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| Targets |
The primary target of DPC 681 is the HIV-1 protease, a homodimeric aspartyl protease. This enzyme is critical for the HIV life cycle. During viral assembly, the Gag and Gag-Pol polyproteins are translated and transported to the cell membrane. For the virus to become infectious, HIV protease must cleave these polyproteins at specific sites to release individual functional proteins, including the structural proteins (matrix, capsid, nucleocapsid) and the enzymes (protease, reverse transcriptase, integrase) needed for the next round of infection. By binding to the active site of the HIV protease and inhibiting its catalytic activity, DPC 681 prevents this crucial maturation step, leading to the production of non-infectious viral particles. The target is the same for both wild-type and mutant HIV strains.
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| ln Vitro |
DPC 681 demonstrates exceptional potency and selectivity in vitro as an inhibitor of HIV-1 protease. Its activity is typically reported as an IC₉₀, the concentration required to inhibit 90% of viral replication, which is 4 to 40 nM for wild-type HIV-1. This indicates that it is a highly potent antiviral agent. A key feature of DPC 681 is its activity against clinically relevant mutant variants of HIV. This is a significant advantage, as drug resistance is a major challenge in HIV therapy. The compound's ability to inhibit these resistant mutants suggests it may have a different binding mode or a higher binding affinity that allows it to maintain efficacy despite mutations in the protease active site. Its selectivity for the viral protease over human proteases is crucial for its safety.
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| ln Vivo |
While specific in vivo data for DPC 681 is not detailed in the provided search results, its design as a potent inhibitor targeting a critical viral enzyme suggests it would have significant antiviral activity in vivo. In animal models of HIV infection, such as humanized mouse models or simian immunodeficiency virus (SIV) models, an inhibitor like DPC 681 would be expected to reduce viral load. Its ability to inhibit clinically relevant mutants suggests it could be effective against drug-resistant HIV strains in vivo. The compound's pharmacokinetic properties, including its bioavailability and half-life, would determine its efficacy and dosing regimen.
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| Enzyme Assay |
The in vitro enzyme assay for DPC 681 measures its ability to inhibit the catalytic activity of HIV-1 protease. In this assay, purified recombinant HIV-1 protease is incubated with a fluorogenic or chromogenic peptide substrate that mimics the viral polyprotein cleavage site. Cleavage of the substrate by the active protease releases a detectable signal. The assay is performed in the presence of varying concentrations of DPC 681, and the enzyme activity is measured by monitoring the rate of signal generation. A control without the inhibitor defines 100% enzyme activity. The concentration of the compound required to inhibit 90% of the enzyme activity (IC₉₀) is then determined from the dose-response curve.
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| Cell Assay |
In vitro cell-based assays for DPC 681 evaluate its antiviral activity in HIV-infected cells. In a typical assay, human T-cell lines (such as MT-4 or CEM cells) are infected with HIV-1 at a defined multiplicity of infection. The infected cells are then cultured in the presence of varying concentrations of DPC 681. After several days of incubation, the extent of viral replication is measured. This is typically done by quantifying the amount of viral p24 antigen in the cell culture supernatant using an ELISA, or by measuring the cytopathic effect (CPE) of the virus on the cells using a dye-based viability assay. The IC₉₀ value, the concentration required to inhibit 90% of viral replication, is then calculated. These assays confirm the compound's antiviral activity in a cellular context.
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| Animal Protocol |
In vivo animal studies for HIV protease inhibitors are often conducted in specialized models, as HIV does not naturally infect standard laboratory animals. Typically, severe combined immunodeficient (SCID) mice engrafted with human peripheral blood mononuclear cells (hu-PBL-SCID) or human hematopoietic stem cells (hu-HSC-SCID) are used. These humanized mice can be infected with HIV-1. In such a model, DPC 681 would be administered orally or via injection to evaluate its ability to suppress viral replication, as measured by plasma viral RNA levels and the preservation of CD4+ T cells. These studies are crucial for assessing in vivo efficacy and for guiding dose selection for clinical trials.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) data for DPC 681 is not extensively reported in the provided search results. However, as a small molecule with a molecular weight of 669.85, it is likely to have been optimized for oral bioavailability, as is the case for most HIV protease inhibitors. The compound is soluble in DMSO at high concentrations (approximately 100 mg/mL), and formulations have been developed for in vivo administration. Comprehensive PK parameters, such as half-life, Cmax, and AUC, would be determined in standard preclinical studies.
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| Toxicity/Toxicokinetics |
Specific toxicity data for DPC 681 is not available in the public domain. As a potent inhibitor of a viral protease, its safety profile would have been assessed in preclinical toxicology studies. The primary concern with any antiviral agent is its selectivity for the viral target over human proteins to avoid off-target toxicity. The compound's activity against mutant HIV strains suggests it has a robust interaction with the protease active site, which is a good indicator of target specificity. It is classified as a research compound and is not intended for human use.
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| References | |
| Additional Infomation |
DPC 681 is a significant research compound in the field of antiviral drug discovery. Its high potency and activity against drug-resistant HIV mutants make it a valuable tool for studying the structure-activity relationships of HIV protease inhibitors and for understanding the mechanisms of drug resistance. It has not received FDA approval and appears to have been developed as a research tool rather than a marketed drug.
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| Molecular Formula |
C35H48FN5O5S
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| Molecular Weight |
669.849531173706
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| Exact Mass |
669.336
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| CAS # |
284661-68-3
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| PubChem CID |
3083536
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| Appearance |
White to off-white solid powder
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| LogP |
4.7
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
47
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| Complexity |
1090
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O=S(C1=CC(N)=CC=C1)(N(C[C@@H](O)[C@H](CC2=CC=CC=C2)NC([C@H](C(C)(C)C)NC(CNCC3=CC=CC(F)=C3)=O)=O)CC(C)C)=O
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| InChi Key |
BHPRDABYBCABNU-NCNGZOBXSA-N
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| InChi Code |
InChI=1S/C35H48FN5O5S/c1-24(2)21-40(47(45,46)29-16-10-15-28(38)19-29)23-31(42)30(18-25-11-7-6-8-12-25)41(22-26-13-9-14-27(36)17-26)33(35(3,4)5)34(44)39-32(43)20-37/h6-17,19,24,30-31,33,42H,18,20-23,37-38H2,1-5H3,(H,39,43,44)/t30-,31?,33-/m0/s1
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| Chemical Name |
(2R)-N-(2-aminoacetyl)-2-[[(2S)-4-[(3-aminophenyl)sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]-[(3-fluorophenyl)methyl]amino]-3,3-dimethylbutanamide
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| Synonyms |
DPC681 DPC-681 DPC 681
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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 : ~100 mg/mL (~149.29 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 | 1.4929 mL | 7.4644 mL | 14.9287 mL | |
| 5 mM | 0.2986 mL | 1.4929 mL | 2.9857 mL | |
| 10 mM | 0.1493 mL | 0.7464 mL | 1.4929 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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