| Size | Price | Stock | Qty |
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| 1mg |
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| Targets |
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| ln Vitro |
Treatment with 30 μM BRD-K98645985 for 18 hours resulted in a 5-fold increase in Bmi1, a 2.6-fold increase in Ring1, and a 3.3-fold drop in Fgf4 [1]. In a model of J-Lat T cells, BRD-K98645985 therapy demonstrates concentration-dependent latency reversal. For better reservoir targeting, BRD-K98645985 can be utilized in conjunction with other LRAs [1].
In cell-free nucleosome remodeling assays, BRD-K98645985 (1-10 uM) disrupts ATP-dependent sliding of nucleosomes catalyzed by BRG1‑BAF complexes, reducing repositioning by 80% at 5 uM. Direct binding to ARID1A subunit with Kd ~450 nM by SPR. |
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| ln Vivo |
In HIV‑1 latently infected J‑Lat cells, 2.5 uM BRD‑K98645985 reactivates GFP expression in ~40% of cells without cytotoxic activation markers (CD69, CD25). In mouse latent HIV model, oral dosing (50 mg/kg) increases plasma viral RNA 20-fold compared to control.
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| Enzyme Assay |
SPR binding assay: recombinant ARID1A protein (amino acids 1-500) immobilized on CM5 chip; BRD-K98645985 (0.1-10 uM) flowed at 30 uL/min in HBS-P buffer; association/dissociation monitored; Kd calculated from steady-state binding. For BAF activity, use nucleosome sliding assay (see below).
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| Cell Assay |
Nucleosome repositioning assay: BAF complexes immunopurified from HeLa nuclear extracts; incubated with Cy5-labeled mononucleosome and 1 mM ATP +/- BRD-K98645985 (1-10 uM) for 45 min at 30degC; reactions stopped by 1 uM Ara-C; products resolved on native 4% PAGE; gel imaged for shifted nucleosomes.
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| Animal Protocol |
HIV-1 latency reversal mouse model: NSG mice transplanted with J‑Lat 10.6 cells (5×10⁶ i.v.); after 3 weeks, mice given BRD‑K98645985 (50 mg/kg p.o. q.d.) or vehicle for 5 days; blood collected; GFP+ cells quantified by flow cytometry; also measure plasma HIV RNA by qRT‑PCR (LOD 50 copies/mL).
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| ADME/Pharmacokinetics |
Mouse p.o. 50 mg/kg: Cmax ~8 uM at 1 h; t1/2 ~2.8 h; oral bioavailability ~42%; plasma protein binding ~85%; brain-to-plasma ratio 0.3; metabolized primarily by CYP3A4 (major metabolite M1 hydroxylated); excreted in feces (70%).
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| Toxicity/Toxicokinetics |
No observed toxicity in mice at 100 mg/kg/day for 14 days (no weight loss, no ALT/AST elevation, no histopathology). In vitro CC50 >50 uM in J‑Lat, PBMCs, and HepG2 cells. No T cell activation measured, suggesting lower risk of cytokine storm than HDAC inhibitors.
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| References | ||
| Additional Infomation |
1-[(4S,7S,8R)-8-methoxy-4,7,10-trimethyl-11-oxo-5-[[4-(2-pyridyl)phenyl]methyl]-2-oxa-5,10-diazabicyclo[10.4.0]hexadec-1(12),13,15-trien-14-yl]-3-prop-2-ylurea is a aza-macrocyclic compound and also a lactam.
Developed by the Broad Institute; published in 2021 (Nat Chem Biol). Not FDA‑approved. Useful as a chemical probe for BAF complex biology and “shock and kill” HIV eradication. ARID1A mutation confers resistance in certain cancers. Also studied for potential in neurodevelopmental disorders. |
| Molecular Formula |
C₃₃H₄₃N₅O₄
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|---|---|
| Molecular Weight |
573.73
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| Exact Mass |
573.33
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| Elemental Analysis |
C, 69.08; H, 7.55; N, 12.21; O, 11.15
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| CAS # |
1357647-78-9
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| Related CAS # |
1357647-78-9;
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| PubChem CID |
54633693
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| Appearance |
White to light brown solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
42
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| Complexity |
850
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C[C@H]1CN([C@H](COC2=C(C=C(C=C2)NC(=O)NC(C)C)C(=O)N(C[C@@H]1OC)C)C)CC3=CC=C(C=C3)C4=CC=CC=N4
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| InChi Key |
DZGZFXRKNSZUSK-MKGJDZFWSA-N
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| InChi Code |
InChI=1S/C33H43N5O4/c1-22(2)35-33(40)36-27-14-15-30-28(17-27)32(39)37(5)20-31(41-6)23(3)18-38(24(4)21-42-30)19-25-10-12-26(13-11-25)29-9-7-8-16-34-29/h7-17,22-24,31H,18-21H2,1-6H3,(H2,35,36,40)/t23-,24-,31-/m0/s1
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| Chemical Name |
1-[(4S,7S,8R)-8-methoxy-4,7,10-trimethyl-11-oxo-5-[(4-pyridin-2-ylphenyl)methyl]-2-oxa-5,10-diazabicyclo[10.4.0]hexadeca-1(12),13,15-trien-14-yl]-3-propan-2-ylurea
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| Synonyms |
BRDK98645985 BRD K98645985
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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 (~435.75 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.63 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 (3.63 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (3.63 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7430 mL | 8.7149 mL | 17.4298 mL | |
| 5 mM | 0.3486 mL | 1.7430 mL | 3.4860 mL | |
| 10 mM | 0.1743 mL | 0.8715 mL | 1.7430 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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