Table 2 Treatments against FOXM1 in glioma

Bortezomib [109]

High-grade glioma (HGG)

Proteasome inhibtor

–

NCT00611325/NCT00990652/NCT00006773/NCT00994500/NCT03643549/NCT00998010/NCT01435395/NCT00641706/NCT00544284/NCT00108069

Approved for Multiple Myeloma

FOXM1–Survivin

In vivo/in vitro

• ↓Cell viability, spheroid growth, colony formation, and stemness of glioma cells

• ↑TMZ efficacy

OTSSP167 [115]

GBM

MELK inhibitor

100 to 200 nM

–

–

MELK/AKT/FOXM1

Reduce AKT phosphorylation

In vivo/in vitro

• ↓Proliferation, migration, and Invasion

• ↑Cell cycle arrest in the G2/M phase

• ↓Neurosphere formation in GSCs

C646 [116]

Glioma stem cells in GBM

Small molecule inhibitor of CBP

–

–

–

SATB2/CBP/FOXM1

In vivo/in vitro

• C646 inhibits SATB2/CBP transcriptional activity and inhibits tumor proliferation

• SATB2 and CBP are preferentially expressed by GSCs

• SATB2 recruits CBP to activate FOXM1 transcription

Fimepinostat (CUDC-907) [43]

Pediatric HGG

HDAC and PI3K inhibitor

–

NCT02909777/NCT03893487

–

decreased phosphorylation of AKT

In vivo/in vitro

• Induces cytotoxicity and synergism with radiotherapy

• ↑DNA damage

• ↓Expression of critical DDR genes through an NFκB- and FOXM1-mediated pathway

Siomycin A [28]

GSCs and GBM

Antibiotic

–

–

–

Abrogates FOXM1-MELK Interaction

In vivo/in vitro

• Overexpression of FOXM1 with MELK, but not FOXM1 or MELK alone, rescued the Siomycin A-induced G2/M arrest of GBM30 GSCs

• Co-treatment with TMZ and Sio A is more effective than using TMZ alone

Plumbagin [117, 118]

Glioma

Natural quinonoid

2.83 μM [117] and

3.22 μM[118]

–

–

Inhibits transcriptional activity of FOXM1

↓cyclin D1, Cdc25B, surviving

↑p21CIP1 and p27KIP1

In vitro

• ↓Viability, proliferation, migration, and invasion of glioma cells

• ↑ Cell cycle arrest, apoptosis

3-O-acetyl-11-keto-β-boswellic acid(AKBA) [119]

GBM

Natural product

18.69 μM to 31.61 μM (different per cell lines)

–

–

p21/FOXM1/cyclin B1

In vivo/in vitro

• ↓Cell proliferation, DNA synthesis, migration, invasion, and colony formation

• AKBA arrested the cell cycle at mitosis by regulating aurora B/TOP2A

Sophoridine [120]

Glioma

Natural product

5.3 mg/ml

–

–

Inhibits the transcriptional activity of FOXM1

In vitro

• ↓ Growth

• ↑Apoptosis and arrested

• Induced ROS production

• Inhibited ubiquitin–proteasome

ZR30 (Human fibulin-3 protein variant) [121]

GBM

synthesized protein

–

–

–

In vivo downregulation of FOXM1

and

IGFBP3 and SEMA3B

EGFR/NOTCH/AKT

In vivo/in vitro

• Exerts tumor suppressive effect via downregulating membrane receptors (EGFR, NOTCH1) and their downstream AKT-signaling, MMP2, and FoxM1

Thiostrepton [96]

Glioma

Natural product

–

–

–

Inhibits FoxM1-RFC5

In vivo/in vitro

• ↓TMZ resistance and proliferation

Silibinin [122]

GBM

Natural product

–

–

–

Inhibits PI3K/Akt signaling

In vitro

• ↓Proliferation

• ↑Cell apoptosis

Curcumin [66]

GBM

Natural product

15 µM and 31 uM for the U87 and T98G

NCT05768919/NCT01712542

–

Inhibits GLI1 as an upstream regulator of FOXM1

In vivo/in vitro

• ↓ Proliferation and migration

• ↑G2/M Arrest and apoptosis

• ↑ Survival period

Chalcone 9X [123]

GBM

Natural product

–

–

–

repressed the protein levels of FOXM1

In vivo/in vitro

• ↓Cell proliferation, apoptosis, and migration

Diferuloylsecoisolariciresinol (DFS) [124]

GBM

Natural product

–

-

-

inhibited the binding of FOXM1 and β-catenin

In vivo/in vitro

• ↓Stemness and invasiveness

• ↓Viability and ATP levels

• ↑ Cell cycle arrest

MeICT [125]

GBM

toxin isolated from scorpion

3.8 μM

–

–

–

In vivo/in vitro

• ↓Cell proliferation

Ena15 [62]

GBM

2OG-like ALKBH5 inhibitors

18.3 ± 1.8

–

–

Increases m6A modification of FOXM1

In vitro

• ↓Cell proliferation and cell population in the synthesis phase of the cell cycle

• ↑m6A RNA level of FOXM1

Ena21 [62]

15.7 ± 1.0

–

–