flt

PROTAC FLT-3 degrader 1 is a PROTAC FLT-3 degrader of internal tandem duplication (ITD) with an IC50 of 0.6 nM and exhibits anti-proliferative activity.

PROTAC FLT3/CDK9 degrader-1, a potent dual degrader of FLT3 and CDK9, effectively induces apoptosis and targets protein degradation of FLT3 and CDK9. This compound holds research potential for FLT3-ITD mutated AML [1].

PROTACFLT-3degrader 3 (compound 35) is a PROTAC degrader of FLT. It exhibits antiproliferative activity, with an IC50 value of 7.55 nM in MV4-11 cells.

FLT3 Ligand-Linker Conjugate 1 consists of an FLT3 ligand and a PROTAC linker that can recruit E3 ligase VHL. This conjugate is useful for synthesizing PROTAC RSS0680, a bifunctional compound designed for targeted protein degradation of kinases.

PROTACFLT3/CDKs degrader-1 (Compound C3) is an agent that degrades cyclin-dependent kinase (CDK2 with a DC50 of 18.73 nM) and FMS-like tyrosine kinase 3 (FLT3). It induces differentiation in HL-60 cells, achieving a 72.77% differentiation rate at 6.25 nM, and inhibits proliferation of acute myeloid leukemia (AML) cells, with an IC50 ranging from 2.9 to 37 nM. PROTACFLT3/CDKs degrader-1 demonstrates potential for improving the treatment of AML.

PROTACFLT3/GSPT1/IKZF1/3 degrader-1 is an FLT3 PROTAC degrader with DC50 = 1.2 nM. It functions as a molecular glue to degrade its brain substrates and exhibits antiproliferative activity against resistant acute myeloid leukemia (AML) cells, showing potential applications in AML research.

PROTACFLT3/JAK2/BRD4 Degrader-1 is a PROTAC degrader targeting FLT3, JAK2, and BRD4, with DC50 values of 5.23 nM, 0.678 nM, and 1.17 nM, respectively. It exhibits potent antiproliferative activity against MV4;11 cells (IC50= 0.79 nM) and FLT3-mutated Ba/F3 cells. Additionally, PROTACFLT3/JAK2/BRD4 Degrader-1 induces apoptosis in MV4;11 cells and demonstrates significant antitumor efficacy in an MV4;11 xenograft model established in NOD SCID mice. This compound is applicable for research in acute myeloid leukemia (AML).

PROTACFLT-3degrader 4 is an orally active CRBN-based FLT3-PROTAC degrader that efficiently induces the degradation of FLT3-ITD via the ubiquitin-proteasome system. It demonstrates high selectivity for FLT3-ITD mutant acute myeloid leukemia (AML) cells. [Blue: CRBN ligand, Black: linker; Pink: FLT3 inhibitor].

FLT3/CDKs ligand-1 (Compound 14) functions as a ligand for target proteins, promoting the degradation of Cyclin-Dependent Kinases (CDK) and FMS-like tyrosine kinase 3 (FLT3), thereby inhibiting the proliferation and survival of leukemia cells associated with FLT3/CDK. This compound is also used in the synthesis of PROTAC FLT3/CDKs Degrader-1.

Quizartinib (AC220) is an inhibitor of FLT3 (Kd: 1.6 nM) and demonstrates high selectivity for FLT3 when tested against a panel of 227 additional kinases.

PF15, a selective FLT3-ITD degrader, serves as a PROTAC (proteolysis targeting chimera) tethering ligands for FLT3 kinase and CRBN. It exhibits a degradation concentration 50 (DC50) of 76.7 nM and notably impedes the proliferation of FLT3-ITD-positive cells. PF15 also reduces phosphorylation levels of FLT3 and STAT5 and demonstrates efficacy in inhibiting tumor growth in mouse models, suggesting potential applications in leukemia research [1].

PF15 TFA, a PROTAC targeting FLT3 kinase and CRBN, exhibits selective degradation of FLT3-ITD with a DC50 of 76.7 nM. The compound potently suppresses proliferation in FLT3-ITD-positive cells, reduces phosphorylation levels of FLT3 and STAT5, and demonstrates inhibition of tumor growth in murine leukemia models [1].

Pomalidomide-C5-Dovitinib (compound 2) is a PROTAC linking Pomalidomide and Dovitinib via a CRBN connector, exhibiting potent antiproliferative activity in FLT3-ITD+ acute myeloid leukemia (AML) cells. It promotes ubiquitin-proteasome-dependent degradation of FLT3-ITD and KIT proteins, thereby inhibiting their downstream signaling pathways and presenting research potential in FLT3-ITD+ AML [1].

FLT3 ligand-2 serves as a ligand for the target protein in PROTAC. It is utilized for synthesizing PROTAC FLT-3 degrader 1.

E3 ligase Ligand 36 is an E3 ligase ligand that can be utilized for synthesizing PROTACs, such as PROTAC BRM/BRG1 degrader-1.

LWY713 is a PROTAC-based FLT3 degrader (DC50=0.64 nM) that selectively induces FLT3 degradation through a cereblon and proteasome-dependent mechanism. It inhibits cell proliferation and causes G0/G1 phase arrest and apoptosis (apoptosis) in MV4-11 cells. In MV4-11 xenograft models, LWY713 demonstrates significant in vivo antitumor activity. The E3 ligase ligand and linker consist of Lenalidomide-Glycolic acid, while the target protein ligand's active control is NaproxenGilteritinib.

MA191 is an FLT3 PROTAC degrader that effectively addresses FLT3 inhibitor resistance caused by the rebound activation of mitogen-activated kinases. It rapidly degrades FLT3-ITD via a mechanism involving VHL, Neddylation, and BIM, reducing FLT3-ITD levels prior to inducing apoptosis. Moreover, MA191 inhibits the proliferation of AML cells in zebrafish and is applicable for acute myeloid leukemia (AML) research.

BODIPY FL thalidomide is a fluorescent probe that binds human cereblon protein with high affinity, exhibiting a dissociation constant (Kd) of 3.6 nM [1].

Desmorpholinyl Quizartinib-PEG2-COOH is a compound featuring an FLT-3 ligand and a PEG-based PROTAC linker. It is employed in the synthesis of PROTAC FLT-3 degrader 1, which serves as a degrader for the FLT-3 internal tandem duplication (ITD) through PROTAC technology. The degrader exhibits an IC50 of 0.6 nM.