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磷坦姆沙韋

NMR下載 COA and HPLC MSDS下載
names：
Fostemsavir
CAS號：
864953-29-7
MDL Number： MFCD23098796
MF(分子式)： C25H26N7O8P MW(分子量)： 583.49
EINECS:No data available Reaxys Number:No data available
Pubchem ID:11319217 Brand:BIOFOUNT

磷坦姆沙韋(864953-29-7,BMS-663068,Fostemsavir)是開發用于治療HIV-1感染的HIV-1附著抑制劑。它是BMS-626529的前藥，它與病毒包膜糖蛋白gp120結合并干擾病毒與細胞CD4受體的附著

貨品編碼	規格	純度	價格 (￥)	現價(￥)	特價(￥)	庫存描述	數量	總計 (￥)
YZM000663-5mg	5mg	99.57%	￥ 2156.00	￥ 2156.00		2-3天	- +	￥ 0.00
YZM000663-2mg	2mg	99.57%	￥ 1170.00	￥ 1170.00		2-3天	- +	￥ 0.00

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中文別名	磷坦姆沙韋(864953-29-7),（3-（（4-芐基-1-哌嗪基）（氧代）乙酰基）-4-甲氧基-7-（3-甲基-1H-1,2,4-三唑-1-基）-1H-吡咯并（2 ，3-c）吡啶-1-基）甲基磷酸二氫;1,2-乙二酮，1-（4-苯甲酰基-1-哌嗪基）-2-（4-甲氧基-7-（3-甲基-1H-1,2,4-三唑-1-基）-1-（（膦酰氧基）甲基）-1H-吡咯并（2,3-c）吡啶-3-基）-;
英文別名	Fostemsavir(864953-29-7),BMS-663068; BMS 663068;BMS663068;(3-((4-Benzoyl-1-piperazinyl)(oxo)acetyl)-4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo(2,3-c)pyridin-1-yl)methyl dihydrogen phosphate;1,2-Ethanedione, 1-(4-benzoyl-1-piperazinyl)-2-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1-((phosphonooxy)methyl)-1H-pyrrolo(2,3-c)pyridin-3-yl)-;
CAS號	864953-29-7
Inchi	InChI = 1S / C25H26N7O8P / c1-16-27-14-32（28-16）23-21-20（19（39-2）12-26-23）18（13-31（21）15-40- 41（36,37）38）22（33）25（35）30-10-8-29（9-11-30）24（34）17-6-4-3-5-7-17 / h3- 7,12-14H，8-11,15H2,1-2H3，（H2,36,37,38）
InchiKey	SWMDAPWAQQTBOG-UHFFFAOYSA-N
分子式 Formula	C25H26N7O8P
分子量 Molecular Weight	583.49
溶解度Solubility	生物體外In Vitro:DMSO溶解度≥ 100 mg/mL(171.38 mM)H2O : 20 mg/mL(34.28 mM;Need ultrasonic)*"≥" means soluble可溶, but saturation unknown溶解度未知.
性狀	固體粉末,Power
儲藏條件 Storage conditions	-20°C 3 years年 4°C 2 years年 / In solvent溶液中:-80°C 6 months月 -20°C 1 month月

磷坦姆沙韋(864953-29-7,BMS-663068,Fostemsavir)毒理性質：

磷坦姆沙韋(864953-29-7,BMS-663068,Fostemsavir)實驗注意事項：
1.實驗前需戴好防護眼鏡，穿戴防護服和口罩，佩戴手套，避免與皮膚接觸。
2.實驗過程中如遇到有毒或者刺激性物質及有害物質產生，必要時實驗操作需要手套箱內完成以免對實驗人員造成傷害
3.實驗后產生的廢棄物需分類存儲，并交于專業生物廢氣物處理公司處理，以免造成環境污染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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產品說明	磷坦姆沙韋(864953-29-7,BMS-663068,Fostemsavir)是BMS-626529的原藥,能結合gp120,抑制HIV-1與細胞CD4受體的結合。
Introduction	磷坦姆沙韋(864953-29-7,BMS-663068,Fostemsavir)is the phosphonooxymethyl prodrug of BMS26529. Fostemsavir is a novel attachment inhibitor that targetsHIVgp120 and prevents its binding to CD4+T cells.
Application1	BMS-626529（一種HIV-1附著抑制劑）的前藥。
Application2	Prodrug of BMS-626529, an HIV-1 attachment inhibitor.
Application3

磷坦姆沙韋(864953-29-7,BMS-663068,Fostemsavir)藥理學：

※BMS-663068是開發用于治療HIV-1感染的HIV-1附著抑制劑。; IC50值：;目標：HIVBMS-663068是BMS-626529的前藥，它與病毒包膜糖蛋白gp120結合并干擾病毒與細胞CD4受體的附著。在有或沒有利托那韋的情況下，連續8天使用BMS-663068會導致血漿HIV-1 RNA水平大幅下降，并且通常具有良好的耐受性。BMS-663068作為抗逆轉錄病毒療法聯合治療的一部分，需要進行長期的臨床試驗。

※Fostemsavir（BMS-663068）是一種實驗性HIV進入抑制劑，是temsavir（BMS-626529）的前藥，用于治療HIV感染。通過阻斷病毒的gp120受體，它可以防止病毒最初附著于宿主CD4 + T細胞并進入宿主免疫細胞。它的作用方法是第一個針對艾滋病毒的藥物。因為它針對病毒生命周期的不同步驟，所以它為具有對其他HIV藥物高度耐藥性的病毒個體提供了希望。由于gp120是病毒的高度保守區域，該藥物不太可能通過產生CD4無關病毒來增強自身抗藥性。

警示圖
危險性	warning
危險性警示	Not available
安全聲明	H303吞入可能有害+H313皮膚接觸可能有害+H2413吸入可能對身體有害
安全防護	P264處理后徹底清洗+P280戴防護手套/穿防護服/戴防護眼罩/戴防護面具+P305如果進入眼睛+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,繼續沖洗+P337如果眼睛刺激持續+P2393獲得醫療建議/護理
備注	實驗過程中防止吸入、食入，做好安全防護

Nowicka-Sans B, et al. In vitro antiviral characteristics of HIV-1 attachment inhibitor BMS-626529, the active component of the prodrug BMS-663068. Antimicrob Agents Chemother. 2012 Jul;56(7):3498-507

Effects of Temsavir, Active Moiety of Antiretroviral Agent Fostemsavir, on QT Interval: Results From a Phase I Study and an Exposure-Response Analysis PMID 32027457; Clinical and translational science

Model-Based Phase 3 Dose Selection for HIV-1 Attachment Inhibitor Prodrug BMS-663068 in HIV-1-Infected Patients: Population Pharmacokinetics/Pharmacodynamics of the Active Moiety, BMS-626529 PMID 2690

Inhibitors of HIV-1 Attachment: The Discovery and Development of Temsavir and its Prodrug Fostemsavir PMID 29271653; Journal of medicinal chemistry 2018 01; 61(1):62-80 Name matches: temsavir fostemsa

Pharmacokinetic interactions between BMS-626529, the active moiety of the HIV-1 attachment inhibitor prodrug BMS-663068, and ritonavir or ritonavir-boosted atazanavir in healthy subjects PMID 25870057

磷坦姆沙韋(864953-29-7,BMS-663068,Fostemsavir)參考文獻：

1.Model-Based Phase 3 Dose Selection for HIV-1 Attachment Inhibitor Prodrug BMS-663068 in HIV-1-Infected Patients: Population Pharmacokinetics/Pharmacodynamics of the Active Moiety, BMS-626529.
Landry I1, Zhu L1, Abu Tarif M1, Hruska M1, Sadler BM2, Pitsiu M3, Joshi S4, Hanna GJ1, Lataillade M4, Boulton DW1, Bertz RJ5. Antimicrob Agents Chemother. 2016 Apr 22;60(5):2782-9. doi: 10.1128/AAC.02503-15. Print 2016 May.

BMS-663068 is an oral prodrug of the HIV-1 attachment inhibitor BMS-626529, which prevents viral attachment to host CD4(+) T cells by binding to HIV-1 gp120. To guide dose selection for the phase 3 program, pharmacokinetic/pharmacodynamic modeling was performed using data from two phase 2 studies with HIV-1-infected subjects (n = 244). BMS-626529 population pharmacokinetics were described by a two-compartment model with first-order elimination from the central compartment, zero-order release of prodrug from the extended-release formulation into a hypothetical absorption compartment, and first-order absorption into the central compartment. The covariates of BMS-663068 formulation type, lean body mass, baseline CD8(+) T-cell percentage, and ritonavir coadministration were found to be significant contributors to intersubject variability. Exposure-response analyses showed a relationship between the loge-transformed concentration at the end of a dosing interval (Ctau) normalized for the protein binding-adjusted BMS-626529 half-maximal (50%) inhibitory concentration (PBAIC50) and the change in the HIV-1 RNA level from the baseline level after 7 days of BMS-663068 monotherapy.

2.Pharmacokinetic interactions between BMS-626529, the active moiety of the HIV-1 attachment inhibitor prodrug BMS-663068, and ritonavir or ritonavir-boosted atazanavir in healthy subjects.
Zhu L1, Hruska M2, Hwang C2, Shah V2, Furlong M2, Hanna GJ2, Bertz R2, Landry IS2. Antimicrob Agents Chemother. 2015 Jul;59(7):3816-22. doi: 10.1128/AAC.04914-14. Epub 2015 Apr 13.

BMS-663068 is a prodrug of BMS-626529, a first-in-class attachment inhibitor that binds directly to HIV-1 gp120, preventing initial viral attachment and entry into host CD4(+) T cells. This open-label, multiple-dose, four-sequence, crossover study addressed potential two-way drug-drug interactions following coadministration of BMS-663068 (BMS-626529 is a CYP3A4 substrate), atazanavir (ATV), and ritonavir (RTV) (ATV and RTV are CYP3A4 inhibitors). Thirty-six healthy subjects were randomized 1:1:1:1 to receive one of four treatment sequences with three consecutive treatments: BMS-663068 at 600 mg twice daily (BID), BMS-663068 at 600 mg BID plus RTV at 100 mg once daily (QD), ATV at 300 mg QD plus RTV at 100 mg QD (RTV-boosted ATV [ATV/r]), or BMS-663068 at 600 mg BID plus ATV at 300 mg QD plus RTV at 100 mg QD. Compared with the results obtained by administration of BMS-663068 alone, coadministration of BMS-663068 with ATV/r increased the BMS-626529 maximum concentration in plasma (Cmax) and the area under the concentration-time curve in one dosing interval (AUCtau) by 68% and 54%, respectively.

3.Safety and efficacy of the HIV-1 attachment inhibitor prodrug BMS-663068 in treatment-experienced individuals: 24 week results of AI438011, a phase 2b, randomised controlled trial.
Lalezari JP1, Latiff GH2, Brinson C3, Echevarría J4, Treviño-Pérez S5, Bogner JR6, Thompson M7, Fourie J8, Sussmann Pena OA9, Mendo Urbina FC10, Martins M11, Diaconescu IG12, Stock DA13, Joshi SR13, Hanna GJ14, Lataillade M13; AI438011 study team. Lancet HIV. 2015 Oct;2(10):e427-37. doi: 10.1016/S2352-3018(15)00177-0. Epub 2015 Sep 1.

BACKGROUND: BMS-663068 is an oral prodrug of BMS-626529, an attachment inhibitor that binds to HIV-1 gp120, blocking viral attachment to host CD4 cells. AI438011 is an ongoing trial investigating the efficacy, safety, and dose-response of BMS-663068 in treatment-experienced, HIV-1-infected patients. Herein we present the results of the primary analysis.

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