MOLM-13

BI-9321 trihydrochloride (BI9321 trihydrochloride) is a selective and potent NSD3-PWWP1 antagonist that downregulates Myc messenger RNA expression and reduces proliferation in MOLM-13 cells.

Serdemetan (JNJ-26854165) is an orally bioavailable HDM2 antagonist with potential antineoplastic activity.

Kevetrin hydrochloride (4-Isothioureidobutyronitrile hydrochloride) is a small molecule and activator of the tumor suppressor protein p53, with potential antineoplastic activity.

Atuveciclib (BAY 1143572) is a potent and highly selective PTEFb CDK9 inhibitor with an IC50 value of 13 nm for CDK9 CycT1 and a selectivity ratio of 100 for CDK2, with highly bioavailable and orally available advantages.

Alrizomadlin is an orally active MDM2 inhibitor. APG-115 shows significant dose-dependent inhibitory effects on TP53wt AML cell lines. The IC50 values ​​are 26.8 nM for MOLM-13 cells and 165.9 nM for MV-4-11 cells. , OCI-AML-3 cells 315.6 nM. Alrizomadlin blocks the interaction of MDM2 and p53 and induces cell cycle arrest and apoptosis in a p53-dependent manner.

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].

YL-5092 is an inhibitor of YT521-B homology (YTH) domain-containing protein 1 (YTHDC1). It inhibits acute myeloid leukemia cells with an IC50 of 0.28-2.87 μM. YL-5092 exhibits antitumor activity in xenograft mice models using MOLM-13 or U937 cells.

Compound 25h, also known as FLT3 HDAC-IN-2, is a dual inhibitor of FLT3 HDAC. It exhibits antiproliferative activity against MOLM-13 cells and is used in the study of acute myeloid leukemia.

PROTAC METTL3 degrader 1 (Compound KH12) is a VHL-based degrader of METTL3, demonstrating a DC50 of 220 nM in MOLM-13 cells. This compound inhibits the METTL3 14 complex with an IC50 of 341 nM and exhibits antiproliferative activity against AML cells.

PRMT5-IN-45 (compound 36) is a potent and selective inhibitor of PRMT5, exhibiting an IC50 value of 3 nM. This compound effectively reduces the levels of symmetrical dimethylarginine (sDMA) and inhibits the proliferation of the MOLM-13 cell line by inducing apoptosis and causing cell cycle arrest.

Nampt-IN-15 (Example 3) is a Nampt inhibitor that exhibits cytotoxic effects on various cell lines, including BxPC-3, HepG2, L540cy, and MOLM-13. The respective IC50 values for these cell lines are 38.5 nM, 8 nM, 8.5 nM, and 7 nM.

FLT3-ITD-IN-2 (Compound A1) is an inhibitor of the FLT3-ITD kinase, exhibiting an IC50 of 2.12 nM. It effectively suppresses the proliferation of the FLT3-dependent human AML cell line MOLM-13, with an IC50 of 25.65 nM. FLT3-ITD-IN-2 demonstrates antitumor activity against acute myeloid leukemia.

Antituberculosis agent-13 (Compound 11) demonstrates antituberculosis activity, effectively inhibiting both wild-type and mutant strains of Mycobacterium tuberculosis, with an IC50 range of 4-62.5 nM. Additionally, Antituberculosis agent-13 exhibits anti-leukemia properties, inhibiting MOLM-13 with an IC50 of 3.8 μM.

FW-1 is a type I inhibitor of FLT3, with an IC50 of approximately 1 μM. It exhibits cytotoxic effects in FLT3-mutant AML cells, causes cell cycle arrest at the G0 G1 phase, and induces apoptosis in MV4-11 and MOLM-13 cells.

FLT3-IN-28 (Compound 12y) is an orally active FLT3 inhibitor with antitumor properties. It selectively targets cancer cells with FLT3 internal tandem duplication (ITD) mutations, demonstrating IC50 values of 85, 290, 130, 65, and 220 nM against BaF3-FLT3-ITD, BaF3-TEL-VEGFR2, MV4-11, MOLM-13, and MOLM-14 cell lines, respectively. These lines include acute myeloid leukemia (AML) cells harboring FLT3-ITD mutations such as MV4-11 and MOLM-13 14. The compound also reduces phosphorylation levels of FLT3 and STAT5 in MOLM-13 cells, leading to cell cycle arrest and apoptosis. With an oral bioavailability of 19.2% in SD rats, FLT3-IN-28 extends survival in a dose-dependent manner in MOLM-13 xenografted NSG mouse models. It holds promise for research in FLT3-ITD-related cancer studies.

DP-15 acts as a degrader of GSPT1 and BRD4, with DC50 values of 5.25 nM and 0.48 nM, respectively. This compound exhibits antiproliferative activity in AML and NHL cells, showing IC50 values in the nanomolar range, induces G1 phase cell cycle arrest, and triggers apoptosis in MOLM13 cells. Additionally, DP-15 demonstrates anti-leukemic properties in the MOLM-13 xenograft mouse model. [Pink: ligand for target protein JQ-1 carboxylic acid; Black: linker; Blue: ligand for E3 ligaseCereblonThalidomide-5-OH]

DNMT1-IN-5 (Compound 55) is an inhibitor of DNMT, specifically targeting DNMT1 and DNMT3A, with IC50 values of 2.42 μM and 14.4 μM, respectively. It demonstrates antiproliferative effects across various cancer cell lines (TMD-8, DOHH2, MOLM-13, THP-1, RPIM-8226, and HCT116) with IC50 values ranging from 0.19 to 2.37 μM. The compound induces G2 M phase cell cycle arrest and apoptosis in TMD-8 and DOHH2 cells. Additionally, DNMT1-IN-5 exhibits antitumor efficacy in a TMD-8 xenograft mouse model.

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.

dBRD9 is a PROTAC. dBRD9 is a double-acting molecule, partially containing Bromodomain-containing protein 9 (BRD9), ligand that recruits the cereblon E3 ubiquitin ligase. Ligand that recruits the cereblon E3 ubiquitin ligase. dBRD9 can inhibit the degradation of BRD9 in MOLM-13 cells, and the IC50 is 104 nM.

dBRD9 HCl is a PROTAC composed of the BRD9 inhibitor BI 7273 conjugated to the cereblon E3 ligase ligand pomalidomide . dBRD9 HCl is a potent and selective degrader of BRD9 (IC50 = 56.6 nM in MOLM-13 cells). dBRD9 HCl does not degrade BRD4 or BRD7 at concentrations up to 5 μM. dBRD9 HCl displays antiproliferative effects in human AML cell lines.

UZH1 is a racemate of UZH1a and UZH1b. UZH1a is a potent and selective METTL3 inhibitor with an IC50 of 280 nM, while UZH1b (IC50=28 μM) is essentially inactive. UZH1 can be used for epitranscriptomic modulation of cellular processes, has antitumor activity, and serves as a chemical probe for studying METTL3[1].

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.

DHODH-IN-16 is an effective inhibitor of dihydroorotate dehydrogenase (DHODH, IC50 = 0.396 nM for human).

BPR1J-097, a new-type small molecule FLT-3 inhibitor(IC50=11±7 nM), is with great anti-tumor activities in vivo.