acute myeloid leukemia

PNU-159682, a metabolite of anthracycline neomycin, is a DNA topoisomerase II inhibitor with excellent cytotoxicity.

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.

PROTAC MPS1 Degrader 2 (Compound 15) is a potent degrader of monopolar spindle 1 (Mps1, TTK), AURKA, and AURKB with DC50 values of 42.0, 2.1, and 154.0 nM respectively. It is utilized in the research of acute myeloid leukemia.

PROTAC MPS1 degrader 1 (Compound 19) acts as a potent degrader of Monopolar spindle 1 (Mps1, TTK), AURKA, and AURKB, with DC50 values of 17.7, 108.7, and 570.3 nM respectively. It is utilized in the study of acute myeloid leukemia. (Pink: ligand for target protein; Black: linker; Blue: ligand for E3 ligase)

E3 Ligase Ligand-linker Conjugate 137 serves as both a linker and an E3 ligase ligand for PROTAC METTL3-14 degrader 1, employed in the study of acute myeloid leukemia.

JCS-1 is a potent DcpSPROTAC degrader. It non-covalently binds to DcpS via an RG3039-based warhead and recruits the E3 ligase VHL. JCS-1 facilitates the ubiquitination and degradation of DcpS at nanomolar concentrations, with a DC50 of 87 nM in MOLM-14 cells. This compound can be utilized in research on acute myeloid leukemia and other DcpS-dependent genetic disorders.

LYG-409 is an orally active GSPT1 degrader. It demonstrates exceptional in vivo anti-tumor activity against acute myeloid leukemia and prostate cancer, with tumor growth inhibition rates (TGI) of 94.34% and 104.49%, respectively. LYG-409 inhibits KG-1 cells by degrading GSPT1, with an IC50 of 9.50 nM and a DC50 of 7.87 nM in vitro.

P1D-34 is a Pin1 PROTAC degrader with a DC50 value of 177 nM. It downregulates Pin1 substrate proteins, including Cyclin D1, Rb, Mcl-1, Akt, and c-Myc. Additionally, P1D-34 exhibits antiproliferative activity across various acute myeloid leukemia (AML) cell lines and induces DNA damage and apoptosis by generating reactive oxygen species (ROS).

PROTACSMARCA2/4 degrader-38 is a SMARCA2/4 PROTAC degrader with DC50 values of 3.0 nM and 4.0 nM, respectively. It facilitates the ubiquitination and degradation of SMARCA2/4 and can block the G0/G1 phase of the cell cycle, leading to the induction of apoptosis. PROTACSMARCA2/4 degrader-38 is applicable in acute myeloid leukemia (AML) research.

(S)-dHTC1 is a molecular glue degrader specifically targeting the transcriptional coactivator ENL. It exhibits high affinity binding to E3 ligase only upon formation of the ENL:(S)-dHTC1 complex, with an IC50 of 93 nM. In MV4;11 cells, (S)-dHTC1 degrades ENL with a DC50 of 26 nM. This compound can be utilized for acute myeloid leukemia research.

CB039 is a selective degrader targeting RBM39 (RNA binding motif protein 39). It facilitates the formation of a ternary complex between RBM39 and the E3 ubiquitin ligase CUL4-DCAF15, resulting in the proteasomal degradation of RBM39. CB039 holds promise for research into cancers dependent on RBM39, such as acute myeloid leukemia (AML) and ovarian cancer.

DEG-35 is a CRBN-dependent bifunctional degrader targeting IKZF2 and CK1α, with DC50 values of 1.4 nM and 4.4 nM for CK1α and IKZF2, respectively. It activates the p53 apoptotic pathway and is applicable for research related to acute myeloid leukemia (AML).

ZS3-046 is a TAF1 PROTAC degrader that facilitates the ubiquitination and subsequent degradation of TAF1. It can activate p53 and induce apoptosis in acute myeloid leukemia (AML) cells. Additionally, ZS3-046 demonstrates anti-tumor efficacy in AML xenograft mouse models.

MS33 is a highly effective degrader of the WDR5 protein, exhibiting Kd values of 870 nM and 120 nM for VCB and WDR5, respectively. It induces degradation of WDR5 through an E3 ligase VHL-mediated and proteasome-dependent mechanism. MS33 holds promise for furthering research in the field of acute myeloid leukemia.

AK-2292 is a potent and selective STAT5 PROTAC degrader with a DC50 of 0.10 μM. It induces degradation of STAT5A B proteins in vitro and in vivo and can cause tumor regression in acute myeloid leukemia and chronic myeloid leukemia xenograft mouse models [1] [2].

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].

PROTAC ATR degrader-2 (Compound 8i) serves as a PROTAC degrader targeting ATR, effectively degrading it in acute myeloid leukemia (AML) cell lines MV-4-11 and MOLM-13, with DC50 values of 22.9 and 34.5 nM, respectively. This compound induces apoptosis and inhibits the proliferation of AML cells. Additionally, PROTAC ATR degrader-2 demonstrates favorable pharmacokinetic properties and potent antitumor activity in a mouse model of AML.

BMS-986397 is a casein kinase 1 α molecular gel degrading agent based on cereblon, which can promote rapid apoptosis and cell cycle arrest of TP53 wild-type acute myeloid leukemia cells.