flt-3

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.

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.

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].

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.

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

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).

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].

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.

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.