LP99 (LP-99) is a first-in-class BRD7/9 bromodomain inhibitor (Kd = 99 nM for BRD9) with anti-inflammatoryr activity. It inhibits IL‐6 secretion from THP‐1 cells in a dose‐dependent manner. The effect of LP99 on IL-6 expression demonstrates for the first time that a small-molecule BRD7/9 inhibitor may have a similar function and utility to IL-6 neutralizing antibodies, such as tocilizumab, in the treatment of rheumatoid arthritis.
Physicochemical Properties
| Molecular Formula | C26H30CLN3O4S |
| Molecular Weight | 516.053 |
| Exact Mass | 515.164 |
| CAS # | 1808951-93-0 |
| Related CAS # | 1808951-93-0 ;1808948-28-8; |
| PubChem CID | 91827372 |
| Appearance | Solid powder |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 726.6±70.0 °C at 760 mmHg |
| Flash Point | 393.2±35.7 °C |
| Vapour Pressure | 0.0±2.4 mmHg at 25°C |
| Index of Refraction | 1.644 |
| LogP | 4.15 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 35 |
| Complexity | 939 |
| Defined Atom Stereocenter Count | 2 |
| 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 |
| InChi Key | LVDRREOUMKACNJ-BKMJKUGQSA-N |
| 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 |
| Chemical Name | N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide |
| Synonyms | LP 99 LP-99 LP99 |
| 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 |
| 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
| 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]. |
| References |
[1]. LP99: Discovery and Synthesis of the First Selective BRD7/9 Bromodomain Inhibitor. Angew Chem Int Ed Engl. 2015 May 18;54(21):6217-21. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~50 mg/mL (~96.89 mM) |
| 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 |