cases, sterol behavior was similar in sym. and asym. vesicles, with ordered domains most strongly stabilized by 7-dehydrocholesterol (7DHC) and cholesterol, stabilized to a moderate degree by lanosterol, epicholesterol and desmosterol, and very little if at all by 4-cholesten-3-one. However, in asym. vesicles desmosterol stabilized ordered domain almost as well as cholesterol, and to a much greater degree than epicholesterol, so that the ability to support ordered domains decreased in the order 7-DHC > cholesterol > desmosterol > lanosterol > epicholesterol > 4-cholesten-3-one. This contrasts with values for intermediate stabilizing sterols in sym. vesicles in which the ranking was cholesterol > lanosterol ∼ desmosterol ∼ epicholesterol or prior studies in which the ranking was cholesterol ∼ epicholesterol > lanosterol ∼ desmosterol. The reasons for these differences are discussed. Based on these results, we re-evaluated our prior studies in cells and conclude that endocytosis levels and bacterial uptake are even more closely correlated with the ability of sterols to form ordered domains than previously thought, and do not necessarily require that a sterol have a 3β-OH group.

Biochimica et Biophysica Acta, Biomembranes published new progress about Bilayer biological membrane. 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Application of C27H44O.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Yamaji-Hasegawa, Akiko; Murate, Motohide; Inaba, Takehiko; Dohmae, Naoshi; Sato, Masayuki; Fujimori, Fumihiro; Sako, Yasushi; Greimel, Peter; Kobayashi, Toshihide published the artcile< A novel sterol-binding protein reveals heterogeneous cholesterol distribution in neurite outgrowth and in late endosomes/lysosomes>, Recommanded Product: (3S,9S,10R,13R,14R,17R)-10,13-Dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol, the main research area is cholesterol affinity neurite outgrowth endosome endocytosis; Endocytosis; Lipid domains; Lipid imaging; Lipid-binding protein; Membrane lipids.

We identified a mushroom-derived protein, maistero-2 that specifically binds 3-hydroxy sterol including cholesterol (Chol). Maistero-2 bound lipid mixture in Chol-dependent manner with a binding threshold of around 30%. Changing lipid composition did not significantly affect the threshold concentration EGFP-maistero-2 labeled cell surface and intracellular organelle Chol with higher sensitivity than that of well-established Chol probe, D4 fragment of perfringolysin O. EGFP-maistero-2 revealed increase of cell surface Chol during neurite outgrowth and heterogeneous Chol distribution between CD63-pos. and LAMP1-pos. late endosomes/lysosomes. The absence of strictly conserved Thr-Leu pair present in Chol-dependent cytolysins suggests a distinct Chol-binding mechanism for maistero-2.

Cellular and Molecular Life Sciences published new progress about Affinity. 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Recommanded Product: (3S,9S,10R,13R,14R,17R)-10,13-Dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Duchow, Elizabeth G.; Duchow, Mark W.; Plum, Lori A.; DeLuca, Hector F. published the artcile< Vitamin D binding protein greatly improves bioactivity but is not essential for orally administered vitamin D>, Quality Control of 434-16-2, the main research area is vitaminD calcium homeostasis 7dehydrocholesterol; ultraviolet light; vitamin D; vitamin D binding protein.

Vitamin D3 is a prohormone that is essential for calcium homeostasis. It is naturally produced in the skin by UV-B (UVB) irradiation of 7-dehydrocholesterol. In the absence of skin production, vitamin D3 can also be obtained from oral sources. However, the actual biol. equivalence of naturally produced (i.e., UVB-irradiation of skin) and oral vitamin D3 has not been determined We previously identified a unique and specific transport mechanism for skin-generated vitamin D3 which requires vitamin D binding protein (DBP); a mechanism that differs from absorption and transport of oral vitamin D3. In the following report, we examined the impact of this difference on the biol. activity of vitamin D3. We report that UVB-generated vitamin D3 is more potent at raising serum calcium compared to oral vitamin D3, with the total biol. activity being twofold higher. By examining the excretion of radiolabeled vitamin D3 injected unbound or pre-bound by DBP, we attributed the increased activity of skin-generated vitamin D3 to a significant reduction in biliary excretion of DBP-bound vitamin D relative to unbound vitamin D. Thus, removal of vitamin D3 from the skin by the natural DBP system markedly improves biol. activity compared to that given orally.

Physiological Reports published new progress about Homeostasis, calcium. 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Quality Control of 434-16-2.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Tierney, Elaine; Remaley, Alan T.; Thurm, Audrey; Jager, Leah R.; Wassif, Christopher A.; Kratz, Lisa E.; Bailey-Wilson, Joan E.; Bukelis, Irena; Sarphare, Geeta; Jung, Eun Sol; Brand, Boudewien; Noah, Kelly K.; Porter, Forbes D. published the artcile< Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits>, Related Products of 434-16-2, the main research area is sterol lipid hypolipidemia apolipoprotein disorder autism adaptive functioning deficit.

An improved understanding of sterol and lipid abnormalities in individuals with autism spectrum disorder (ASD) could lead to personalized treatment approaches. Toward this end, in blood, we identified reduced synthesis of cholesterol in families with ≥2 children with ASD participating with the Autism Genetic Resource Exchange (AGRE), as well as reduced amounts of high-d. lipoprotein cholesterol (HDL), apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB), with 19.9% of the subjects presenting with apolipoprotein patterns similar to hypolipidemic clin. syndromes and 30% with either or both ApoA1 and ApoB less than the fifth centile. Subjects with levels less than the fifth centile of HDL or ApoA1 or ApoA1 + ApoB had lower adaptive functioning than other individuals with ASD, and hypocholesterolemic subjects had apolipoprotein deficits significantly divergent from either typically developing individuals participating in National Institutes of Health or the National Health and Nutrition Examination Survey III.

Translational Psychiatry published new progress about Apolipoprotein A-I Role: ANT (Analyte), ANST (Analytical Study). 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Related Products of 434-16-2.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Hayek, Simon; Bekaddour, Nassima; Besson, Laurie; Alves de Sousa, Rodolphe; Pietrancosta, Nicolas; Viel, Sebastien; Smith, Nikaia; Jacob, Yves; Nisole, Sebastien; Mandal, Rupasri; Wishart, David S.; Walzer, Thierry; Herbeuval, Jean-Philippe; Vidalain, Pierre-Olivier published the artcile< Identification of Primary Natural Killer Cell Modulators by Chemical Library Screening with a Luciferase-Based Functional Assay>, Electric Literature of 434-16-2, the main research area is innate immunity NK CD8 T cell luciferase myeloid leukemia; dextromethorphan; diphenhydramine; luciferase; natural killer cells; screening.

Natural killer (NK) cells are essential players of the innate immune response that secrete cytolytic factors and cytokines such as IFN-γ when contacting virus-infected or tumor cells. They represent prime targets in immunotherapy as defects in NK cell functions are hallmarks of many pathol. conditions, such as cancer and chronic infections. The functional screening of chem. libraries or biologics would greatly help identify new modulators of NK cell activity, but commonly used methods such as flow cytometry are not easily scalable to high-throughput settings. Here we describe an efficient assay to measure the natural cytotoxicity of primary NK cells where the bioluminescent enzyme NanoLuc is constitutively expressed in the cytoplasm of target cells and is released in co-culture supernatants when lysis occurs. We fully characterized this assay using either purified NK cells or total peripheral blood mononuclear cells (PBMCs), including some patient samples, as effector cells. A pilot screen was also performed on a library of 782 metabolites, xenobiotics, and common drugs, which identified dextrometorphan and diphenhydramine as novel NK cell inhibitors. Finally, this assay was further improved by developing a dual-reporter cell line to simultaneously measure NK cell cytotoxicity and IFN-γ secretion in a single well, extending the potential of this system.

SLAS Discovery published new progress about CD8-positive T cell. 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Electric Literature of 434-16-2.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Zhou, Wenxu; Fisher, Paxtyn M.; Vanderloop, Boden H.; Shen, Yun; Shi, Huazhong; Maldonado, Adrian J.; Leaver, David J.; Nes, W. David published the artcile< A nematode sterol C4α-methyltransferase catalyzes a new methylation reaction responsible for sterol diversity>, Application In Synthesis of 434-16-2, the main research area is C4alpha methyltransferase dinosterol Caenorhabditis review; 8(14)-lophenol; Caenorhabditis elegans • biosynthesis; evolution.

A review. Primitive sterol evolution plays an important role in fossil record interpretation and offers potential therapeutic avenues for human disease resulting from nematode infections. Recognizing that C4-Me stenol products [8(14)-lophenol] can be synthesized in bacteria while C4-Me stanol products (dinosterol) can be synthesized in dinoflagellates and preserved as sterane biomarkers in ancient sedimentary rock is key to eukaryotic sterol evolution. In this regard, nematodes have been proposed to convert dietary cholesterol to 8(14)-lophenol by a secondary metabolism pathway that could involve sterol C4 methylation analogous to the C2 methylation of hopanoids (radicle-type mechanism) or C24 methylation of sterols (carbocation-type mechanism). Here, we characterized dichotomous cholesterol metabolic pathways in Caenorhabditis elegans that generate 3-oxo sterol intermediates in sep. paths to lophanol (4-Me stanol) and 8(14)-lophenol (4-Me stenol). We uncovered alternate C3-sterol oxidation and Δ7 desaturation steps that regulate sterol flux from which branching metabolite networks arise, while lophanol/8(14)-lophenol formation is shown to be dependent on a sterol C4α-methyltransferse (4-SMT) that requires 3-oxo sterol substrates and catalyzes a newly discovered 3-keto-enol tautomerism mechanism linked to S-adenosyl-l-methionine-dependent methylation. Alignment-specific substrate-binding domains similarly conserved in 4-SMT and 24-SMT enzymes, despite minimal amino acid sequence identity, suggests divergence from a common, primordial ancestor in the evolution of Me sterols. The combination of these results provides evolutionary leads to sterol diversity and points to cryptic C4-Me steroidogenic pathways of targeted convergence that mediate lineage-specific adaptations.

Journal of Lipid Research published new progress about Caenorhabditis elegans. 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Application In Synthesis of 434-16-2.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Khazan, Negar; Kim, Kyu Kwang; Hansen, Jeanne N.; Singh, Niloy A.; Moore, Taylor; Snyder, Cameron W. A.; Pandita, Ravina; Strawderman, Myla; Fujihara, Michiko; Takamura, Yuta; Jian, Ye; Battaglia, Nicholas; Yano, Naohiro; Teramoto, Yuki; Arnold, Leggy A.; Hopson, Russell; Kishor, Keshav; Nayak, Sneha; Ojha, Debasmita; Sharon, Ashoke; Ashton, John M.; Wang, Jian; Milano, Michael T.; Miyamoto, Hiroshi; Linehan, David C.; Gerber, Scott A.; Kawar, Nada; Singh, Ajay P.; Tabdanov, Erdem D.; Dokholyan, Nikolay V.; Kakuta, Hiroki; Jurutka, Peter W.; Schor, Nina F.; Rowswell-Turner, Rachael B.; Singh, Rakesh K.; Moore, Richard G. published the artcile< Identification of a Vitamin-D Receptor Antagonist, MeTC7, which Inhibits the Growth of Xenograft and Transgenic Tumors In Vivo>, Formula: C27H44O, the main research area is vitamin D receptor antagonist MeTC7 antitumor.

Vitamin-D receptor (VDR) mRNA is overexpressed in neuroblastoma and carcinomas of lung, pancreas, and ovaries and predicts poor prognoses. VDR antagonists may be able to inhibit tumors that overexpress VDR. However, the current antagonists are arduous to synthesize and are only partial antagonists, limiting their use. Here, we show that the VDR antagonist MeTC7 (5)(I), which can be synthesized from 7-dehydrocholesterol (6) in two steps, inhibits VDR selectively, suppresses the viability of cancer cell-lines, and reduces the growth of the spontaneous transgenic TH-MYCN neuroblastoma and xenografts in vivo. The VDR selectivity of 5 against RXRα and PPAR-γ was confirmed, and docking studies using VDR-LBD indicated that 5 induces major changes in the binding motifs, which potentially result in VDR antagonistic effects. These data highlight the therapeutic benefits of targeting VDR for the treatment of malignancies and demonstrate the creation of selective VDR antagonists that are easy to synthesize.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Formula: C27H44O.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts