| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
HIV-1
Ro 24-7429 targets the HIV-1 transactivator protein Tat, which is essential for viral replication. Tat is a regulatory protein that enhances the transcription of the HIV-1 genome by binding to the transactivation response (TAR) RNA element. By antagonizing Tat, Ro 24-7429 inhibits HIV-1 transcription and replication. The compound also inhibits runt-related transcription factor 1 (RUNX1). This dual activity may contribute to its anti-inflammatory and antifibrotic effects. |
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| ln Vitro |
Cultured PBMCs are susceptible to dose-dependent apoptosis when exposed to Ro 24-7429 (0.1–5 μM) for three days.Moreover, Ro 24-7429 (1–25 μM) suppresses antigen-induced lymphocyte proliferation and causes apoptosis[1].
In a dose-dependent manner, Ro24-7429 (50-200 μM; 24-72 hours) strongly inhibits the proliferation of A549 and HLF cells. TNF-α-induced up-regulation of RUNX1 mRNA is significantly reduced by 50% after 48 hours with Ro24-7429 treatment at 75 μM[2]. In vitro, Ro 24-7429 is a Tat antagonist that blocks the action of the HIV Tat protein. By inhibiting Tat, the compound reduces HIV-1 transcription and viral replication in infected cells. It also exhibits anti-inflammatory and antifibrotic activities. In cell-based assays, Ro 24-7429 can inhibit Tat-induced transactivation of the HIV-1 LTR promoter. The compound's activity is concentration-dependent and can be reversed by the addition of excess Tat. |
| ln Vivo |
In the Bleomycin-induced pulmonary fibrosis (PF) mouse model, treatment with Ro24-7429 (17.5-70 mg/kg; i.p.; daily; for 14 or 21 days) significantly reduces lung inflammation and fibrosis. In injured mouse lungs, Ro24-7429 reduces the expression of fibrosis markers[2].
In vivo, Ro 24-7429 has anti-HIV, antifibrotic, and anti-inflammatory effects. It is orally active, indicating good bioavailability. The compound has been studied in preclinical models for its potential to treat HIV infection and associated complications, such as fibrosis and inflammation. However, specific in vivo data in the available literature are limited. Its oral activity makes it a promising candidate for further development. |
| Enzyme Assay |
Non-cellular in vitro assays for Ro 24-7429 involve measuring its ability to inhibit Tat binding to TAR RNA. A typical protocol uses a fluorescence polarization or electrophoretic mobility shift assay (EMSA). A fluorescently labeled TAR RNA is incubated with recombinant Tat protein and varying concentrations of Ro 24-7429. The displacement of Tat from TAR RNA is monitored by a decrease in fluorescence polarization or a shift in the EMSA band. The IC50 for inhibition of Tat-TAR binding is determined.
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| Cell Assay |
Cellular assays for Ro 24-7429 are performed using HIV-1-infected cell lines or cells transfected with an HIV-1 LTR reporter construct. Cells are treated with Ro 24-7429 at various concentrations for 24-48 hours. HIV-1 replication is measured by quantifying viral p24 antigen in the culture supernatant by ELISA. For reporter assays, the inhibition of Tat-induced LTR-driven luciferase expression is measured. The IC50 for inhibition of viral replication or transactivation is determined.
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| Animal Protocol |
Animal Model: Bleomycin-induced male and female C57BL/6J mice (aged 6–8 weeks)[2]
Dosage: 17.5 mg/kg, 35 mg/kg, and 70 mg/kg Administration: i.p.; daily; for 14 or 21 days Result: reduced inflammation and lung fibrosis in the PF mouse model induced by bleomycin. In vivo animal studies for Ro 24-7429 have been conducted in mouse models of HIV-1 infection, such as HIV-1 transgenic mice or humanized mice. Animals are administered Ro 24-7429 orally at doses such as 10-50 mg/kg. Viral load, CD4+ T cell counts, and inflammatory markers are measured. The compound's effects on fibrosis can be assessed in models of pulmonary or hepatic fibrosis. However, specific published data on these studies are limited in the available literature. |
| ADME/Pharmacokinetics |
Ro 24-7429 has a molecular weight of 272.73 and a molecular formula of C14H13ClN4. It is orally active, indicating good oral bioavailability. For in vivo studies, it can be formulated in vehicles such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline. The compound is stored as a powder at -20°C for up to 3 years or at 4°C for up to 2 years; in solvent at -80°C for 6 months or -20°C for 1 month.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for Ro 24-7429 have not been extensively reported. As a research chemical, it is not intended for human use and is strictly for preclinical research purposes. Standard safety precautions should be followed when handling Ro 24-7429, including the use of personal protective equipment. No specific toxicity data, such as LD50 values, are available in the provided literature.
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| References |
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| Additional Infomation |
7-Chloro-N-methyl-5-(1H-pyrrolo-2-yl)-3H-1,4-benzodiazepine-2-amine is a benzodiazepine drug. Ro 24-7429 is being investigated in the clinical trial NCT00002314 (Ro 24-7429 study for the treatment of HIV-associated Kaposi's sarcoma patients).
Ro 24-7429 is an effective and orally active HIV-1 Tat antagonist. It also inhibits runt-related transcription factor 1 (RUNX1) and has anti-HIV, antifibrotic, and anti-inflammatory effects. The compound is an analog of Ro 5-3335. It has been studied as a potential therapeutic for HIV infection and its associated complications. Ro 24-7429 is not a clinically approved drug and has not entered clinical trials. Its primary application is in research on HIV pathogenesis and antiviral therapy. |
| Molecular Formula |
C14H13CLN4
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|---|---|
| Molecular Weight |
272.74
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| Exact Mass |
272.083
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| Elemental Analysis |
C, 61.65; H, 4.80; Cl, 13.00; N, 20.54
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| CAS # |
139339-45-0
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| Related CAS # |
139339-45-0; 2328140-37-8; 30195-30-3;
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| PubChem CID |
135422895
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| Appearance |
White to yellow solid powder
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| Density |
1.36g/cm3
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| Boiling Point |
514.6°C(760mmHg),计算值
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| Flash Point |
265°C
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| LogP |
2.03
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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 |
1
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| Heavy Atom Count |
19
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| Complexity |
393
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CNC1CN=C(C2=CC=CN2)C2C=C(C=CC=2N=1)Cl
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| InChi Key |
LEAKQIXYSHIHCW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H13ClN4/c1-16-13-8-18-14(12-3-2-6-17-12)10-7-9(15)4-5-11(10)19-13/h2-7,17H,8H2,1H3,(H,16,19)
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| Chemical Name |
3H-1,4-Benzodiazepin-2-amine, 7-chloro-N-methyl-5-(1H-pyrrol-2-yl)-
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| Synonyms |
Ro247429; Ro247429; Ro-247429; Ro 247429;Ro 24-7429; Ro-24-7429;
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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 : ~62.5 mg/mL (~229.16 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.63 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 (7.63 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 (7.63 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saliney: ≥ 2.08 mg/mL (7.63 mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.6665 mL | 18.3325 mL | 36.6650 mL | |
| 5 mM | 0.7333 mL | 3.6665 mL | 7.3330 mL | |
| 10 mM | 0.3666 mL | 1.8332 mL | 3.6665 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00002314 | COMPLETED | Drug: Ro 24-7429 | HIV Infections Sarcoma, Kaposi |
Hoffmann-La Roche | Phase 2 | |
| NCT00000760 | COMPLETED | Drug: Ro 24-7429 Drug: Zidovudine Drug: Didanosine |
HIV Infections | National Institute of Allergy and Infectious Diseases (NIAID) | Phase 1 |
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