Rational design based on a pharmacophore of CCR2 antagonists reported in the literature identified lead compound 9a with potent inhibitory activity against human CCR2 (hCCR2) but moderate activity against murine CCR2 (mCCR2). Modification on 9a led to the discovery of a potent CCR2 antagonist 21 (INCB3344) with IC(50) values of 5.1 nM (hCCR2) and 9.5 nM (mCCR2) in binding antagonism and 3.8 nM more ..
Target
Tested Compound:
Description:
Title: Discovery of INCB3344, a potent, selective and orally bioavailable antagonist of human and murine CCR2.
Abstract: Rational design based on a pharmacophore of CCR2 antagonists reported in the literature identified lead compound 9a with potent inhibitory activity against human CCR2 (hCCR2) but moderate activity against murine CCR2 (mCCR2). Modification on 9a led to the discovery of a potent CCR2 antagonist 21 (INCB3344) with IC(50) values of 5.1 nM (hCCR2) and 9.5 nM (mCCR2) in binding antagonism and 3.8 nM (hCCR2) and 7.8 nM (mCCR2) in antagonism of chemotaxis activity. INCB3344 exhibited >100-fold selectivity over other homologous chemokine receptors, a free fraction of 24% in human serum and 15% in mouse serum, and an oral bioavailability of 47% in mice, suitable as a tool compound for target validation in rodent models.
(PMID: 21036044)
Abstract: Rational design based on a pharmacophore of CCR2 antagonists reported in the literature identified lead compound 9a with potent inhibitory activity against human CCR2 (hCCR2) but moderate activity against murine CCR2 (mCCR2). Modification on 9a led to the discovery of a potent CCR2 antagonist 21 (INCB3344) with IC(50) values of 5.1 nM (hCCR2) and 9.5 nM (mCCR2) in binding antagonism and 3.8 nM (hCCR2) and 7.8 nM (mCCR2) in antagonism of chemotaxis activity. INCB3344 exhibited >100-fold selectivity over other homologous chemokine receptors, a free fraction of 24% in human serum and 15% in mouse serum, and an oral bioavailability of 47% in mice, suitable as a tool compound for target validation in rodent models.
(PMID: 21036044)
Categorized Comment
ChEMBL Assay Type: Binding
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 12406
ChEMBL target type: Target is a single protein chain
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 12406
ChEMBL target type: Target is a single protein chain
Result Definitions
| TID | Name | Description | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||
| 1 | IC50* | IC50 PubChem standard value |  | Float | μM | |
| 2 | IC50 activity comment | IC50 activity comment | String | |||
| 3 | IC50 standard flag | IC50 standard flag | | Integer | ||
| 4 | IC50 qualifier | IC50 qualifier | String | |||
| 5 | IC50 published value | IC50 published value | | Float | nM | |
| 6 | IC50 standard value | IC50 standard value | | Float | nM |
* Activity Concentration.
Data Table (Concise)
Classification
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