Raltegravir potassium

製品コードS5245 バッチS524501

化学情報

	Synonyms	MK-0518 potassium	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₀H₂₀FN₆O₅.K
	分子量	482.51	CAS No.	871038-72-1
Solubility (25°C)*	体外	DMSO	96 mg/mL (198.95 mM)
		Ethanol	10 mg/mL (20.72 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Raltegravir Potassium(MK-0518 potassium) is the orally bioavailable potassium salt of raltegravir, the first approved human immunodeficiency virus type 1 (HIV-1) integrase inhibitor.
in vitro	PFV IN carrying the S217H substitution is 10-fold less susceptible to Raltegravir with IC50 of 900 nM. PFV IN displays 10% of WT activity and is inhibited by Raltegravir with an IC50 of 200 nM, indicating a ~twofold decrease in susceptibility to the IN strand transfer inhibitor (INSTI) compared with WT IN. S217Q PFV IN is as sensitive to Raltegravir as the WT enzyme. ^[1] Raltegravir is metabolized by glucuronidation, not hepatically. Raltegravir has potent in vitro activity against HIV-1, with a 95% inhibitory concentration of 31?0 nM, in human T lymphoid cell cultures. Raltegravir is also active against HIV-2 when Raltegravir is tested in CEMx174 cells, with an IC95 of 6 nM. Raltegravir metabolism occurs primarily through glucuronidation. Drugs that are strong inducers of the glucuronidation enzyme, UGT1A1, significantly reduce Raltegravir concentrations and should not be used. Raltegravir exhibits weak inhibitory effects on hepatic cytochrome P450 activity. Raltegravir does not induce CYP3A4 RNA expression or CYP3A4-dependent testosterone 6-β-hydroxylase activity. ^[2] Raltegravir cellular permeativity is reduced in the presence of magnesium and calcium. ^[3] Raltegravir and related HIV-1 integrase (IN) strand transfer inhibitors (INSTIs efficiently block viral replication. ^[4] In acutely infected human lymphoid CD4+ T-cell lines MT-4 and CEMx174, SIVmac251 replication is efficiently inhibited by Raltegravir, which shows an EC90 in the low nanomolar range. ^[5]
in vivo	Raltegravir induces viro-immunological improvement of nonhuman primates with progressing SIVmac251 infection. One non-human primate shows an undetectable viral load following Raltegravir monotherapy. ^[5]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	Human MT-4 cells
	濃度	0.0001-1 μM
	反応時間	5 days
	実験の流れ	Human MT-4 cells are infected for 2 hours with the SIVmac251, HIV-1 (IIIB) and HIV-2 (CDC 77618) stocks at a multiplicity of infection of, approximately, 0.1. Cells are then washed three times in phosphate buffered saline, and suspended at 5 × 10⁵/mL in fresh culture medium (to primary cells 50 units/mL of IL-2 are added) in 96-well plates, in the presence or absence of a range of triplicate raltegravir concentrations (0.0001 μM -1 μM). Untreated infected and mock-infected controls are prepared too, in order to allow comparison of the data derived from the different treatments. Viral cytopathogeniciy in MT-4 cells is quantitated by the methyl tetrazolium (MTT) method (MT-4/MTT assay) when extensive cell death in control virus-infected cell cultures is detectable microscopically as lack of capacity to re-cluster. The capability of MT-4 cells to form clusters after infection. Briefly, clusters are disrupted by pipetting; and, after 2 hours of incubation at 37 ℃, the formation of new clusters is assessed by light microscopy (100 × magnification). Cell culture supernatants are collected for HIV-1 p24 and HIV-2/SIVmac251 p27 core antigen measurement by ELISA. In CEMx174-infected cell cultures, which show a propensity to form syncytia induced by the virus envelope glycoproteins, syncytia are counted, in blinded fashion, by light microscopy for each well at 5 days following infection.
動物実験	動物モデル	Indian Rhesus macaques
	投薬量	50 mg/kg or 100 mg/kg
	投与方法	Oral administration

参考

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Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Inhibition of Adipose Tissue Beiging by HIV Integrase Inhibitors, Dolutegravir and Bictegravir, Is Associated with Adipocyte Hypertrophy, Hypoxia, Elevated Fibrosis, and Insulin Resistance in Simian Adipose Tissue and Human Adipocytes [ Cells, 2022, 11(11)1841]	PubMed: 35681536
Reduction of CD8 T cell functionality but not inhibitory capacity by integrase inhibitors [ J Virol, 2022, JVI0173021]	PubMed: 35019724
Impact of combinations of clinically observed HIV integrase mutations on phenotypic resistance to integrase strand transfer inhibitors (INSTIs): a molecular study [ J Antimicrob Chemother, 2022, dkab498]	PubMed: 35061879
A synthetic resveratrol analog termed Q205 reactivates latent HIV-1 through activation of P-TEFb [ Biochem Pharmacol, 2021, 197:114901]	PubMed: 34971588
The human leukemia virus HTLV-1 alters the structure and transcription of host chromatin in cis [ Elife, 2018, 7e36245]	PubMed: 29941091
[ PLoS Pathog, 2018, ]	PubMed: 29470552
Influence of Biological Sex, Age, and HIV Status in an In Vitro Primary Cell Model of HIV Latency Using a CXCR4 Tropic Virus [ AIDS Res Hum Retroviruses, 2018, 34(9):769-777]	PubMed: 29926732
Vpr Promotes Macrophage-Dependent HIV-1 Infection of CD4+ T Lymphocytes. [ PLoS Pathog, 2015, 11(7):e1005054]	PubMed: 26186441
A multisystem investigation of raltegravir association with intestinal tissue: implications for pre-exposure prophylaxis and eradication. [ J Antimicrob Chemother, 2014, 69(12):3275-81]	PubMed: 25114168
In vitro and in vivo activities of AIC292, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor. [ Antimicrob Agents Chemother, 2013, 57(11):5320-9]	PubMed: 23959304

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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