temozolomide

Temozolomide (TMZ) is a DNA alkylating agent with blood-brain barrier permeability and oral activity. Temozolomide has antitumor activity and antiangiogenic activity, and also induces apoptosis and autophagy. Temozolomide is stable under acidic conditions and hydrolyzes under neutral or slightly alkaline conditions.

Temozolomide Acid (TMZA) is a metabolite of temozolomide (TMZ). Temozolomide processes anticancer activity in vitro. Temozolomide (TMZ) is an oral alkylating agent used to treat glioblastoma multiforme (GBM) and astrocytomas.

Levetiracetam (SIB-S1) is a relatively unique anticonvulsant that is typically used in combination with other antiepileptic medications for partial onset seizures. Levetiracetam has been linked to rare instances of serum aminotransferase and alkaline phosphatase elevations during treatment and to rare cases of clinically apparent drug induced liver disease.

STAT3-IN-31 (compound K2071), derived from STATtic, acts as an inhibitor of both STAT3 and mitotic processes. This compound interrupts mitotic progression and impacts the formation of the mitotic spindle. Additionally, STAT3-IN-31 hampers migration in glioblastoma cells, suppresses cellular proliferation within tumor spheroids, induces senescence in glioblastoma, and inhibits the growth of Temozolomide-resistant cells while reducing the secretion of the pro-inflammatory cytokine monocyte chemoattractant protein (MCP-1).

MTIC is the active metabolite of Temozolomide (TMZ) with anticancer and antitumor activity and is used in the study of melanoma.3'-Sialyllactose (3'-SL) sodium is a prebiotic with anti-inflammatory activity.

K34c is a potent and selective α5β1 integrin inhibitor (IC50 = 3.1 nM) that inhibits cell survival and migration, p53-dependent senescence induced by Temozolomide or Ellipticine, and promotes apoptosis in U87MG cells. Additionally, K34c prevents TGFβ-induced infiltration [in vivo] and reduces cell adhesion on fibronectin.

BRG1-IN-1 (Compound 11d) is a potent BRG1 inhibitor that surpasses PFI-3 in sensitizing GBM cells to the antiproliferative and cell death-inducing effects of Temozolomide in vitro, and enhances Temozolomide's inhibitory effect on subcutaneous GBM tumor growth[1].

PARP1-IN-10 (compound 12c) is a highly potent and non-cytotoxic PARP1 inhibitor with an in vitro IC50 value of 50.62 nM, effectively inducing cell cycle arrest at the G2 M phase and apoptosis, while significantly augmenting the cytotoxic effects of temozolomide (TMZ) [1].

NU1085 is a potent poly(ADP-ribose) polymerase (PARP) inhibitors have been developed that potentiate the cytotoxicity of ionizing radiation and anticancer drugs. The biological effects of NU1085 [Ki = 6 nM], in combination with temozolomide (TM) or topotecan (TP) have been studied in 12 human tumor cell lines (lung, colon, ovary, and breast cancer). Cells were treated with increasing concentrations of TM or TP + - NU1085 (10 microM) for 72 h.

IV-255 is a selective small molecule inhibitor of the BRG1 bromodomain, which heightens DNA damage when administered with Temozolomide and Bleomycin, curtails the invasiveness of GBM cells, and augments both Temozolomide-induced cell death and Temozolomide's apoptosis-inducing activity [1].

MAO A HSP90-IN-2 (compound 4-C), a dual inhibitor of HSP90 and MAO A, exhibits IC50 values of 0.016 μM for MAO A and 4.58 μM for HSP90. This compound enhances HSP70 expression, diminishes HER2 and phospho-Akt levels, downregulates IFN-γ-induced PD-L1 expression in GL26 cells, and demonstrates efficacy against Temozolomide-sensitive and -resistant GBM cells, colon cancer, leukemia, and non-small cell lung cancer, possibly impeding tumor immune evasion [1].

IV-275 is a dual inhibitor targeting the bromodomains of both BRG1 and BRM. This compound not only augments DNA damage when combined with Temozolomide and Bleomycin but also suppresses the invasiveness of GBM cells. Furthermore, IV-275 amplifies Temozolomide-induced cell death and its apoptosis-inducing activity [1].

HR68, a derivative of the peroxisome proliferator-activated receptor (PPAR) agonist fenofibric acid, serves as an anticancer agent. It effectively reduces the viability of LN-229 glioblastoma cells, with an IC50 value of 1.17 µM. Notably, HR68 is capable of crossing the blood-brain barrier in temozolomide-resistant orthotopic patient-derived xenograft (PDX) mouse models of glioblastoma.

Z4P, an IRE1 inhibitor with blood-brain barrier permeability (BBB) (IC50=1.13 μM), inhibits glioblastoma growth and recurrence in combination with Temozolomide.

PP5-IN-2, a selective and orally active inhibitor of protein phosphatase 5 (PP5), exhibits an IC 50 of 0.9 μM. This compound activates p53 and leads to the downregulation of cyclin D1 and MGMT, thereby inducing cell cycle arrest and reversing Temozolomide (TMZ) resistance in the U87 MG cell line. Additionally, PP5-IN-2 has demonstrated effective inhibition of tumor growth in the xenograft mouse model.