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匹莫迪韋

NMR下載 COA and HPLC MSDS下載
names：
Pimodivir
CAS號(hào)：
1629869-44-8
MDL Number： MFCD31382121
MF(分子式)： C20H19F2N5O2 MW(分子量)： 399.39
EINECS: Reaxys Number:
Pubchem ID:67286591 Brand:BIOFOUNT

匹莫迪韋(1629869-44-8,Pimodivir,VX-787)是A型流感病毒聚合酶復(fù)合物的聚合酶基礎(chǔ)蛋白2（PB2）亞基的口服生物可利用的非核苷抑制劑，具有潛在的抗病毒活性。給藥后，匹莫地韋占據(jù)PB2 的7-甲基GTP（m7GTP）結(jié)合位點(diǎn)，從而阻斷流感聚合酶復(fù)合物的奪帽活性并抑制病毒mRNA的合成。PB2是組成甲型流感病毒聚合酶復(fù)合物的三個(gè)亞基之一，它負(fù)責(zé)感染細(xì)胞核中病毒RNA（vRNA）基因組的復(fù)制和轉(zhuǎn)錄。

貨品編碼	規(guī)格	純度	價(jià)格 (￥)	現(xiàn)價(jià)(￥)	特價(jià)(￥)	庫(kù)存描述	數(shù)量	總計(jì) (￥)
YZM000729-5mg	5mg	99.04%	￥ 1569.00	￥ 1569.00		2-3天	- +	￥ 0.00
YZM000729-2mg	2mg	99.04%	￥ 965.25	￥ 965.25		2-3天	- +	￥ 0.00

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中文別名	匹莫迪韋(1629869-44-8);吡莫地韋;VX-787；VX 787；VX787; JNJ-872；JNJ 872；JNJ872；VRT-0928787; VRT 0928787；VRT0928787;吡莫地爾; （2S，3S）-3-（（5-氟-2-（5-氟-1H-吡咯并[2,3-b]吡啶-3-基）嘧啶-4-基）氨基）雙環(huán)[2.2.2 ]辛烷-2-羧酸;
英文別名	Pimodivir(1629869-44-8);VX-787;VX-787; VX 787; VX787; JNJ-872; JNJ 872; JNJ872; VRT-0928787; VRT 0928787; VRT0928787;pimodivir; (2S,3S)-3-((5-Fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylic Acid;
CAS號(hào)	1629869-44-8
Inchi	InChI=1S/C20H19F2N5O2/c21-11-5-12-13(7-24-17(12)23-6-11)18-25-8-14(22)19(27-18)26-16-10-3-1-9(2-4-10)15(16)20(28)29/h5-10,15-16H,1-4H2,(H,23,24)(H,28,29)(H,25,26,27)/t9?,10?,15-,16-/m0/s1
InchiKey	JGPXDNKSIXAZEQ-SBBZOCNPSA-N
分子式 Formula	C20H19F2N5O2
分子量 Molecular Weight	399.39
溶解度Solubility	生物體外In Vitro:DMSO溶解度100 mg/mL(250.38 mM;Need ultrasonic)
性狀	固體粉末,Power
儲(chǔ)藏條件 Storage conditions	存放在陰涼干燥處，短期（數(shù)天至數(shù)周）在0-4°C下，長(zhǎng)期（數(shù)月至數(shù)年）在-20°C下保存。

匹莫迪韋(1629869-44-8,Pimodivir,VX-787)實(shí)驗(yàn)注意事項(xiàng)：

1.實(shí)驗(yàn)前需戴好防護(hù)眼鏡，穿戴防護(hù)服和口罩，佩戴手套，避免與皮膚接觸。
2.實(shí)驗(yàn)過(guò)程中如遇到有毒或者刺激性物質(zhì)及有害物質(zhì)產(chǎn)生，必要時(shí)實(shí)驗(yàn)操作需要手套箱內(nèi)完成以免對(duì)實(shí)驗(yàn)人員造成傷害
3.實(shí)驗(yàn)后產(chǎn)生的廢棄物需分類存儲(chǔ)，并交于專業(yè)生物廢氣物處理公司處理，以免造成環(huán)境污染Experimental considerations:
1. Wear protective glasses, protective clothing and masks, gloves, and avoid contact with the skin during the experiment.
2. The waste generated after the experiment needs to be stored separately, and handed over to a professional biological waste gas treatment company to avoid environmental pollution.

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產(chǎn)品說(shuō)明	匹莫迪韋(1629869-44-8,Pimodivir,VX-787)是一種有效的可口服的甲型流感病毒聚合酶的抑制劑，通過(guò)抑制PB2亞基起作用
Introduction	匹莫迪韋(1629869-44-8,Pimodivir,VX-787)is an orally bioavailable inhibitor of influenza A virus polymerasesthrough interaction with the viralPB2subunit.
Application1	Pimodivir（VX-787）是一種可口服的甲型流感病毒聚合酶抑制劑，通過(guò)抑制PB2亞基作用。
Application2	已發(fā)現(xiàn)吡咯并吡啶衍生物VX-787是一種抗病毒藥，目前仍處于針對(duì)甲型流感病毒感染的II期試驗(yàn)中。
Application3

匹莫迪韋(1629869-44-8,Pimodivir,VX-787)藥理學(xué)：

Pimodivir是A型流感病毒聚合酶復(fù)合物的聚合酶基礎(chǔ)蛋白2（PB2）亞基的口服生物可利用的非核苷抑制劑，具有潛在的抗病毒活性。給藥后，匹莫地韋占據(jù)PB2 的7-甲基GTP（m7GTP）結(jié)合位點(diǎn)，從而阻斷流感聚合酶復(fù)合物的奪帽活性并抑制病毒mRNA的合成。PB2是組成甲型流感病毒聚合酶復(fù)合物的三個(gè)亞基之一，它負(fù)責(zé)感染細(xì)胞核中病毒RNA（vRNA）基因組的復(fù)制和轉(zhuǎn)錄。

警示圖
危險(xiǎn)性	warning
危險(xiǎn)性警示	Not available
安全聲明	H303吞入可能有害+H313皮膚接觸可能有害+H2413吸入可能對(duì)身體有害
安全防護(hù)	P264處理后徹底清洗+P280戴防護(hù)手套/穿防護(hù)服/戴防護(hù)眼罩/戴防護(hù)面具+P305如果進(jìn)入眼睛+P351用水小心沖洗幾分鐘+P338取出隱形眼鏡（如果有）并且易于操作,繼續(xù)沖洗+P337如果眼睛刺激持續(xù)+P2393獲得醫(yī)療建議/護(hù)理
備注	實(shí)驗(yàn)過(guò)程中防止吸入、食入，做好安全防護(hù)

Smee DF, et al. Activities of JNJ63623872 and GS 4071 against influenza A H1N1pdm and H3N2 virus infections in mice. Antiviral Res. 2016 Dec;136:45-50.

Fu Y, et al. JNJ872 inhibits influenza A virus replication without altering cellular antiviral responses. Antiviral Res. 2016 Sep;133:23-31.

Boyd MJ, et al. Isosteric replacements of the carboxylic acid of drug candidate VX-787: Effect of charge on antiviral potency and kinase activity of azaindole-based influenza PB2 inhibitors. Bioorg Me

Byrn RA, et al. Preclinical activity of VX-787, a first-in-class, orally bioavailable inhibitor of the influenza virus polymerase PB2 subunit. Antimicrob Agents Chemother. 2015 Mar;59(3):1569-82.

A Phase 2 Study of Pimodivir (JNJ-63623872) in Combination with Oseltamivir in Elderly and NonElderly Adults Hospitalized with Influenza A Infection: OPAL study PMID 32604406; The Journal of infectiou

匹莫迪韋(1629869-44-8,Pimodivir,VX-787)參考文獻(xiàn)：

1.Preclinical activity of VX-787, a first-in-class, orally bioavailable inhibitor of the influenza virus polymerase PB2 subunit.
Byrn RA;Jones SM;Bennett HB;Bral C;Clark MP;Jacobs MD;Kwong AD;Ledeboer MW;Leeman JR;McNeil CF;Murcko MA;Nezami A;Perola E;Rijnbrand R;Saxena K;Tsai AW;Zhou Y;Charifson PS Antimicrob Agents Chemother. 2015 Mar;59(3):1569-82. doi: 10.1128/AAC.04623-14. Epub 2014 Dec 29.

VX-787 is a novel inhibitor of influenza virus replication that blocks the PB2 cap-snatching activity of the influenza viral polymerase complex. Viral genetics and X-ray crystallography studies provide support for the idea that VX-787 occupies the 7-methyl GTP (m(7)GTP) cap-binding site of PB2. VX-787 binds the cap-binding domain of the PB2 subunit with a KD (dissociation constant) of 24 nM as determined by isothermal titration calorimetry (ITC). The cell-based EC50 (the concentration of compound that ensures 50% cell viability of an uninfected control) for VX-787 is 1.6 nM in a cytopathic effect (CPE) assay, with a similar EC50 in a viral RNA replication assay. VX-787 is active against a diverse panel of influenza A virus strains, including H1N1pdm09 and H5N1 strains, as well as strains with reduced susceptibility to neuraminidase inhibitors (NAIs). VX-787 was highly efficacious in both prophylaxis and treatment models of mouse influenza and was superior to the neuraminidase inhibitor, oseltamivir, including in delayed-start-to-treat experiments, with 100% survival at up to 96 h postinfection and partial survival in groups where the initiation of therapy was delayed up to 120 h postinfection.

2.Pimodivir treatment in adult volunteers experimentally inoculated with live influenza virus: a Phase IIa, randomized, double-blind, placebo-controlled study.
Trevejo JM;Asmal M;Vingerhoets J;Polo R;Robertson S;Jiang Y;Kieffer TL;Leopold L Antivir Ther. 2017 Dec 15. doi: 10.3851/IMP3212. [Epub ahead of print]

BACKGROUND: ;Pimodivir (formerly JNJ-63623872) is a novel, non-nucleoside polymerase complex inhibitor with in vitro activity against influenza A virus, including pandemic 2009 H1N1, H7N9, H5N1 strains as well as neuraminidase- and amantadine-resistant strains.;METHODS: ;Randomized, double-blind, placebo-controlled, Phase IIa study. Healthy volunteers (n=104) were inoculated with an influenza A/Wisconsin/67/2005 (H3N2) challenge virus. 72 received pimodivir and 32 placebo. Pimodivir was dosed for 5 days once daily from 24 h after viral inoculation at four dose levels: 100 mg, 400 mg, loading dose 900/600 mg and loading dose 1,200/600 mg.;RESULTS: ;Pimodivir significantly reduced viral shedding (area under the concentration versus time curve [AUC] measured by 50% tissue culture infective dose [TCID;50;] or qRT-PCR) versus placebo as measured by cell culture assay in the pooled analysis (Jonckheere-Terpstra dose-response trend test [P=0.036]). Reductions were observed in viral shedding (AUC, duration and peak measured by grade), influenza-like symptoms (AUC, duration and peak measured by grade) and clinical symptoms (duration and peak measured by grade) for all pimodivir groups versus placebo, significantly so for the 1,200/600 mg group.

3.JNJ872 inhibits influenza A virus replication without altering cellular antiviral responses.
Fu Y;Gaelings L;Söderholm S;Belanov S;Nandania J;Nyman TA;Matikainen S;Anders S;Velagapudi V;Kainov DE Antiviral Res. 2016 Sep;133:23-31. doi: 10.1016/j.antiviral.2016.07.008. Epub 2016 Jul 20.

JNJ-63623872 (formally known as VX-787; referred to here as JNJ872) is an orally bioavailable compound, which is in phase II clinical trials for the treatment of influenza A virus (IAV) infections. Here we show that JNJ872 inhibits at nanomolar concentrations the transcription of viral RNA in IAV-infected human macrophages by targeting a highly conserved site on the cap-snatching domain of influenza polymerase basic 2 protein (PB2). Furthermore, even lower concentrations of JNJ872 protected macrophages from IAV-mediated death when given in combination with 100 nM gemcitabine, which also attenuated transcription and replication of viral RNA. Importantly, treating human macrophages with JNJ872 allowed expression of many immune-related and other genes, involved in antiviral responses, such as indoleamine 2,3-dioxygenase 1 (IDO), and cytosolic 5'-nucleotidase 3A (NT5C3A). Moreover, our targeted metabolomics analysis indicate that treatment with JNJ782 did not interfere with metabolic responses to infection, which further supported our transcriptomics results. Thus, VX-737 alone or in combination with other drugs could be beneficial for treating IAV infected patients, because it would allow the development of antiviral responses and, thereby, protect individuals from current and future infections with closely related IAV strains.

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