Brr2 inhibitor C9 (no formal name but also known as Brr2 Inhibitor 9 ) is an allosteric inhibitor of the spliceosomal RNA helicase Brr2.
Physicochemical Properties
| Molecular Formula | C24H20N4O3S |
| Molecular Weight | 444.509 |
| Exact Mass | 444.13 |
| Elemental Analysis | C, 64.85; H, 4.54; N, 12.60; O, 10.80; S, 7.21 |
| CAS # | 2104030-82-0 |
| PubChem CID | 132585219 |
| Appearance | Solid powder |
| Density | 1.44±0.1 g/cm3(Predicted) |
| Boiling Point | 777.4±60.0 °C(Predicted) |
| LogP | 2 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 32 |
| Complexity | 779 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S1C=NC=C1COC1=CC=CC(=C1)N1C(NC2=CC(N(CC3C=CC=CC=3)C=C2C1)=O)=O |
| InChi Key | GAWVULNDIBAUHU-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C24H20N4O3S/c29-23-10-22-18(13-27(23)12-17-5-2-1-3-6-17)14-28(24(30)26-22)19-7-4-8-20(9-19)31-15-21-11-25-16-32-21/h1-11,13,16H,12,14-15H2,(H,26,30) |
| Chemical Name | 6-benzyl-3-[3-(1,3-thiazol-5-ylmethoxy)phenyl]-1,4-dihydropyrido[4,3-d]pyrimidine-2,7-dione |
| Synonyms | GUN30820; GUN 30820; GUN-30820; Brr2 Inhibitor 9; Brr2 inhibitor C9; Brr2-IN-3 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Brr2 |
| ln Vitro | Brr2 is an RNA helicase belonging to the Ski2-like subfamily and an essential component of spliceosome. Brr2 catalyzes an ATP-dependent unwinding of the U4/U6 RNA duplex, which is a critical step for spliceosomal activation. An HTS campaign using an RNA-dependent ATPase assay and initial SAR study identified two different Brr2 inhibitors, 3 and 12. Cocrystal structures revealed 3 binds to an unexpected allosteric site between the C-terminal and the N-terminal helicase cassettes, while 12 binds an RNA-binding site inside the N-terminal cassette. Selectivity profiling indicated the allosteric inhibitor 3 is more Brr2-selective than the RNA site binder 12. Chemical optimization of 3 using SBDD culminated in the discovery of the potent and selective Brr2 inhibitor 9 with helicase inhibitory activity. Our findings demonstrate an effective strategy to explore selective inhibitors for helicases, and 9 could be a promising starting point for exploring molecular probes to elucidate biological functions and the therapeutic relevance of Brr2.[1] |
| References |
[1]. Discovery of Allosteric Inhibitors Targeting the Spliceosomal RNA Helicase Brr2. J Med Chem. 2017;60(13):5759-5771. |
Solubility Data
| Solubility (In Vitro) |
DMSO: ~89 mg/mL (~200.2 mM) Ethanol: ~2 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.62 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 (5.62 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.68 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2497 mL | 11.2483 mL | 22.4967 mL | |
| 5 mM | 0.4499 mL | 2.2497 mL | 4.4993 mL | |
| 10 mM | 0.2250 mL | 1.1248 mL | 2.2497 mL |