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この項目では、米国の模型メーカーについて説明しています。プロスタグランジン合成酵素については「シクロオキシゲナーゼ」を、シトクロムc酸化酵素については「シトクロムcオキシダーゼ」を、その他の「コックス」については「コックス」をご覧ください。 |
COX（コックス）はアメリカ合衆国の模型、玩具ブランド。1954年にコックス（Cox）社としてカリフォルニア州で創業され、1996年にコロラド州ペンローズにあるエステス インダストリーズに買収された。さらにエステス社が2010年にホビコ（Hobbico）に買収され、現在は傘下ブランドとして残っている。小型模型エンジンの分野では知名度が高く歴史がある。
歴史
1945年に機械工であるロイ・コックスは、カリフォルニア州プラセンシア（Placentia）で「L.M.コックス製造社（The L. M. Cox Manufacturing Co, Inc.）」を創業。コックスは父の自転車屋やその周辺で育ち、機械や部品への興味を持つようになった。創業当初は木製コルク銃の玩具を車庫で生産していた。素材に木を選んだ理由は戦時中で金属が不足していたためだった。
第2次大戦後、1947年に金属の不足が解消されると、ダイキャスト製のクルマの玩具を製造するようになる。この商品はダイキャスト製のウィップカー(テザーカー)と呼ばれ、ヒモで結ばれていてその周りを円を描く様に走る自動車だった。ニトロとガソリンを燃料とするテザーカーは0.6立方インチ（9.83cm3）の排気量のエンジンを搭載し、時速160キロの速度で走り、たちまち人気が出た。
コックスは戦後はUコン機向けの小型内燃機関の生産で成長し、1963年にはカリフォルニア州サンタアナに8万平方フィートの工場を建設した。数年のうちに3回拡張して22.5万平方フィートになり、スロットカー、モデルロケット、HOゲージの鉄道模型やチェーンソー用の1馬力のガソリンエンジンを生産した。特に高性能の超小型グローエンジン、TeeDee 01、02、PeeWee 02は同社の独壇場であり、049、051を含めて、フリーフライト機、C/L（Ｕコン）機、ラジコン機に搭載された。
ロイ・コックスは1969年に引退し、会社をホビー分野の複合企業体であるレジャー・ダイナミクス（Leisure Dynamics）社に売却した。凧と携帯無線機とヨーヨーが製造品目に追加された。1976年、エアトロニクスと提携して成長しつつあったラジコンに参入した。1983年までにレジャー・ダイナミクス社が経営難に陥り、049の設計者ウィリアム・セルツァーが地元の実業家と組みコックスを買い戻し経営する。新親会社エアロミル・エンジニアリング（Aeromil Engineering Company）はコックスの社名をコックス・ホビーズ（Cox Hobbies, Incorporated）社に変更した。
1996年、モデルロケットメーカーのエステス インダストリーズの傘下に入り、業務をコロラド州ペンローズに移す。この際、この分社名をコックス・モデルズ（Cox Models）に変更。2009年にエステスはコックス・モデルズの全ての旧製品在庫をアメリカ・カナダの個人客・企業に売却、その内の一企業が「Cox International」というウェブサイトを立ち上げ、在庫をネット販売している。
さらにエステスが2010年にイリノイ州のホビコ（Hobbico）に買収され、現在は傘下ブランドとして残っている。ホビコはラジコン機を含む過去のコックスモデルズの正式な「コックス」ブランド及び商品ラインナップの継承者だが、「Cox International」も現在、過去のラジコン機エンジンを復刻販売したり、パーツ等の販売を行なっている。
外部リンク
- コックス・モデルズ公式ウェブサイト（英語）
- The Virtual Cox Museum（英語）
- Cox HO-Scale Trains Resource（英語）
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この項目は、企業に関連した書きかけの項目です。この項目を加筆・訂正などしてくださる協力者を求めています（ウィキプロジェクト 経済）。 |
"COX" redirects here. For other meanings, see Cox (disambiguation).
| prostaglandin-endoperoxide synthase |
| Identifiers |
| EC number |
1.14.99.1 |
| CAS number |
9055-65-6 |
| Databases |
| IntEnz |
IntEnz view |
| BRENDA |
BRENDA entry |
| ExPASy |
NiceZyme view |
| KEGG |
KEGG entry |
| MetaCyc |
metabolic pathway |
| PRIAM |
profile |
| PDB structures |
RCSB PDB PDBe PDBsum |
| Gene Ontology |
AmiGO / EGO |
| Search |
| PMC |
articles |
| PubMed |
articles |
| NCBI |
proteins |
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| cyclooxygenase 1 |
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Crystallographic structure of prostaglandin H2 synthase-1 complex with flurbiprofen.[1]
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| Identifiers |
| Symbol |
PTGS1 |
| Alt. symbols |
COX-1 |
| Entrez |
5742 |
| HUGO |
9604 |
| OMIM |
176805 |
| PDB |
1CQE (RCSB PDB PDBe PDBj) |
| RefSeq |
NM_080591 |
| UniProt |
P23219 |
| Other data |
| EC number |
1.14.99.1 |
| Locus |
Chr. 9 q32-q33.3 |
| cyclooxygenase 2 |
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Cyclooxygenase-2 (Prostaglandin Synthase-2) in complex with a COX-2 selective inhibitor.[2]
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| Identifiers |
| Symbol |
PTGS2 |
| Alt. symbols |
COX-2 |
| Entrez |
5743 |
| HUGO |
9605 |
| OMIM |
600262 |
| PDB |
6COX (RCSB PDB PDBe PDBj) |
| RefSeq |
NM_000963 |
| UniProt |
P35354 |
| Other data |
| EC number |
1.14.99.1 |
| Locus |
Chr. 1 q25.2-25.3 |
Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (EC 1.14.99.1) that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane.
The abbreviation "COX" is more often encountered in medicine. In genetics, the "PTGS" symbol is officially used for the prostaglandin-endoperoxide synthase (cyclooxygenase) family of genes and proteins, because the stem "COX" was already used for the cytochrome c oxidase family of genes and proteins.
Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain. Non-steroidal anti-inflammatory drugs (NSAID), such as aspirin and ibuprofen, exert their effects through inhibition of COX. The names "prostaglandin synthase (PHS)" and "prostaglandin endoperoxide synthetase (PES)" are still used to refer to COX.
Contents
- 1 Pharmacology
- 1.1 Classical NSAIDs
- 1.2 Newer NSAIDs
- 1.3 Natural COX inhibition
- 1.4 Cardiovascular side-effects of COX inhibitors
- 2 See also
- 3 References
- 4 External links
Pharmacology
In terms of their molecular biology, COX-1 and COX-2 are of similar molecular weight, approximately 70 and 72 kDa, respectively, and having 65% amino acid sequence homology and near-identical catalytic sites. The most significant difference between the isoenzymes, which allows for selective inhibition, is the substitution of isoleucine at position 523 in COX-1 with valine in COX-2. The smaller Val523 residue in COX-2 allows access to a hydrophobic side-pocket in the enzyme (which Ile523 sterically hinders). Drug molecules, such as DuP-697 and the coxibs derived from it, bind to this alternative site and are considered to be selective inhibitors of COX-2.
Classical NSAIDs
See also: Mechanism of action of aspirin
The main COX inhibitors are the non-steroidal anti-inflammatory drugs (NSAIDs).
The classical COX inhibitors are not selective and inhibit all types of COX. The resulting inhibition of prostaglandin and thromboxane synthesis has the effect of reduced inflammation, as well as antipyretic, antithrombotic and analgesic effects. The most frequent adverse effect of NSAIDs is irritation of the gastric mucosa as prostaglandins normally have a protective role in the gastrointestinal tract. Some NSAIDs are also acidic which may cause additional damage to the gastrointestinal tract.
Newer NSAIDs
Selectivity for COX-2 is the main feature of celecoxib, rofecoxib, and other members of this drug class. Because COX-2 is usually specific to inflamed tissue, there is much less gastric irritation associated with COX-2 inhibitors, with a decreased risk of peptic ulceration. The selectivity of COX-2 does not seem to negate other side-effects of NSAIDs, most notably an increased risk of renal failure, and there is evidence that indicates an increase in the risk of heart attack, thrombosis, and stroke through an increase of thromboxane unbalanced by prostacyclin (which is reduced by COX-2 inhibition).[citation needed] Rofecoxib (brand name Vioxx) was withdrawn in 2004 because of such concerns. Some other COX-2 selective NSAIDs, such as celecoxib, and etoricoxib, are still on the market.
Natural COX inhibition
Culinary mushrooms, like maitake, may be able to partially inhibit COX-1 and COX-2.[3][4]
A variety of flavonoids have been found to inhibit COX-2.[5]
Fish oils contain a natural inhibitor of COX.[6]
Hyperforin has been shown to inhibit COX-1 around 3-18 times as much as aspirin.[7]
Calcitriol (vitamin D) significantly inhibits the expression of the COX-2 gene.[8]
Caution should be exercised in combining low dose aspirin with COX-2 inhibitors due to potential increased damage to the gastric mucosa. COX-2 is upregulated when COX-1 is suppressed with aspirin, which is thought to be important in enhancing mucosal defense mechanisms and lessening the erosion by aspirin.[9]
Cardiovascular side-effects of COX inhibitors
COX-2 inhibitors have been found to increase the risk of atherothrombosis even with short-term use. A 2006 analysis of 138 randomised trials and almost 150 000 participants[10] showed that selective COX-2 inhibitors are associated with a moderately increased risk of vascular events, mainly due to a twofold increased risk of myocardial infarction, and also that high-dose regimens of some traditional NSAIDs such as diclofenac and ibuprofen are associated with a similar increase in risk of vascular events.
Fish oils (e.g. cod liver oil) have been proposed as a reasonable alternative for the treatment of rheumatoid arthritis and other conditions as a consequence of the fact that they provide less cardiovascular risk than other treatments including NSAIDs.[6]
See also
- Arachidonic acid
- Cyclooxygenase 1
- Cyclooxygenase 2
- NSAID
- Discovery and development of COX-2 selective inhibitors
- COX-2 selective inhibitor
References
- ^ PDB 1CQE; Picot D, Loll PJ, Garavito RM (January 1994). "The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1". Nature 367 (6460): 243–9. doi:10.1038/367243a0. PMID 8121489.
- ^ PDB 6COX; Kurumbail RG, Stevens AM, Gierse JK, McDonald JJ, Stegeman RA, Pak JY, Gildehaus D, Miyashiro JM, Penning TD, Seibert K, Isakson PC, Stallings WC (1996). "Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents". Nature 384 (6610): 644–8. doi:10.1038/384644a0. PMID 8967954.
- ^ Zhang Y, Mills GL, Nair MG (December 2002). "Cyclooxygenase inhibitory and antioxidant compounds from the mycelia of the edible mushroom Grifola frondosa". J. Agric. Food Chem. 50 (26): 7581–5. doi:10.1021/jf0257648. PMID 12475274.
- ^ Zhang Y, Mills GL, Nair MG (2003). "Cyclooxygenase inhibitory and antioxidant compounds from the fruiting body of an edible mushroom, Agrocybe aegerita". Phytomedicine 10 (5): 386–90. doi:10.1078/0944-7113-00272. PMID 12834003.
- ^ O'Leary KA, de Pascual-Tereasa S, Needs PW, Bao YP, O'Brien NM, Williamson G (July 2004). "Effect of flavonoids and vitamin E on cyclooxygenase-2 (COX-2) transcription". Mutat. Res. 551 (1–2): 245–54. doi:10.1016/j.mrfmmm.2004.01.015. PMID 15225597.
- ^ a b Fish oil: what the prescriber needs to know by Leslie G Cleland, Michael J James, and Susanna M Proudman http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1526555/
- ^ Albert D, Zündorf I, Dingermann T, Müller WE, Steinhilber D, Werz O. (December 2002). "Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase". Biochemical Pharmacology. 15;64(12):1767-75. PMID: 12445866
- ^ Moreno J, Krishnan AV, Peehl DM, Feldman D. (July–August 2006). "Mechanisms of vitamin D-mediated growth inhibition in prostate cancer cells: inhibition of the prostaglandin pathway.". Anticancer Res. 26 (4A): 2525–2530. PMID 16886660.
- ^ Wallace JL (October 2008). "Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn't the stomach digest itself?". Physiol. Rev. 88 (4): 1547–65. doi:10.1152/physrev.00004.2008. PMID 18923189.
- ^ Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C (June 2006). "Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials". BMJ 332 (7553): 1302–8. doi:10.1136/bmj.332.7553.1302. PMC 1473048. PMID 16740558.
External links
- The Cyclooxygenase Protein
- Cyclooxygenase at the US National Library of Medicine Medical Subject Headings (MeSH)
- GONUTS Page: Cyclooxygenase
- Cyclooxygenase: Proteopedia, life in 3D
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Oxidoreductases: dioxygenases, including steroid hydroxylases (EC 1.14)
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| 1.14.11: 2-oxoglutarate |
- Prolyl hydroxylase
- Lysyl hydroxylase
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| 1.14.13: NADH or NADPH |
- Flavin-containing monooxygenase
- Nitric oxide synthase
- Cholesterol 7 alpha-hydroxylase
- Methane monooxygenase
- 3A4
- Lanosterol 14 alpha-demethylase
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| 1.14.14: reduced flavin or flavoprotein |
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| 1.14.15: reduced iron-sulfur protein |
|
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| 1.14.16: reduced pteridine (BH4 dependent) |
- Phenylalanine hydroxylase
- Tyrosine hydroxylase
- Tryptophan hydroxylase
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| 1.14.17: reduced ascorbate |
- Dopamine beta hydroxylase
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| 1.14.18-19: other |
- Tyrosinase
- Stearoyl-CoA desaturase-1
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| 1.14.99 - miscellaneous |
- Cyclooxygenase
- Heme oxygenase (HMOX1)
- Squalene monooxygenase
- 17A1
- 21A2
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- B
- enzm
- 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
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Metabolism: lipid metabolism - eicosanoid metabolism enzymes
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|
| Precursor |
- Phospholipase C
- Diacylglycerol lipase
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|
| Prostanoids |
- PGE synthase
- Prostaglandin-E2 9-reductase
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| Leukotrienes |
- 5-Lipoxygenase activating protein/Arachidonate 5-lipoxygenase
- LTA4 hydrolase (B4 synthesis)
- LTC4 synthase
- Gamma-glutamyl transpeptidase
- DPEP2
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| Ungrouped |
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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