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.

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.

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.

BRG1-IN-1 (Compound 11d) is a potent BRG1 inhibitor with better efficacy than PFI-3 in sensitizing GBM cells to the antiproliferative and cell death inducing effects of Temozolomide in vitro. BRG1-IN-1 enhances the inhibitor effect of Temozolomide on the subcutaneous GBM tumors growth[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 not only enhances HSP70 expression but also diminishes HER2 and phospho-Akt levels, and downregulates IFN-γ-induced PD-L1 expression in GL26 cells. Demonstrating efficacy against Temozolomide-sensitive and -resistant GBM cells, colon cancer, leukemia, non-small cell lung cancer, and other malignancies, MAO A/HSP90-IN-2 may also impede tumor immune evasion [1].

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

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). K34c inhibits cell survival and migration, inhibits p53-dependent senescence induced by Temozolomide or Ellipticine and promotes apoptosis in U87MG cells. K34c also prevents TGFβ-induced infiltrationin vivoand reduces cell adhesion on fibronectin.

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