M-808 is a potent and efficacious covalent inhibitor, targeting the interaction between Menin and MLL. It demonstrates a high binding affinity with an IC50 value of 2.6 nM.
UZH1 is a racemate of UZH1a and UZH1b. UZH1a is a potent and selective METTL3 inhibitor, with an IC50 of 280 nM. UZH1b (IC50=28 μM) is essentially inactive. UZH1 can be used for epitranscriptomic modulation of cellular processes. UZH1 has antitumor activity. UZH1 also can be used as a chemical probe for studying METTL3[1]. UZH1a (2.5-160 μM; 72 h) inhibits the growth of MOLM-13, HEK293T, and U2Os cells, with IC50s of 11 μM, 67 μM, and 87 μM, respectively[1].UZH1b (2.5-160 μM; 72 h) inhibits the growth of MOLM-13, HEK293T, and U2Os cells, with IC50s of 78 μM, 79 μM, and 93 μM, respectively[1].UZH1a (2.5-100 μM; 16 h) reduces m6A methylation level in mRNA from cells in a dose-dependent manner (IC50=4.6 μM), while UZH1b is less active at concentrations up to 100 μM in MOLM-13 cells[1].UZH1a (40 μM; 16 h) reduces m6A methylation level in mRNA from MOLM-13, HEK293T, and U2Os cells[1].UZH1a (20 μM; 16 h) increases apoptosis and leads to cell cycle arrest in MOLM-13 cells[1]. [1]. Moroz-Omori EV, et, al. METTL3 inhibitors for epitranscriptomic modulation of cellular processes. bioRxiv. 2020 Oct 13.
Lenalidomide-C4-NH2 hydrochloride is a Cereblon ligand derived from Lenalidomide. It serves as a recruiting agent for the CRBN protein. The compound, known as PROTAC (Compound 24), can be formed by linking Lenalidomide-C4-NH2 hydrochloride to the ligand for the protein. It exhibits inhibitory effects with IC50s of 0.98 nM and 13.7 nM against the growth of RS4;11 and MOLM-13 acute leukemia cell lines, respectively[1].
M‑89 is a Highly Potent Inhibitor of the Menin-Mixed Lineage Leukemia (Menin-MLL) Protein−Protein Interaction (Kd = 1.4 nM; IC50 = 25nM). M-89 binds to menin with a Kd value of 1.4 nM and effectively engages cellular menin protein at low nanomolar concentrations. M-89 inhibits cell growth in the MV4;11 and MOLM-13 leukemia cell lines carrying MLL fusion with IC50 values of 25 and 55 nM, respectively, and demonstrates >100-fold selectivity over the HL-60 leukemia cell line lacking MLL fusion.
eSM156 is an effective FLT3 inhibitor. It has high antiproliferative activity against acute myeloid leukemia (AML) cells. eSM156 has IC50 (FLT3) = 1.4 nM; EC50 (MV4-11cells) = 150 nM; EC50 (MOLM-13 cells) = 40 nM.
BPR1J-340 is a potent and selective FLT3 inhibitor with potential anticancer activity. BPR1J-340 was identified as a novel potent FLT3 inhibitor by biochemical kinase activity (IC50 approximately 25 nM) and cellular proliferation (GC50 approximately 5 nM) assays. BPR1J-340 inhibited the phosphorylation of FLT3 and STAT5 and triggered apoptosis in FLT3-ITD(+) AML cells. The pharmacokinetic parameters of BPR1J-340 in rats were determined. BPR1J-340 also demonstrated pronounced tumor growth inhibition and regression in FLT3-ITD(+) AML murine xenograft models. The combination treatment of the HDAC inhibitor vorinostat (SAHA) with BPR1J-340 synergistically induced apoptosis via Mcl-1 down-regulation in MOLM-13 AML cells, indicating that the combination of selective FLT3 kinase inhibitors and HDAC inhibitors could exhibit clinical benefit in AML therapy.