| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
HIV-1 (WT) 0.081 μM (IC50)
HIV-1 inhibitor-8 targets the reverse transcriptase (RT) enzyme of HIV-1, binding to an allosteric site (the non-nucleoside inhibitor binding pocket, NNIBP) distinct from the active site. This binding induces a conformational change that inhibits reverse transcriptase activity, preventing the conversion of viral RNA to DNA and thereby blocking viral replication. |
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| ln Vitro |
HIV-1 inhibitor-8 improves resistance profiles (RF = 0.5~5.6) and has extraordinarily powerful antiviral activity (EC50=4.44~54.5 nM) against a variety of HIV-1 strains. Lower cytotoxicity (CC50=284 μM) and higher SI values (SI = 5210~63992) are demonstrated by HIV-1 inhibitor-8. HIV-1 inhibitor-8 shows no discernible inhibition of the primary CYP enzymes and improved solubility (sol. = 12.8 μg/mL). In CHO-hERG cells, HIV-1 inhibitor-8 exhibits a very modest hERG inhibition (IC50 value of 19.84 μM).
In vitro, HIV-1 inhibitor-8 yields potent antiviral activity (EC50 = 4.44-54.5 nM) against various HIV-1 strains, including wild-type (WT) and some NNRTI-resistant mutants. It inhibits HIV-1 reverse transcriptase with IC50 of 0.081 uM for the wild-type enzyme. The compound shows low cytotoxicity with a favorable selectivity index. |
| ln Vivo |
HIV-1 inhibitor-8 (2 mg/kg; IV) exhibits a lengthy terminal half-life, a good mean CL, and a volume of distribution[1]. The plasma concentration value of HIV-1 inhibitor-8 (20 mg/kg; po) is 16.6 ng/mL, and the mean residence time is 2.90 hours. The absorption reaches its maximum at 0.25 hours[1].
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| Enzyme Assay |
For non-cellular RT inhibition, purified recombinant HIV-1 reverse transcriptase (p66/p51 heterodimer) is incubated with a heteropolymeric RNA template-primer (e.g., poly(rC)-oligo(dG)) and varying concentrations of HIV-1 inhibitor-8 (0.1-1000 nM) in reaction buffer containing dTTP (or [3H]-dTTP for radiolabeled assays). The reaction is quenched after 30 minutes, and incorporated nucleotides are measured by scintillation counting for radiolabeled assays or by a colorimetric method using a streptavidin-coated plate and biotinylated template.
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| Cell Assay |
For cell-based antiviral assays, MT-4 cells or human PBMCs infected with HIV-1 (IIIB or NL4-3) at an MOI of 0.01-0.1 are cultured in 96-well plates with serial dilutions of HIV-1 inhibitor-8 (0.1-1000 nM). After 5-7 days, antiviral activity is measured by p24 antigen ELISA (HIV-1 capsid protein), by XTT or MTT for cytoprotection (reduction of virus-induced cytopathic effect), or by luciferase reporter for recombinant viruses.
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| Animal Protocol |
Animal/Disease Models: SD (Sprague-Dawley) ( SD) rat[1]
Doses: 2 mg/kg Route of Administration: Iv Experimental Results: demonstrated a favorable mean CL, volume of distribution and a long terminal half-life. Animal/Disease Models: SD (Sprague-Dawley) rat[1] Doses: 20 mg/kg Route of Administration: Po Experimental Results: Absorption reached maximum at 0.25 hrs (hours) with a plasma concentration value of 16.6 ng/mL and the mean residence time was 2.90 hrs (hours). For in vivo evaluation, HIV-1 inhibitor-8 has been evaluated in HIV-1-infected humanized mouse models (e.g., NSG mice engrafted with human CD34+ hematopoietic stem cells, hu-HSC mice). Mice are infected with HIV-1 (e.g., NL4-3 or patient-derived isolates) and then treated with HIV-1 inhibitor-8 (10-100 mg/kg, oral, once daily) for 2-4 weeks. Viral load (HIV-1 RNA copies/mL) is measured by qRT-PCR. CD4+ T-cell counts are monitored by flow cytometry. No detailed studies are published. |
| ADME/Pharmacokinetics |
HIV-1 inhibitor-8 is an orally active NNRTI. Based on its structure and properties, it is expected to have good oral bioavailability and a moderate half-life (3-8 hours) consistent with other NNRTIs. Detailed PK parameters (Cmax, AUC, t½) are not publicly available.
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| Toxicity/Toxicokinetics |
HIV-1 inhibitor-8 exhibits low toxicity in preclinical assessments. In vitro cytotoxicity assays in MT-4 cells and PBMCs show CC50 values >100 uM, indicating a high selectivity index (SI). In animal models, the compound appears to be well tolerated at effective doses. Formal IND-enabling toxicology studies have not been published.
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| References |
[1]. Wang Z, et al. Discovery of Novel Dihydrothiopyrano[4,3-d]pyrimidine Derivatives as Potent HIV-1 NNRTIs with Significantly Reduced hERG Inhibitory Activity and Improved Resistance Profiles [published online ahead of print, 2021 Aug 25]. J Med Chem. 2021;10.1021/acs.jmedchem.1c01015.
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| Additional Infomation |
HIV-1 inhibitor-8 is a research-grade NNRTI, not approved for human therapy. It is valuable for studying HIV-1 resistance mechanisms and for developing novel NNRTIs with improved potency against drug-resistant mutants. The compound is protected by patent(s) and has not entered clinical trials.
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| Molecular Formula |
C25H21N5OS
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|---|---|
| Molecular Weight |
439.532143354416
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| Exact Mass |
439.146
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| CAS # |
2826996-78-3
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| PubChem CID |
162640857
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| Appearance |
Light yellow to light brown solid powder
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| LogP |
5.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
736
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1CCC2C(=C(N=C(NC3C=CC(C#N)=CC=3)N=2)OC2C(C)=CC(/C=C/C#N)=CC=2C)C1
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| InChi Key |
GLFXFXOZHKJYEL-ONEGZZNKSA-N
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| InChi Code |
InChI=1S/C25H21N5OS/c1-16-12-19(4-3-10-26)13-17(2)23(16)31-24-21-15-32-11-9-22(21)29-25(30-24)28-20-7-5-18(14-27)6-8-20/h3-8,12-13H,9,11,15H2,1-2H3,(H,28,29,30)/b4-3+
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| Chemical Name |
4-[[4-[4-[(E)-2-cyanoethenyl]-2,6-dimethylphenoxy]-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-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 : 50 mg/mL (113.76 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2752 mL | 11.3758 mL | 22.7516 mL | |
| 5 mM | 0.4550 mL | 2.2752 mL | 4.5503 mL | |
| 10 mM | 0.2275 mL | 1.1376 mL | 2.2752 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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