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| Targets |
HIV-1 integrase inhibitor 8 targets HIV-1 integrase, a viral enzyme responsible for integrating viral DNA into the host cell genome. Integration is an essential step in the HIV replication cycle. The compound inhibits both the 3′-processing (TC) and strand-transfer (ST) activities of the enzyme. In the presence of Mn2+ as the cationic cofactor, HIV-1 integrase inhibitor 8 has IC50 values of 275 μM for 3′-processing and 200 μM for strand-transfer activities. By inhibiting integrase, the compound prevents viral DNA integration and blocks HIV replication.
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| ln Vitro |
By using a gel assay, HIV-1 integrase inhibitor 8 has IC50 values of 275 µM and 200 µM for 3′-processing (TC) and strand-transfer (ST) activities in the presence of Mn2+ as the cationic cofactor, respectively. With an IC50 value of 200 µM, it inhibits the strand-transfer (ST) activity[1]. Gel electrophoresis is used to track the DNA relaxing activity of MCV topoisomerase, whilst a microtiter assay was used to track the DNA cleavage and religation activities. HIV-1 integrase inhibitor 8 has IC50 values of 500 µM and 200 µM, respectively, for inhibiting MCV topoisomerase and DNA religation. This finding shows that compound 8 is not effective against topoisomerase in any of the two assays[1]. In HeLa cells, HIV-1 integrase inhibitor 8 causes cytotoxicity and has an LD50 (dosage at which cell death reduces the signal by50%) of 20 μM[1].
HIV-1 integrase inhibitor 8 has been tested in vitro against the 3′-processing (TC) and strand-transfer (ST) activities of HIV-1 integrase using a gel-based assay. In the presence of Mn2+ as the cationic cofactor, the compound has IC50 values of 275 μM for 3′-processing and 200 μM for strand-transfer activities. The compound also inhibits MCV topoisomerase and DNA religation with IC50 values of 500 μM and 200 μM, respectively. These findings indicate that the compound is not effective against topoisomerase in either assay. In HeLa cells, the compound causes cytotoxicity with an LD50 of 20 μM. |
| ln Vivo |
In vivo activity data for HIV-1 integrase inhibitor 8 are not extensively documented in the available literature. The compound has been studied primarily in vitro for its effects on HIV-1 integrase activity. In HeLa cells, the compound causes cytotoxicity with an LD50 of 20 μM, suggesting potential toxicity concerns. Further in vivo studies, including efficacy in animal models of HIV infection, would be required to fully characterize the compound's therapeutic potential. The compound serves as a research tool for studying HIV-1 integrase inhibition and viral replication mechanisms.
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| Enzyme Assay |
The in vitro enzyme assay for HIV-1 integrase inhibitor 8 involves measuring its inhibition of HIV-1 integrase enzymatic activity. The assay uses a gel-based method to assess the 3′-processing (TC) and strand-transfer (ST) activities of the enzyme. Recombinant HIV-1 integrase is incubated with a DNA substrate representing the viral DNA ends. The reaction is carried out in the presence of Mn2+ as the cationic cofactor. HIV-1 integrase inhibitor 8 is added at various concentrations. The products of the 3′-processing and strand-transfer reactions are separated by gel electrophoresis and quantified. IC50 values are determined by fitting the inhibition data to a dose-response curve.
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| Cell Assay |
In vitro cellular assays for HIV-1 integrase inhibitor 8 typically use HeLa cells to assess cytotoxicity. Cells are treated with the compound at various concentrations for a defined period. Cell viability is measured using standard assays such as MTT, CellTiter-Glo, or trypan blue exclusion. The compound's cytotoxicity is quantified as the LD50 (lethal dose 50%). Additionally, HIV-1 replication assays in infected cell lines could be used to assess antiviral activity. These assays confirm the compound's cellular effects and support its use in HIV research.
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| Animal Protocol |
In vivo animal experiments for HIV-1 integrase inhibitor 8 are not extensively documented. As a research compound studied primarily in vitro, HIV-1 integrase inhibitor 8 has not been widely tested in animal models. Standard in vivo efficacy studies would involve mouse models of HIV infection, where the compound would be administered via oral or parenteral routes. Viral load and immune cell populations would be measured to assess antiviral efficacy. Pharmacodynamic studies could evaluate target engagement and pathway modulation. Further studies are needed to characterize its in vivo activity.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of HIV-1 integrase inhibitor 8 are not extensively documented. As a small molecule with a molecular weight of 308.41, the compound is expected to have reasonable bioavailability. Its spirobi[indene] structure may influence its absorption, distribution, metabolism, and excretion (ADME) properties. The compound's cytotoxicity in HeLa cells (LD50 of 20 μM) suggests that careful dose optimization would be required for in vivo studies. Further pharmacokinetic studies are necessary to fully characterize its PK profile.
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| Toxicity/Toxicokinetics |
Toxicological data for HIV-1 integrase inhibitor 8 are limited. The compound causes cytotoxicity in HeLa cells with an LD50 of 20 μM, indicating potential toxicity concerns. As a research compound, HIV-1 integrase inhibitor 8 has not undergone extensive toxicological evaluation. Standard cytotoxicity assays in cell lines are typically performed to assess safety margins. Further preclinical toxicology studies would be required to assess safety, determine no-observed-adverse-effect levels (NOAEL), and evaluate potential off-target effects before clinical development.
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| References | |
| Additional Infomation |
HIV-1 integrase inhibitor 8 targets HIV-1 integrase, inhibiting 3′-processing (TC) and strand-transfer (ST) activities. In the presence of Mn2+, it has IC50 values of 275 μM for 3′-processing and 200 μM for strand-transfer. The compound causes cytotoxicity in HeLa cells with an LD50 of 20 μM. It has a molecular weight of 308.41 and formula C21H24O2. The compound is used as a research tool for studying HIV-1 integrase inhibition. No clinical trials or regulatory approvals have been reported.
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| Molecular Formula |
C21H24O2
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| Molecular Weight |
308.41
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| Exact Mass |
308.178
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| CAS # |
1568-80-5
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| PubChem CID |
74071
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| Appearance |
White to off-white solid powder
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| Density |
1.21±0.1 g/cm3(Predicted)
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| Boiling Point |
478.5℃ at 760 mmHg
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| Melting Point |
213-214 °C
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| Flash Point |
220.4℃
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| Vapour Pressure |
8.84E-10mmHg at 25°C
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| LogP |
4.746
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
23
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| Complexity |
436
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1(CC2(CC(C3=C2C=C(C=C3)O)(C)C)C4=C1C=CC(=C4)O)C
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| InChi Key |
SICLLPHPVFCNTJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H24O2/c1-19(2)11-21(17-9-13(22)5-7-15(17)19)12-20(3,4)16-8-6-14(23)10-18(16)21/h5-10,22-23H,11-12H2,1-4H3
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| Chemical Name |
1,1,1',1'-tetramethyl-3,3'-spirobi[2H-indene]-5,5'-diol
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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: 125 mg/mL (405.30 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.74 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 20.8 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: ≥ 2.08 mg/mL (6.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 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: ≥ 2.08 mg/mL (6.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2424 mL | 16.2122 mL | 32.4244 mL | |
| 5 mM | 0.6485 mL | 3.2424 mL | 6.4849 mL | |
| 10 mM | 0.3242 mL | 1.6212 mL | 3.2424 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.
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