Activating mutations in the receptor tyrosine kinase FLT3 are present in up to approximately 30% of acute myeloid leukemia (AML) patients, implicating FLT3 as a driver of the disease and therefore as a target for therapy. We report the characterization of AC220, a second-generation FLT3 inhibitor, and a comparison of AC220 with the first-generation FLT3 inhibitors CEP-701, MLN-518, PKC-412, more ..
BioActive Compounds: 7
Description:
Title: AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).
Abstract: Activating mutations in the receptor tyrosine kinase FLT3 are present in up to approximately 30% of acute myeloid leukemia (AML) patients, implicating FLT3 as a driver of the disease and therefore as a target for therapy. We report the characterization of AC220, a second-generation FLT3 inhibitor, and a comparison of AC220 with the first-generation FLT3 inhibitors CEP-701, MLN-518, PKC-412, sorafenib, and sunitinib. AC220 exhibits low nanomolar potency in biochemical and cellular assays and exceptional kinase selectivity, and in animal models is efficacious at doses as low as 1 mg/kg given orally once daily. The data reveal that the combination of excellent potency, selectivity, and pharmacokinetic properties is unique to AC220, which therefore is the first drug candidate with a profile that matches the characteristics desirable for a clinical FLT3 inhibitor.
(PMID: 19654408)
Abstract: Activating mutations in the receptor tyrosine kinase FLT3 are present in up to approximately 30% of acute myeloid leukemia (AML) patients, implicating FLT3 as a driver of the disease and therefore as a target for therapy. We report the characterization of AC220, a second-generation FLT3 inhibitor, and a comparison of AC220 with the first-generation FLT3 inhibitors CEP-701, MLN-518, PKC-412, sorafenib, and sunitinib. AC220 exhibits low nanomolar potency in biochemical and cellular assays and exceptional kinase selectivity, and in animal models is efficacious at doses as low as 1 mg/kg given orally once daily. The data reveal that the combination of excellent potency, selectivity, and pharmacokinetic properties is unique to AC220, which therefore is the first drug candidate with a profile that matches the characteristics desirable for a clinical FLT3 inhibitor.
(PMID: 19654408)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Putative Target:
ChEMBL Target ID: 50594
Target Type: ORGANISM
Pref Name: Mus musculus
Organism: Mus musculus
Tax ID: 10090
Confidence: Target assigned is non-molecular
Relationship Type: Non-molecular target assigned
Putative Target:
ChEMBL Target ID: 50594
Target Type: ORGANISM
Pref Name: Mus musculus
Organism: Mus musculus
Tax ID: 10090
Confidence: Target assigned is non-molecular
Relationship Type: Non-molecular target assigned
Categorized Comment
ChEMBL Assay Type: ADMET
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Assay Test Type: In vivo
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Assay Test Type: In vivo
Result Definitions
| TID | Name | Description | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||
| 1 | Cmax activity comment | Cmax activity comment | String | |||
| 2 | Cmax standard flag | Cmax standard flag |  | Integer | ||
| 3 | Cmax qualifier | Cmax qualifier | String | |||
| 4 | Cmax published value | Cmax published value | | Float | nM | |
| 5 | Cmax standard value | Cmax standard value | | Float | nM |
Data Table (Concise)
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