| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Targets |
LP99 targets the bromodomains of BRD7 and BRD9. It binds with Kd values of 99 nM for BRD9 and 909 nM for BRD7. It exhibits selectivity for BRD7/9 over a panel of 48 bromodomains (at 10 μM). By inhibiting these bromodomains, it disrupts chromatin interactions.
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| ln Vitro |
The connection between BRD9 and chromatin is disrupted by LP99 at a concentration of 0.8 μM. HEK293 cells were used to express fluorescently tagged histone H3.3- and H4-HaloTag fusion proteins, as well as BRD7- and BRD9-NanoLuc luciferase fusion proteins. In the H3.3 and H4 systems, the addition of LP99 decreased the BRET of BRD7 and BRD9 in a dose-dependent way, with the cellular IC50 values for both histones falling in the low micromolar range. Testing for cytotoxicity in U2OS cells over 24 and 72 hours revealed that the inhibitor was safe at concentrations less than 33 μM. THP-1 cells' production of IL-6 is dose-dependently inhibited by LP99[1].
LP99 binds to BRD9 with a Kd of 99 nM and to BRD7 with a Kd of 909 nM. It disrupts BRD9 interactions with chromatin at a concentration of 0.8 μM. It inhibits IL-6 secretion from THP-1 cells in a dose-dependent manner. |
| ln Vivo |
LP99 has anti-inflammatory activity in vivo. It suppresses IL-6 secretion. It has been studied for its anti-inflammatory activity and potential applications in arthritis. In vivo studies support its application in studying chromatin regulation and inflammation.
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| Enzyme Assay |
Non-cell-based assays for LP99 include isothermal titration calorimetry (ITC) to determine binding affinity (Kd) to BRD7 and BRD9 bromodomains. AlphaScreen or FRET-based competition assays may also be used. The compound is incubated with purified bromodomain proteins and labeled ligands, and binding is measured by signal changes. Selectivity profiling is performed against panels of bromodomains.
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| Cell Assay |
Cellular assays for LP99 utilize THP-1 cells (human monocytic cell line) or other cell lines expressing BRD7 and BRD9. Cells are treated with the compound at various concentrations. IL-6 secretion is measured by ELISA following stimulation. Chromatin immunoprecipitation (ChIP) assays may be used to assess disruption of BRD9 interactions with chromatin.
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| Animal Protocol |
In vivo animal models for LP99 include models of inflammation such as arthritis models. The compound is administered orally or via other routes. Inflammatory markers are measured, and disease severity is assessed. The compound's anti-inflammatory activity is evaluated. Detailed protocols are not extensively reported.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of LP99 include CAS number 1808951-93-0. The compound is a small molecule bromodomain inhibitor. Detailed PK parameters such as half-life and bioavailability are not extensively reported. The compound is an epigenetic probe for research use.
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| Toxicity/Toxicokinetics |
LP99 is a first-in-class BRD7/9 bromodomain inhibitor. It has anti-inflammatory activity. Detailed toxicity data are not extensively reported. The compound is a research tool for studying chromatin regulation, inflammation, and bromodomain biology. It has potential applications in arthritis and other inflammatory conditions.
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| References | |
| Additional Infomation |
LP99 is a potent and selective inhibitor of BRD7 and BRD9 bromodomains. It has CAS number 1808951-93-0. It has a Kd of 99 nM for BRD9 and 909 nM for BRD7. It disrupts BRD9 interactions with chromatin at 0.8 μM. It inhibits IL-6 secretion and has anti-inflammatory activity.
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| Molecular Formula |
C26H30CLN3O4S
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|---|---|
| Molecular Weight |
516.053
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| Exact Mass |
515.164
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| CAS # |
1808951-93-0
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| Related CAS # |
1808951-93-0 ;1808948-28-8;
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| PubChem CID |
91827372
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| Appearance |
Solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
726.6±70.0 °C at 760 mmHg
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| Flash Point |
393.2±35.7 °C
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| Vapour Pressure |
0.0±2.4 mmHg at 25°C
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| Index of Refraction |
1.644
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| LogP |
4.15
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
939
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC1=CC(=O)N(C2=C1C=CC(=C2)N3[C@@H]([C@H](CCC3=O)NS(=O)(=O)CC(C)C)C4=CC=C(C=C4)Cl)C
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| InChi Key |
LVDRREOUMKACNJ-BKMJKUGQSA-N
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| InChi Code |
InChI=1S/C26H30ClN3O4S/c1-16(2)15-35(33,34)28-22-11-12-24(31)30(26(22)18-5-7-19(27)8-6-18)20-9-10-21-17(3)13-25(32)29(4)23(21)14-20/h5-10,13-14,16,22,26,28H,11-12,15H2,1-4H3/t22-,26+/m0/s1
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| Chemical Name |
N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide
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| Synonyms |
LP 99 LP-99 LP99
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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 : ~50 mg/mL (~96.89 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.84 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 (4.84 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 | 1.9378 mL | 9.6890 mL | 19.3780 mL | |
| 5 mM | 0.3876 mL | 1.9378 mL | 3.8756 mL | |
| 10 mM | 0.1938 mL | 0.9689 mL | 1.9378 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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