molm-13

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

STM2457 is an inhibitor of the RNA methyltransferase METTL3 (IC50=16.9 nM) with selective and oral activity.STM2457 can be used in acute myeloid leukemia (AML) studies.

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.

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.

mTORinhibitor-26 (Compound HPT-11) is an mTOR inhibitor with an IC50 of 0.7 nM. It effectively inhibits the proliferation of AML cell lines Molm-13 and MV-4-11. mTORinhibitor-26 exhibits antitumor activity and demonstrates good metabolic stability, making it promising for research in the field of cancer.

Balomenib is an inhibitor of the menin-MLL interaction, effectively blocking the men1-MLL4-43 interaction with an IC50 of less than 0.075 μM. It inhibits cell growth in MV4-11 (CC50 < 0.1 μM), MOLM-13 (CC50 0.1~0.5 μM), and HEK293 (CC50 < 2 μM) cells. Balomenib also exhibits antitumor activity.

PROTACPIN1degrader-2 (1) is a PROTAC degrader of PIN1. The IC50 values of PROTACPIN1degrader-2 (1) against various cancer cells are as follows: 2248 nM for MV-4-11 cells, 3984 nM for MOLM-13 cells, and 3925 nM for HL-60 cells.

CDK9-IN-37 (Compound 24) is a CDK9 inhibitor with high selectivity, demonstrating an EC50 of 5.5 nM and minimal inhibition of other CDK subtypes. It shows significant antiproliferative activity against acute myeloid leukemia cells MOLM-13, with an IC50 of 0.034 μM. CDK9-IN-37 suppresses CDK9 signaling, reducing RNAP II CTD (Ser2) phosphorylation, downregulating the anti-apoptotic protein McI-1, inducing apoptosis, and causing cell cycle arrest at the G2/M phase. This compound is applicable in the research of acute myeloid leukemia (AML).

HDSI-18 is an orally active selective inhibitor of HDAC6 with an IC50 of 1.6 nM. It exhibits cytotoxic effects against K562, MV4-11, MOLM-13, THP-1, and Jurkat cells with IC50 values of 0.48, 0.58, 0.91, 1.79, and 4.31 μM, respectively. HDSI-18 can activate Caspase-3, induce mitochondrial depolarization, and trigger apoptosis (Apoptosis), demonstrating antitumor activity.

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

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.