LP99   Click here for help

GtoPdb Ligand ID: 8572

Synonyms: compound 60 [PMID: 25864491]
PDB Ligand
Compound class: Synthetic organic
Comment: LP99 is a selective inhibitor of the bromodomain-containing proteins BRD7 and BRD9 [1], proteins which participate in chromatin remodelling as part of the SWI/SNF complex. LP99 is a novel and useful chemical probe for investigating BRD7/9 function. This is a compound from the Structural Genomics Consortium's (SGC) Epigenetics Probes Collection.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 96.86
Molecular weight 515.16
XLogP 5.38
No. Lipinski's rules broken 1
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Canonical SMILES Clc1ccc(cc1)C1C(CCC(=O)N1c1ccc2c(c1)n(C)c(=O)cc2C)NS(=O)(=O)CC(C)C
Isomeric SMILES Clc1ccc(cc1)[C@@H]1[C@H](CCC(=O)N1c1ccc2c(c1)n(C)c(=O)cc2C)NS(=O)(=O)CC(C)C
InChI 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
Bioactivity Comments
The activity of LP99 is stereo-specific. The alternative (2S, 3R)-LP99 isomer does not bind BRD9 [1]. In vitro experiments using LPS-activated THP-1 monocytes show that BRD7/9 plays a role in regulating pro-inflammatory cytokine secretion [1].
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
bromodomain containing 9 Primary target of this compound Hs Inhibitor Inhibition 7.0 pKd - 1
pKd 7.0 (Kd 9.9x10-8 M) [1]
Description: Isothermal titration calorimetry (ITC) assay
bromodomain containing 7 Hs Inhibitor Inhibition ~6.0 pKd - 1
pKd ~6.0 (Kd ~1x10-6 M) [1]
Description: Based on binding of BRD7 being 10-fold lower than for BRD9