MK-2048Integrase inhibitor for HIV-1,second generation CAS# 869901-69-9 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 869901-69-9 | SDF | Download SDF |
PubChem ID | 54698642 | Appearance | Powder |
Formula | C21H21ClFN5O4 | M.Wt | 461.9 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | Soluble in DMSO > 10 mM | ||
Chemical Name | (6S)-2-[(3-chloro-4-fluorophenyl)methyl]-8-ethyl-10-hydroxy-N,6-dimethyl-1,9-dioxo-6,7-dihydropyrazino[5,6]pyrrolo[1,3-b]pyridazine-4-carboxamide | ||
SMILES | CCN1CC(N2C3=C(C(=C2C1=O)O)C(=O)N(N=C3C(=O)NC)CC4=CC(=C(C=C4)F)Cl)C | ||
Standard InChIKey | JSRREMIKIHJGAA-JTQLQIEISA-N | ||
Standard InChI | InChI=1S/C21H21ClFN5O4/c1-4-26-8-10(2)28-16-14(18(29)17(28)21(26)32)20(31)27(25-15(16)19(30)24-3)9-11-5-6-13(23)12(22)7-11/h5-7,10,29H,4,8-9H2,1-3H3,(H,24,30)/t10-/m0/s1 | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | MK-2048 is a second generation inhibitor of HIV-1 integrase with IC50 values of 0.075 μM and 0.08 μM for subtype B and subtype C integrase, respectively. | |||||
Targets | subtype B integrase | subtype C integrase | ||||
IC50 | 0.075 μM | 0.08 μM |
MK-2048 Dilution Calculator
MK-2048 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.165 mL | 10.8249 mL | 21.6497 mL | 43.2994 mL | 54.1243 mL |
5 mM | 0.433 mL | 2.165 mL | 4.3299 mL | 8.6599 mL | 10.8249 mL |
10 mM | 0.2165 mL | 1.0825 mL | 2.165 mL | 4.3299 mL | 5.4124 mL |
50 mM | 0.0433 mL | 0.2165 mL | 0.433 mL | 0.866 mL | 1.0825 mL |
100 mM | 0.0216 mL | 0.1082 mL | 0.2165 mL | 0.433 mL | 0.5412 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
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MK-2048 is a second generation inhibitor of HIV-1 integrase with IC50 values of 0.075 μM and 0.08 μM for subtype B and subtype C integrase, respectively.
Integration of viral cDNA into the host genome is one of the definitive features of retrovirus replication. Integrase inhibitors are active against both B and non-B subtypes in therapy. Subtype C variants are responsible for approximately 50% of infections worldwide, mostly in Sub-Saharan Africa and India. After viral entry and reverse transcription, reverse-transcribed double-stranded blunt-ended DNA is incorporated into the host cell genome through two catalytic activities mediated by integrase. MK-2048 could inhibit the strand transfer process catalyzed by integrase.
The inhibition activity of MK-2048 against integrase was evaluated by means of purified recombinant subtype B and C integrase enzymes, which were obtained and amplified from viruses in long-term infected patients. Purified recombinant subtype B and C integrase enzymes were incubated with increasing concentrations of MK-2048 and corresponding templates. MK-2048 possesses inhibition activities for strand transfer against subtype B and C enzymes, whose IC50 values were 0.075 μM and 0.08 μM, respectively. Disintegration was inhibited by high concentrations of MK-2048 to a comparable extent with both subtype B and C enzymes.
Inhibition of replication by MK-2048 was also evaluated in cell culture based assays using cord blood mononuclear cells. EC50 for subtype B viruses varies from 0.0003 μM to 0.0148 μM and 0.0007 μM to 0.0033 μM for subtype C viruses.
References:
1.Bar-Magen T, Sloan R D, Faltenbacher V H, et al. Comparative biochemical analysis of HIV-1 subtype B and C integrase enzymes[J]. Retrovirology, 2009, 6(1): 103.
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Identification of novel mutations responsible for resistance to MK-2048, a second-generation HIV-1 integrase inhibitor.[Pubmed:20610719]
J Virol. 2010 Sep;84(18):9210-6.
MK-2048 represents a prototype second-generation integrase strand transfer inhibitor (INSTI) developed with the goal of retaining activity against viruses containing mutations associated with resistance to first-generation INSTIs, raltegravir (RAL) and elvitegravir (EVG). Here, we report the identification of mutations (G118R and E138K) which confer resistance to MK-2048 and not to RAL or EVG. These mutations were selected in vitro and confirmed by site-specific mutagenesis. G118R, which appeared first in cell culture, conferred low levels of resistance to MK-2048. G118R also reduced viral replication capacity to approximately 1% that of the isogenic wild-type (wt) virus. The subsequent selection of E138K partially restored replication capacity to approximately 13% of wt levels and increased resistance to MK-2048 to approximately 8-fold. Viruses containing G118R and E138K remained largely susceptible to both RAL and EVG, suggesting a unique interaction between this second-generation INSTI and the enzyme may be defined by these residues as a potential basis for the increased intrinsic affinity and longer "off" rate of MK-2048. In silico structural analysis suggests that the introduction of a positively charged arginine at position 118, near the catalytic amino acid 116, might decrease Mg(2+) binding, compromising enzyme function and thus leading to the significant reduction in both integration and viral replication capacity observed with these mutations.