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| Targets |
HIV-1
Reverse transcriptase-IN-1 targets the HIV-1 reverse transcriptase enzyme. As a non-nucleoside reverse transcriptase inhibitor (NNRTI), it binds to an allosteric site on the enzyme, inducing a conformational change that inhibits its polymerase activity. This prevents the reverse transcription of viral RNA into DNA, a critical step in the HIV replication cycle. It is a diarylbenzopyrimidine (DABP) analogue. |
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| ln Vitro |
In vitro, Reverse transcriptase-IN-1 is a potent inhibitor of HIV-1 reverse transcriptase with an IC50 of 13.7 nM. It also shows activity against HIV-1 IIIB, E138K, and K103N mutants with IC50 values of 4.3 nM and 3.6 nM, respectively. Its activity is assessed in reverse transcriptase inhibition assays and in cell-based assays measuring HIV-1 replication.
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| ln Vivo |
Reverse transcriptase-IN-1 (Compound 12z) has a markedly increased oral bioavailability of 16.5% in rats when administered at a dose of 5 mg/kg. Reverse transcriptase-IN-1 has an inherent microsome clearance of 33.2 μL/min/mg proteins in rats. Reverse transcriptase-IN-1 is absorbed at two different doses, with mean residence times (MRTs) of 11.8 hours (5 mg/kg, po) and 11.4 hours (1 mg/kg, iv), according to the PK study and safety evaluation. At a dose of 5 mg/kg, the Cmax of reverse transcriptase-IN-1 is 39.9 ng/mL. Rats used in a single-dose toxicity test for reverse transcriptase-IN-1 exhibit no signs of death, and the animals' body weight did not drop abnormally in the week after an intragastrical dose of 293 mg/kg body weight. According to the aforementioned findings, reverse transcriptase-IN-1 may be a viable oral bioavailable option for studying HIV-1 infection in humans[1].
In vivo, Reverse transcriptase-IN-1 is orally active. Its potential for in vivo applications in the treatment of HIV-1 infection is suggested by its potent in vitro activity and oral bioavailability. Studies in appropriate animal models would be needed to evaluate its in vivo efficacy, pharmacokinetics, and safety profile. |
| Enzyme Assay |
For non-cellular enzyme/receptor binding studies, Reverse transcriptase-IN-1's activity is evaluated in HIV-1 reverse transcriptase enzyme inhibition assays. Purified HIV-1 RT is incubated with a substrate and varying concentrations of the compound. Enzyme activity is measured, and IC50 values are calculated from the dose-response curves.
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| Cell Assay |
For in vitro cellular experiments, HIV-1 infected cells are cultured and treated with Reverse transcriptase-IN-1 at various concentrations. Viral replication is assessed by measuring the production of viral proteins or the amount of viral RNA in the culture supernatant. The compound's ability to inhibit HIV-1 replication is confirmed by its potent activity against both wild-type and mutant strains.
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| Animal Protocol |
In vivo animal studies for Reverse transcriptase-IN-1 are not extensively detailed in the provided literature. As an orally active compound, it would be evaluated in animal models of HIV-1 infection. The compound would be administered orally, and its efficacy would be assessed by measuring viral load.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Reverse transcriptase-IN-1 are not extensively detailed in the provided sources. It has a molecular weight of 447.45 and a purity of 99%. It is a small molecule with potential for oral bioavailability. Comprehensive pharmacokinetic studies are needed to fully characterize its absorption, distribution, metabolism, and excretion profile.
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| Toxicity/Toxicokinetics |
The toxicity profile of Reverse transcriptase-IN-1 is not explicitly detailed in the provided sources. As a research compound, standard laboratory safety precautions should be followed when handling it. It is intended for research use only and is not for human therapeutic applications. Its safety would be evaluated in the context of its development as an antiviral agent.
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| References |
[1]. Han S, et al. Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles. ACS Infect Dis. 2019 Oct 24.
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| Additional Infomation |
Reverse transcriptase-IN-1 is a potent, orally active HIV-1 non-nucleoside reverse transcriptase inhibitor with a molecular formula of C25H17N7O2 and a molecular weight of 447.45. It has an IC50 of 13.7 nM against HIV-1 reverse transcriptase. This research compound is for laboratory use only and has not been approved for clinical applications.
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| Molecular Formula |
C25H17N7O2
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|---|---|
| Molecular Weight |
447.45
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| Exact Mass |
447.144
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| CAS # |
2380001-43-2
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| PubChem CID |
139600333
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
708.3±70.0 °C at 760 mmHg
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| Flash Point |
382.1±35.7 °C
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| Vapour Pressure |
0.0±2.3 mmHg at 25°C
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| Index of Refraction |
1.729
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| LogP |
4.56
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
34
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| Complexity |
831
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(=C(NC2=NC(NC3C=CC(=CC=3)C#N)=NC3C2=CC=CC=3)C(C)=CC(=C1)/C=C/C#N)[N+]([O-])=O
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| InChi Key |
MNZKGXAFXCQSCG-SNAWJCMRSA-N
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| InChi Code |
InChI=1S/C25H17N7O2/c1-16-13-18(5-4-12-26)14-22(32(33)34)23(16)30-24-20-6-2-3-7-21(20)29-25(31-24)28-19-10-8-17(15-27)9-11-19/h2-11,13-14H,1H3,(H2,28,29,30,31)/b5-4+
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| Chemical Name |
4-[[4-[4-[(E)-2-cyanoethenyl]-2-methyl-6-nitroanilino]quinazolin-2-yl]amino]benzonitrile
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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 : 12.5 mg/mL (27.94 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.79 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 12.5 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: 1.25 mg/mL (2.79 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 ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2349 mL | 11.1744 mL | 22.3489 mL | |
| 5 mM | 0.4470 mL | 2.2349 mL | 4.4698 mL | |
| 10 mM | 0.2235 mL | 1.1174 mL | 2.2349 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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