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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Purity: ≥98%
Bevirimat (formerly known as PA-457, MPC-4326 and YK FH312), an analog of betulinic acid, is a novel and potent anti-HIV drug that acts as a maturation inhibitor. Existing antiretroviral treatments for HIV type-1 (HIV-1) disease are limited by problems of resistance and drug-drug interactions. Bevirimat has a mechanism of action that is distinct from other antiretroviral agents. Specific inhibition of the final rate-limiting step in Gag processing by bevirimat prevents release of mature capsid protein from its precursor (CA-SP1), resulting in the production of immature, non-infectious virus particles. Bevirimat inhibits replication of both wild-type and drug-resistant HIV-1 isolates in vitro, achieving similar 50% inhibitory concentration values with both categories. Serial drug passage studies have identified six single amino acid substitutions that independently confer bevirimat resistance. These resistance mutations occur at or near the CA-SP1 cleavage site, which is not a known target for resistance to other antiretroviral drugs. Bevirimat has demonstrated a consistent pharmacokinetic profile in healthy volunteers and HIV-infected patients, with peak plasma concentrations attained approximately 1-3 h after dosing. Plasma concentrations decrease in a log-linear manner with a mean plasma elimination halflife of 58-80 h, supporting once-daily dosing. Animal studies suggest that elimination of bevirimat is primarily by hepatic glucuronidation and hepatobiliary excretion. There is minimal renal elimination, with < 1% of the administered dose appearing in the urine. In responsive patients, bevirimat has demonstrated a robust dosedependent reduction in viral load (> 1.5 log10 copies/ml). Short-term administration (< or = 14 days) of bevirimat is well tolerated, even when used in combination with other antiretroviral agents. Further studies to evaluate the long-term efficacy and tolerability of bevirimat are currently underway.
References |
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Molecular Formula |
C36H56O6
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Molecular Weight |
584.8263
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Exact Mass |
584.41
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Elemental Analysis |
C, 73.93; H, 9.65; O, 16.41
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CAS # |
174022-42-5
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Appearance |
Solid powder
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SMILES |
CC1(C)[C@@H](OC(CC(C)(C(O)=O)C)=O)CC[C@]2(C)[C@@]3([H])CC[C@]4([H])[C@@]5([H])[C@H](C(C)=C)CC[C@@](C(O)=O)5CC[C@](C)4[C@@](C)3CC[C@@]12[H]
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InChi Key |
YJEJKUQEXFSVCJ-WRFMNRASSA-N
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InChi Code |
InChI=1S/C36H56O6/c1-21(2)22-12-17-36(30(40)41)19-18-34(8)23(28(22)36)10-11-25-33(7)15-14-26(42-27(37)20-31(3,4)29(38)39)32(5,6)24(33)13-16-35(25,34)9/h22-26,28H,1,10-20H2,2-9H3,(H,38,39)(H,40,41)/t22-,23+,24-,25+,26-,28+,33-,34+,35+,36-/m0/s1
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Chemical Name |
(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-((3-carboxy-3-methylbutanoyl)oxy)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-3aH-cyclopenta[a]chrysene-3a-carboxylic acid
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Synonyms |
YK FH312; YK FH-312; YK FH 312; MPC4326; MPC 4326; MPC-4326; PA457; PA 457; PA-457; FH11327; FH-11327; FH 11327; YK FH312
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO : 50~100 mg/mL ( 85.49 ~170.98 mM)
Ethanol : ~20 mg/mL |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.27 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (4.27 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.27 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (4.27 mM) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.7099 mL | 8.5495 mL | 17.0990 mL | |
5 mM | 0.3420 mL | 1.7099 mL | 3.4198 mL | |
10 mM | 0.1710 mL | 0.8549 mL | 1.7099 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Mean reduction in viral load following bevirimat treatment by dose.[1].Antimicrob Agents Chemother. 2007 Oct;51(10):3574-81. td> |
Pharmacokinetic/pharmacodynamic model for single-dose bevirimat. [1].Antimicrob Agents Chemother. 2007 Oct;51(10):3574-81. td> |
Goodness of fit of the pharmacokinetic (above) and pharmacodynamic (below) models for all bevirimat (PA-457) concentration and viral load data. [1].Antimicrob Agents Chemother. 2007 Oct;51(10):3574-81. td> |
Mean concentration-time pharmacokinetic profiles for 75, 150, and 250 mg of bevirimat (PA-457) administered as a single oral dose to HIV-infected patients. [1].Antimicrob Agents Chemother. 2007 Oct;51(10):3574-81. td> |
Example fit of the pharmacokinetic (above) and pharmacodynamic (below) model in a typical subject. [1].Antimicrob Agents Chemother. 2007 Oct;51(10):3574-81. td> |