AC220
Inhibitor of FLT3
Structure
In Cells
In Model Organisms
SERP ratings and comments
SERP Ratings
SERP Comments:
This probe has a number of targets other than FLT3 and is active at 300 nM in human primary cell assays that do not express FLT3. If used as a target-selective probe in a study, this data should be supplemented by target knock-down and over expression of a constitutively active form to confirm involvement of the target.
(last updated: 22 May 2016 )
SERP Ratings
SERP Comments:
AC220 is potent and selective and has good PK characteristics. While activity in certain biochemical assays and cellular assays may be evident as low as 0.1-10 nM, drug-resistant models may require concentrations as high as 100-300 nM. It has been compared with and/or combined with other anticancer agents such as G-749 (FLT3 inhibitor) and JQ1 (BET protein antagonist) in various models, with resistant AML being an initial disease target in humans.
(last updated: 23 May 2016 )
SERP Ratings
SERP Comments:
No nonhuman ortholog potencies were reported. Acute oral dosing in mice was shown be tolerated (up to 300 mg/kg), though PK was linear up through 100 mg/kg. Repeat dosing was only performed at 10 mg/kg. RET, PDGFRA, PDGFRB, CSF1R are the only kinases within 10x. The recommended upper in vitro concentration is intended to minimize off-target RTK activity.
(last updated: 23 May 2016 )