| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 500mg |
| Targets |
BRD-0639 targets the interaction between protein arginine methyltransferase 5 (PRMT5) and its substrate adaptor via the PRMT5 binding motif (PBM). PRMT5 is a type II protein arginine methyltransferase that catalyzes the symmetric dimethylation of arginine residues on histones and non-histone proteins. By competitively inhibiting the PBM interaction, BRD-0639 disrupts PRMT5-substrate interactions and inhibits PBM-dependent PRMT5 functions.
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|---|---|
| ln Vitro |
Developed to enable the investigation of PBM-dependent PRMT5 activity and the creation of new PRMT5 inhibitors that specifically target these functions, BRD0639 is a first-in-class PBM competitive small molecule. With IC50s of 7.5 uM and 16 uM in permeabilized and viable cells, respectively, BRD0639 effectively competes for binding between full-length PRMT5 and RIOK1 proteins while engaging cellular targets. In the same subset of proteins that are likewise impacted by genetic modification of the PRMT5 binding motif (PBM) binding site, BRD0639 decreases SDMA [1].
In vitro, BRD-0639 inhibits the protein-peptide interaction between PRMT5 and PBM with an IC50 of 13.8 μM. It has IC50 values of 7.5 μM in permeabilized cells and 16 μM in living cells. BRD-0639 is a first-in-class PBM-competitive inhibitor that supports studies of PBM-dependent PRMT5 activity. |
| ln Vivo |
In vivo data for BRD-0639 is not extensively reported in publicly available sources. As a first-in-class inhibitor of PRMT5-PBM interactions, the compound has potential applications in animal models of cancer where PRMT5 plays a role. By disrupting PRMT5-substrate interactions, BRD-0639 could inhibit PRMT5-dependent oncogenic functions. However, specific published in vivo efficacy studies are not detailed in the current literature.
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| Enzyme Assay |
The in vitro PRMT5-PBM interaction assay for BRD-0639 uses purified PRMT5 and PBM peptides. The interaction is measured using techniques such as fluorescence polarization or surface plasmon resonance. IC50 values are calculated from dose-response curves. Cellular activity is assessed in permeabilized and living cells to determine the potency of the compound in a cellular context.
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| Cell Assay |
Cellular assays for BRD-0639 are conducted in cancer cell lines. Cells are treated with varying concentrations of BRD-0639. PRMT5-dependent methylation is measured by Western blotting using antibodies specific for symmetric dimethylarginine (SDMA). Cell viability and proliferation are measured using standard assays such as MTT or CellTiter-Glo. The compound's effects on PBM-dependent PRMT5 functions are evaluated.
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| Animal Protocol |
In vivo studies for BRD-0639 would typically involve xenograft mouse models of cancer. The compound would be administered via intraperitoneal or oral routes. Efficacy would be assessed by measuring tumor growth inhibition. However, specific published in vivo protocols for BRD-0639 are not available in the current literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for BRD-0639 is not extensively reported. The compound has a molecular weight of 475.95 g/mol and a molecular formula of C21H22ClN5O4S. It has a CAS number of 2760881-74-9. As a small molecule, it is expected to have moderate bioavailability. Detailed PK parameters such as half-life and bioavailability are not available.
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| Toxicity/Toxicokinetics |
Toxicity data for BRD-0639 is limited. As a research compound, BRD-0639 is intended for research use only and not for human therapeutic applications. Standard in vitro cytotoxicity assays and in vivo tolerability studies would be required for a complete toxicity assessment. The compound's first-in-class mechanism suggests a novel approach to targeting PRMT5.
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| References | |
| Additional Infomation |
BRD-0639 (BRD0639; CAS 2760881-74-9) is a first-in-class PBM-competitive inhibitor that disrupts the PRMT5-RIOK1 complex. It has IC50 values of 7.5 μM in permeabilized cells and 16 μM in living cells. It has a molecular formula of C21H22ClN5O4S and a molecular weight of 475.95 g/mol. BRD-0639 is a valuable research tool for studying PRMT5 biology.
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| Molecular Formula |
C21H22CLN5O4S
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|---|---|
| Exact Mass |
475.11
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| Elemental Analysis |
C, 53.00; H, 4.66; Cl, 7.45; N, 14.71; O, 13.45; S, 6.74
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| CAS # |
2760881-74-9
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| Related CAS # |
2760881-74-9; 2760909-27-9 (R-isomer);
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| PubChem CID |
156621384
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| Appearance |
Light yellow to brown solid powder
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| LogP |
1.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
32
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| Complexity |
857
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C(C=C(C=C1)NC(=O)[C@H](C)N2C(=O)C=C(C=N2)Cl)S(=O)(=O)NCCC3=CC=CC=N3
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| InChi Key |
BXDCFRRDENJUJM-HNNXBMFYSA-N
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| InChi Code |
InChI=1S/C21H22ClN5O4S/c1-14-6-7-18(26-21(29)15(2)27-20(28)11-16(22)13-24-27)12-19(14)32(30,31)25-10-8-17-5-3-4-9-23-17/h3-7,9,11-13,15,25H,8,10H2,1-2H3,(H,26,29)/t15-/m0/s1
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| Chemical Name |
(2S)-2-(4-chloro-6-oxopyridazin-1-yl)-N-[4-methyl-3-(2-pyridin-2-ylethylsulfamoyl)phenyl]propanamide
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| Synonyms |
BRD0639; BRD 0639; BRD-0639;
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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 : ~250 mg/mL (~525.27 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.37 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 (4.37 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 (4.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
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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