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| 25mg |
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| 50mg |
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Brr2 inhibitor C9 (no formal name but also known as Brr2 Inhibitor 9 ) is an allosteric inhibitor of the spliceosomal RNA helicase Brr2.
| 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 |
| 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)
|
| 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. View More
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. |
| 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 |
*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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