MK-2048

製品コードS2765 バッチS276501

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₁H₂₁ClFN₅O₄
	分子量	461.87	CAS No.	869901-69-9
Solubility (25°C)*	体外	DMSO	9 mg/mL (19.48 mM)
		Water	Insoluble
		Ethanol	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	MK-2048 is a potent inhibitor of integrase (IN) and IN_R263K with IC50 of 2.6 nM and 1.5 nM, respectively.
in vitro	MK-2048 inhibits subtype B and subtype C integrase activities with IC50 of 75 nM and 80 nM, respectively. Disintegration is prevented by high concentrations of MK-2048 to a comparable extent with both subtype B and C enzymes. Mutation at the site of R263K slightly increases integrase susceptibility to MK-2048. G118R translates into a decrease in integrase activity and confers resistance to MK-2048. ^[2] MK-2048 inhibits S217H intasome with an IC50 of 900 nM. By contrast, MK2048 remains fully active against the N224H intasome with an IC50 of 25 nM. MK2048 displays substantially lower dissociation rates compared with raltegravir, another integrase inhibitor. ^[3] The subsequent selection of E138K partially restores replication capacity to approximately 13% of wt levels and increased resistance to MK-2048 to approximately 8-fold. MK-2048 is active against viruses resistant to RAL and EVG. Exposure to MK-2048 leads to the selection of G118R as a possible novel resistance mutation after 19 weeks. Continued pressure with MK-2048 subsequently leads to an additional substitution after 29 weeks at position E138K, within the IN gene. Although the G118R mutation alone confers only slight resistance to MK-2048 but not to RAL or EVG, its presence arouses a dramatic reduction in viral replication capacity compared to wild-type NL4-3. E138K both partially restores viral replication capacity and also contributes to increased levels of resistance against MK-2048. ^[4]

製品説明

MK-2048 is a potent inhibitor of integrase (IN) and IN_R263K with IC50 of 2.6 nM and 1.5 nM, respectively.

in vitro

MK-2048 inhibits subtype B and subtype C integrase activities with IC50 of 75 nM and 80 nM, respectively. Disintegration is prevented by high concentrations of MK-2048 to a comparable extent with both subtype B and C enzymes. Mutation at the site of R263K slightly increases integrase susceptibility to MK-2048. G118R translates into a decrease in integrase activity and confers resistance to MK-2048. ^[2] MK-2048 inhibits S217H intasome with an IC50 of 900 nM. By contrast, MK2048 remains fully active against the N224H intasome with an IC50 of 25 nM. MK2048 displays substantially lower dissociation rates compared with raltegravir, another integrase inhibitor. ^[3] The subsequent selection of E138K partially restores replication capacity to approximately 13% of wt levels and increased resistance to MK-2048 to approximately 8-fold. MK-2048 is active against viruses resistant to RAL and EVG. Exposure to MK-2048 leads to the selection of G118R as a possible novel resistance mutation after 19 weeks. Continued pressure with MK-2048 subsequently leads to an additional substitution after 29 weeks at position E138K, within the IN gene. Although the G118R mutation alone confers only slight resistance to MK-2048 but not to RAL or EVG, its presence arouses a dramatic reduction in viral replication capacity compared to wild-type NL4-3. E138K both partially restores viral replication capacity and also contributes to increased levels of resistance against MK-2048. ^[4]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	PM1 cells
	濃度	0.0256 nM to 2 μM
	反応時間	72 hours
	実験の流れ	A total of 7.5×10⁴ PM1 cells per well are infected with clonal NL4-3 virus containing the integrase mutations G118R, E138K, or G118R and E138K or with wild-type viruses (45 ng p24 virus per well) by spinoculation at 1,200 × g for 2 hours at 37 °C. Cells are washed twice to remove unbound virus and then resuspends in RPMI growth medium alone or containing various concentrations of MK-2048, ranging between 0.0256 nM and 2 μM. Experiments is performed, each in duplicate. Supernatant reverse transcriptase (RT) activity is measured at 72 hours postinfection as an indicator of virus replication. Data are normalized based on uninfected and no-drug controls included in each experiment. Viral replication capacity is determined in PM1 cells using the same methodology as that used to determine EC50s, by comparing levels of supernatant RT activity of each mutant virus to those of wild-type virus in the absence of MK-2048.

参考

[4] Bar-Magen T, et al. J Virol. 2010, 84(18), 9210-9216.

+ 展开

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：

Targeting the Integrated Stress Response Kinase GCN2 to Modulate Retroviral Integration [ Molecules, 2021, 26(17)5423]	PubMed: 34500856
Hyperactive CDK2 Activity in Basal-like Breast Cancer Imposes a Genome Integrity Liability that Can Be Exploited by Targeting DNA Polymerase ε [ Mol Cell, 2020, S1097-2765(20)30723-1]	PubMed: 33152268
Activation of PERK-ATF4-CHOP pathway as a novel therapeutic approach for efficient elimination of HTLV-1-infected cells. [ Blood Adv, 2020, 12;4(9):1845-1858]	PubMed: 32369565
Discovery of Novel Integrase Inhibitors Acting outside the Active Site Through High-Throughput Screening. [ Molecules, 2019, 24(20)]	PubMed: 31614773
Loss of ARID1A promotes proliferation, migration and invasion via the Akt signaling pathway in NPC [ Cancer Manag Res, 2019, 11:4931-4946]	PubMed: 31213911

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。