mv4-11

GSK3685032 is a non-covalent and selective DNMT1 inhibitor(IC50 = 36 nM). The inhibitory effect is time-independent and reversible. GSK3685032 induces loss of DNA methylation and transcriptional activation and inhibits cancer cell growth.

Prexasertib (LY2606368) is an inhibitor of checkpoint kinase 1 (chk1) with potential antineoplastic activity.

Senexin C is a novel orally active and specific CDK8 19 inhibitor with potential anticancer activity.Senexin C is more metabolically stable and potent than Senexin B. Senexin C inhibits the growth of MV4-11 leukaemia cells.

CDK8-IN-12 is a selective, potent and orally active inhibitor of CDK8 (Ki: 14 nM) and is an anti-cancer agent. CDK8-IN-12 inhibits GSK-3α, GSK-3β and PCK-θ with Ki of 13 nM, 4 nM and 109 nM respectively. CDK8-IN-12 showed anti-proliferative activity against MV4-11 cells.

Adavosertib (MK-1775) is a small molecule inhibitor of the checkpoint kinase WEE1 (IC50: 5.2 nM). It hinders the G2 DNA damage checkpoint.

Alisertib (MLN 8237) is a specific Aurora A inhibitor (IC50: 1.2 nM). The selectivity of Alisertib(MLN 8237) is >200-fold higher for Aurora A than Aurora B.

SHP099 (SHP099 free base) free base is an effective, selective, orally bioavailable, and efficacious SHP2 inhibitor (IC50 =0.07 μM and p-ERK modulation in cells IC50 = 0.250 μM). SHP099 shows dose-dependent pathway inhibition and antitumor activity in xenograft models.

Entospletinib (GS-9973) (IC50= 7.7 nM)is a specific Syk inhibitor, which is orally bioavailable.

BRD4-IN-4 is a selective BRD4 inhibitor with an IC50 value of 6.83 μM for BRD4.BRD4-IN-4 selectively inhibits the proliferation of the MV4-11 cell line and arrests the cells in G1 phase.BRD4-IN-4 can be used to study MLL leukemias.

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.

SJ995973 is a highly potent bromodomain and extraterminal (BET) protein degrader and a BET PROTAC with potential anticancer activity.

CDK8-IN-14 (compound 12) effectively inhibits CDK8, demonstrating an IC50 of 39.2 nM, and exhibits potent anti-AML cell proliferation effects, with a GC50 value of 0.02±0.01μM in MOLM-13 cells and 0.03±0.01μM in MV4-11 cells [1].

HDAC CD13-IN-1 (Compound 12) is an inhibitor of both HDAC and CD13, with IC50 values of 0.34 μM for hCD13, 0.53 μM for porcine CD13, and 0.03, 0.06, and 0.02 μM for HDAC1, HDAC2, and HDAC3, respectively. This compound effectively suppresses proliferation and induces apoptosis in MV4-11, K562, Jeko-1, and HL60 cancer cells, with IC50 ranges of 0.25-2.04 μM, and demonstrates capabilities in hindering metastasis and invasion [1].

SJ44236 is a BET PROTAC degrader capable of degrading BRD2 (DC50 = 0.127 nM), BRD3, and BRD4. It shows cytotoxicity in MV4-11 and HD-MB03 cells with IC50 values of 0.12 nM and 0.92 nM, respectively. The compound downregulates c-Myc expression and upregulates p53 expression. In mice, SJ44236 demonstrates good oral bioavailability (45%). [Pink: ligand for target protein JQ-1 carboxylic acid; Black: linker; Blue: ligand for E3 ligaseCereblonE3ligaseLigand 54]

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.

HDAC-IN-88 (Compound HJ-9) is a potent inhibitor of HDAC, effectively targeting HDAC6, HDAC1, HDAC2, HDAC8, and HDAC3 with IC50 values of 0.226, 1.103, 2.308, 3.255, and 3.864 μM, respectively. This compound suppresses the proliferation of cancer cells HepG2, HCT116, and MV4-11 with IC50 values of 5.47, 9.78, and 0.38 μM, respectively. Additionally, it inhibits the migration of HCT116 cells, causes cell cycle arrest at the G0 G1 phase, and induces apoptosis and autophagy in MV4-11 cells. HDAC-IN-88 reduces ROS levels and mitochondrial membrane potential and demonstrates antimalarial activity by inhibiting Plasmodium falciparum 3D7 with an EC50 of 165 nM. Furthermore, HDAC-IN-88 exhibits anti-angiogenic properties.

Menin–KMT2A-IN-1 (Compound 20) is an inhibitor of menin–KMT2A, binding to menin with an IC50 of 8 nM, and disrupting the interaction between menin and lysine methyltransferase 2A (KMT2A). It inhibits hERG channels with an IC50 of 65 μM and suppresses MV4-11 cells with an IC50 of 74 nM. Furthermore, Menin–KMT2A-IN-1 exhibits favorable pharmacokinetic properties in CD-1 mice, with an oral bioavailability of 74%.

FTO-IN-14 (Compound F97) is an inhibitor of the RNA demethylase Fat mass and obesity-associated protein (FTO), with an IC50 of 0.45 μM. It modulates the expression of the ASB2, RARA, and MYC proteins. FTO-IN-14 demonstrates antiproliferative activity in AML cancer cells, with IC50 values of 0.7-5.5 μM against MOLM13, NB4, HEL, OCI-AML3, MV4-11, and MONOMAC6, and induces apoptosis in NB4 cells. Additionally, FTO-IN-14 exhibits antitumor activity in a mouse NB4 xenograft model.

PROTAC BRD4 Degrader-8 is a potent BRD4 inhibitor with IC50 values of 1.1 nM and 1.4 nM for BRD4 BD1 and BD2, respectively, effectively degrading the BRD4 protein in PC3 prostate cancer cells[1].

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

HDAC3-IN-5 (9c) is a selective inhibitor of HDAC3, exhibiting IC50 values of 4.2 nM for HDAC3, 1629 nM for HDAC2, and 298.2 nM for HDAC1. In vitro, it effectively induces apoptosis in MV4-11 cells and reduces the expression of anti-apoptotic proteins. The development of selective HDAC3 inhibitors like HDAC3-IN-5 (9c) could serve as potential lead compounds for reversing Venetoclax resistance.

FLT3-IN-22 (compound 22f) is a potent FLT3 inhibitor with IC50 values of 0.941 nM for FLT3 and 0.199 nM for the FLT3 D835Y mutant. It demonstrates significant antiproliferative effects against MV4-11 cells and Ba F3 cell lines expressing mutant FLT kinase variants, including FLT-D835Y and FLT3-F691L [1].

FLT3-IN-12 is a selective, potent, orally active FLT3 kinase inhibitor that acts on FLT3-WT (IC50: 1.48 nM) and FLT3-D835Y (IC50: 2.87 nM). FLT3-IN-12 is more selective than c-KIT (>1000-fold). FLT3-IN-12 showed significant anti-AML effects, with an IC50 value of 0.75 nM for MV4-11 cells.