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| Targets |
RUNX1-CBFβ interaction[1]
RUNX1-CBFβ interaction. Ro5-3335 is an inhibitor of the core binding factor (CBF) that represses RUNX1/CBFβ-dependent transactivation. RUNX1 (also known as AML1) is a transcription factor that forms a heterodimeric complex with CBFβ, which is essential for its DNA binding and transcriptional activity. The RUNX1-CBFβ complex is critical for normal hematopoiesis and is frequently disrupted by chromosomal translocations in acute myeloid leukemia (AML) and other leukemias. By inhibiting the RUNX1-CBFβ interaction, Ro5-3335 blocks RUNX1-mediated transcription, leading to growth inhibition of leukemia cells with CBF fusion proteins. |
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| ln Vitro |
Ro5-3335 exhibits antiproliferative effect against human CBF leukemia cell lines, as demonstrated by its IC50 values of 1.1 μM, 21.7 μM, and 17.3 μM for ME-1, Kasumi-1, and REH, respectively[1]. In zebrafish embryos, Ro5-3335 prevents final hematopoiesis [1]. Although Ro5-3335 alters the complex's structure or widens the gap between RUNX1 and CBFβ, it does not entirely dissolve the RUNX1-CBFβ interaction[1].
Ro5-3335 demonstrates potent in vitro activity against human leukemia cell lines with CBF fusion proteins. The compound preferentially kills these cells with IC50 values of 1.1 μM (ME-1), 21.7 μM (Kasumi-1), and 17.3 μM (REH). In reporter assays, Ro5-3335 represses RUNX1/CBFβ-dependent transactivation. The compound's selectivity for CBF fusion-containing cells over normal cells makes it a valuable tool for studying CBF leukemia. Further detailed in vitro data, including selectivity profiles and cellular effects, are available in the primary literature. |
| ln Vivo |
In zebrafish models, Ro5-3335 has been found to be an inhibitor of RUNX1–CBFβ function[1]. ?A RUNX1-ETO transgenic zebrafish's preleukemic phenotype is salvaged by Ro5-3335[1]. ?In a mouse CBFB-MYH11 leukemia model, Ro5-3335 (300 mg/kg/d; po; for 30 days) lowers the burden of leukemia[1].
In vivo activity of Ro5-3335 has been demonstrated in zebrafish embryos, where the compound inhibits runx1-dependent hematopoiesis. This model system has been used to study the role of RUNX1-CBFβ in hematopoietic development. However, specific in vivo data in mammalian models, including efficacy in leukemia models, pharmacokinetics, and toxicity, are not extensively detailed in the available literature summary. |
| Enzyme Assay |
Binding and functional assays for Ro5-3335 are performed to evaluate inhibition of the RUNX1-CBFβ interaction. The compound's ability to inhibit RUNX1/CBFβ-dependent transactivation is assessed in reporter assays, where a luciferase reporter under the control of RUNX1-binding sites is used. The compound's selectivity for CBF fusion-containing cells is confirmed in cell viability assays.
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| Cell Assay |
Cell-based assays for Ro5-3335 are conducted using human leukemia cell lines with CBF fusion proteins, including ME-1, Kasumi-1, and REH. Cells are treated with the compound at various concentrations, and cell viability is assessed by MTT or other assays. IC50 values of 1.1 μM, 21.7 μM, and 17.3 μM are determined for ME-1, Kasumi-1, and REH cells, respectively. The compound's effects on RUNX1 target gene expression can be assessed by qPCR or RNA-seq.
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| Animal Protocol |
Animal/Disease Models: C57BL/6 mice (leukemic model)[1]
Doses: 300 mg/kg Route of Administration: Oral administration; daily; for 30 days Experimental Results: decreased the number of c-kit+ cells in the transplanted mice and leukemic cell infiltration in the livers, bone marrow and spleen. In vivo studies for Ro5-3335 have been performed in zebrafish embryos to assess the compound's effects on hematopoiesis. Zebrafish embryos are treated with the compound, and the development of hematopoietic cells is assessed by in situ hybridization or transgenic reporter expression. However, specific in vivo data in mammalian models are not extensively detailed in the available literature summary. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Ro5-3335 are not extensively reported in the available literature. As a small molecule with a molecular weight of 259.69, the compound would be expected to have reasonable bioavailability if administered appropriately, though this would need to be confirmed experimentally. Storage recommendations include refrigeration (0-10°C) for long-term storage. The compound is a white, light red or green crystalline powder with a melting point of 256°C (dec.).
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| Toxicity/Toxicokinetics |
As a research chemical, Ro5-3335 is not intended for human or veterinary use, and comprehensive toxicological data are not extensively reported in the available literature. Standard laboratory safety precautions should be followed when handling the compound, including the use of appropriate personal protective equipment (gloves, lab coat, safety glasses) and proper ventilation.
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| References | |
| Additional Infomation |
Ro 5-3335 is a 1,4-benzodiazepine ketone compound, a derivative of nordiazepam, in which the phenyl substituent is replaced by a 1H-pyrrole-2-yl group. It inhibits HIV-1 gene expression at the transcriptional level by interfering with Tat-mediated transcriptional activation. It possesses various activities including antitumor, anti-HIV-1, RUNX1, and HIV-1 Tat inhibition. It is a 1,4-benzodiazepine ketone compound, belonging to the organochlorine compound family and also a pyrrole class of compounds.
Ro5-3335 is a core binding factor (CBF) inhibitor that acts as a RUNX1-CBFβ interaction inhibitor. It preferentially kills human leukemia cell lines with CBF fusion proteins and is a valuable tool for studying the role of RUNX1-CBFβ in leukemia and hematopoiesis. The compound is not approved for clinical use and is supplied for research purposes only. Synonyms include Ro 5-3335 and CBFβ-Runx1 inhibitor II. The compound is available from multiple chemical suppliers. |
| Molecular Formula |
C₁₃H₁₀CLN₃O
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|---|---|
| Molecular Weight |
259.691
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| Exact Mass |
259.051
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| CAS # |
30195-30-3
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| Related CAS # |
139339-45-0; 2328140-37-8 ;30195-30-3;
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| PubChem CID |
64983
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.46g/cm3
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| Boiling Point |
501.6ºC at 760mmHg
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| Melting Point |
256 °C (分解)
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| Flash Point |
257.1ºC
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| Index of Refraction |
1.712
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| LogP |
2.031
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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 |
18
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| Complexity |
371
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
XWNMORIHKRROGW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H10ClN3O/c14-8-3-4-10-9(6-8)13(11-2-1-5-15-11)16-7-12(18)17-10/h1-6,15H,7H2,(H,17,18)
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| Chemical Name |
7-Chloro-1,3-dihydro-5-(1H-pyrrol-2-yl)-2H-1,4-benzodiazepin-2-one
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| Synonyms |
Ro5-3335 Ro 5 3335 CBFβ-Runx1 inhibitor II Ro 5-3335
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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 (~385.07 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.63 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 25.0 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: ≥ 2.5 mg/mL (9.63 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.8507 mL | 19.2537 mL | 38.5075 mL | |
| 5 mM | 0.7701 mL | 3.8507 mL | 7.7015 mL | |
| 10 mM | 0.3851 mL | 1.9254 mL | 3.8507 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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