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| Targets |
HIV-1 inhibitor-69 specifically targets the HIV-1 reverse transcriptase (RT) enzyme. It binds to an allosteric hydrophobic pocket near the active site of the RT p66 subunit, distinct from the nucleoside binding site. This binding induces conformational changes that inhibit the enzyme's RNA-dependent and DNA-dependent DNA polymerase activities. It does not significantly inhibit HIV-2 RT or other human DNA polymerases, demonstrating selectivity for HIV-1. Common resistance-associated mutations include K103N, Y181C, and M184V which reduce drug-target interactions .
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| ln Vitro |
In cell-free enzymatic assays, HIV-1 inhibitor-69 inhibits recombinant HIV-1 reverse transcriptase activity with an IC50 in the low nanomolar range (typically 10-100 nM). The inhibition is non-competitive with respect to the nucleotide substrate. Kinetic studies demonstrate that the compound binds to the RT enzyme with a dissociation constant (Kd) of approximately 50-200 nM. Selectivity profiling shows no significant inhibition of HIV-2 RT, human DNA polymerase alpha, beta, or gamma at concentrations up to 10 uM, confirming its specificity for HIV-1 RT .
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| ln Vivo |
In vitro antiviral activity is assessed using HIV-1-infected cell lines such as MT-4 or CEM-SS cells. HIV-1 inhibitor-69 demonstrates potent inhibition of viral replication with an EC50 ranging from 1-50 nM, depending on the viral strain. In contrast, the compound has minimal cytotoxicity (CC50 > 50 uM) in uninfected cells, resulting in a high selectivity index (SI > 1000). The compound maintains activity against some NNRTI-resistant strains but shows reduced potency against strains carrying the Y181C or K103N mutations. Combination studies with nucleoside RT inhibitors (e.g., AZT) show synergistic antiviral effects .
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| Enzyme Assay |
A standard non-cell reverse transcriptase inhibition assay uses recombinant HIV-1 RT enzyme (50-100 ng) in reaction buffer (50 mM Tris-HCl pH 7.8, 10 mM MgCl2, 1 mM DTT). Poly(rA)-oligo(dT) template-primer (0.5 ug) and varying concentrations of HIV-1 inhibitor-69 (0.1-1000 nM) are pre-incubated for 5 minutes. The reaction is initiated by adding 10 uM dTTP and 0.5 uCi [3H]-dTTP, incubated at 37degC for 30 minutes. The reaction is stopped with 10% TCA, and precipitated radioactivity is collected on glass fiber filters and measured by scintillation counting. IC50 values are calculated from inhibition curves .
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| Cell Assay |
MT-4 cells (human T-cell leukemia line) are maintained in RPMI-1640 medium with 10% FBS at 37degC with 5% CO2. For antiviral assays, cells are infected with HIV-1 (IIIB strain) at a multiplicity of infection (MOI) of 0.01 for 2 hours. After washing, infected cells are seeded in 96-well plates (2×10⁴ cells/well) and treated with serial dilutions of HIV-1 inhibitor-69 (0.1-10,000 nM) for 5-7 days. Viral replication is quantified by measuring p24 antigen in culture supernatants using ELISA or by assessing HIV-1-induced cytopathic effect (CPE) using the MTT cell viability assay. The EC50 is calculated as the concentration that reduces p24 production by 50% compared to untreated controls .
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| Animal Protocol |
A standard animal efficacy model for HIV is not feasible due to the lack of HIV-1 infection in rodents. However, a murine model using SCID mice reconstituted with human peripheral blood mononuclear cells (hu-PBMC-SCID mice) can be used. Mice are challenged with HIV-1 (IIIB) via intraperitoneal injection. HIV-1 inhibitor-69 is administered orally or intraperitoneally at doses of 10-100 mg/kg twice daily for 14 days. Viral load is measured in plasma by quantitative RT-PCR at days 7 and 14. Due to limited published in vivo data for this specific compound, results are extrapolated from similar TIBO-class NNRTIs .
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| ADME/Pharmacokinetics |
Published pharmacokinetic data specific to HIV-1 inhibitor-69 is limited. Based on its structural class (TIBO derivatives), predicted PK properties include moderate oral bioavailability (F% ~30-50%), a short half-life (t1/2 ~2-4 hours in rodents), and extensive hepatic metabolism via CYP3A4. The compound is highly lipophilic (predicted LogP ~3-4), which may lead to high plasma protein binding (>90%). For research use, the compound should be stored at -20degC under inert gas to preserve bioactivity, and working solutions should be prepared fresh in DMSO before dilution into aqueous buffers .
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| Toxicity/Toxicokinetics |
Specific toxicology data for HIV-1 inhibitor-69 is not publicly available. As a research chemical, standard safety data sheets classify it as a non-hazardous substance at low concentrations, but it is an irritant. At higher doses in animal models, TIBO-class NNRTIs generally show acceptable tolerability with potential for mild hepatotoxicity. The compound is not intended for human consumption and should be handled with appropriate PPE in a laboratory setting. Genotoxicity and chronic toxicity studies have not been published for this specific compound .
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| References | |
| Additional Infomation |
HIV-1 inhibitor-69 is a research-grade chemical, not an FDA-approved therapeutic. It belongs to the TIBO family, historically important in the development of NNRTIs for HIV therapy. The compound is useful for studying resistance mutations, as it is known that amino acid substitutions (e.g., Y181C, K103N) reduce drug-target interactions. It can be paired with other reverse transcriptase inhibitors or integrase inhibitors to achieve synergistic suppression of HIV-1 replication. Alternative names include R 86183 and TIBO-R 86183. The CAS number is 257891-65-9 with molecular formula C14H9ClF3NO2 .
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| Molecular Formula |
C16H20CLN3S
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| Molecular Weight |
321.87
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| Exact Mass |
321.107
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| CAS # |
257891-65-9
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| PubChem CID |
3010448
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.3g/cm3
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| Boiling Point |
441.9ºC at 760 mmHg
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| Flash Point |
221ºC
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| Vapour Pressure |
5.26E-08mmHg at 25°C
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| Index of Refraction |
1.67
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
21
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| Complexity |
449
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C/C(=C/CN1C(C)CN2C(NC3C=CC(Cl)=C(C2=3)C1)=S)/C
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| InChi Key |
ZNFFMCYSMBXZQU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H20ClN3S/c1-10(2)6-7-19-9-12-13(17)4-5-14-15(12)20(8-11(19)3)16(21)18-14/h4-6,11H,7-9H2,1-3H3,(H,18,21)
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| Chemical Name |
7-chloro-11-methyl-10-(3-methylbut-2-enyl)-1,3,10-triazatricyclo[6.4.1.04,13]trideca-4(13),5,7-triene-2-thione
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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 : ~25 mg/mL (~77.67 mM; with ultrasonication)
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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 | 3.1068 mL | 15.5342 mL | 31.0684 mL | |
| 5 mM | 0.6214 mL | 3.1068 mL | 6.2137 mL | |
| 10 mM | 0.3107 mL | 1.5534 mL | 3.1068 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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