u251

Topotecan (NSC-609669) is a Topoisomerase I inhibitor,and is an antineoplastic agent used to treat ovarian cancer that works by inhibiting DNA topoisomerases.

Sertindole (Lu 23-174) is an atypical antipsychotic that binds to dopamine D2 receptors and serotonin (5-HT) receptor subtypes 5-HT1D, 5-HT2A, and 5-HT2C, with Kds of 2.7, 20, 0.14, and 6 nM, respectively.

Anisomycin is an antibiotic and protein synthesis inhibitor produced by Streptomyces griseolus. It is also a classic activator of p38 MAPK and JNK. By inhibiting protein synthesis, anisomycin induces cellular stress, which activates upstream kinases and subsequently leads to the phosphorylation and activation of p38 MAPK and JNK.

Echinomycin (Quinomycin A) is an antitumor antibiotic secondary metabolite isolated from Streptomyces, a quinoxaline antibiotic, a DNA doubly intercalating peptide, and inhibits hypoxia-inducible factor-1 (HIF-1) DNA binding activity. Echinomycin has potential anticancer activity and can be used to study triple-negative breast cancer.

FAK-IN-24 (Compound 9f) is a potent FAK inhibitor with an IC50 of 0.815 nM. It induces DNA damage and apoptosis, and exhibits activity against glioblastoma. FAK-IN-24 effectively inhibits proliferation of glioblastoma cell lines U87-MG (IC50= 15 nM) and U251 (IC50= 20 nM), and suppresses tumor growth in U87-MG xenograft models.

CAIX CAXII-IN-4 (Compound 7h) is an inhibitor of carbonic anhydrase (CA) that binds to CAIX, CA XII, and CAII with Ki values of 1.324 μM, 0.435 μM, and 3.035 μM, respectively. This compound exhibits broad-spectrum anti-tumor activity and inhibits the proliferation of central nervous system tumor cells U251, with a GI50 of 0.361 μM.

Lanuginosine, an aporphine alkaloid, exhibits cytotoxicity against U251.

Cyclopamine-KAAD is a potent inhibitor of hedgehog signaling with an IC50 value of 20 nM in a Shh-LIGHT2 assay. It blocks binding of BODIPY-cyclopamine to cells expressing Smoothened (Smo) in a dose-dependent manner. Cyclopamine-KAAD is cell-permeable and binds to SmoA1 to promote its exit from the endoplasmic reticulum. It inhibits the invasion and migration (45.9 and 43.3% inhibition, respectively) of Bel-7402 hepatocarcinoma cells and decreases the expression of nuclear glioma-associated oncogene 1 (Gli1) and cytosolic MMP-9, pERK1, and pERK2 proteins in a dose-dependent manner. Cyclopamine-KAAD also increases TRAIL-mediated cell death in NCH82 and NCH89 human glioblastoma cultures and upregulates expression of the death receptors DR4 and DR5 in LN229 and U251 glioma cells.

Arecaidine propargyl ester is an agonist of M2muscarinic acetylcholine receptors (mAChRs).1It selectively binds to M2over M1, M3, M4, and M5mAChRs in CHO cells expressing the human receptors (Kis = 0.0871, 1.23, 0.851, 0.977, and 0.933 μM, respectively). Arecaidine propargyl ester induces contractions in isolated guinea pig atrium (pD2= 8.67). It induces apoptosis and the production of reactive oxygen species (ROS) in U87 and U251 glioblastoma cells when used at a concentration of 100 μM.2Arecaidine propargyl ester decreases mean arterial blood pressure in normotensive cats (ED25= 1.9 nmol kg).3It is toxic to house flies (Musca) when administered at a dose of 75 μg fly.4 1.Scapecchi, S., Matucci, R., Bellucci, C., et al.Highly chiral muscarinic ligands: the discovery of (2S,2'R,3'S,5'R)-1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide methyl iodide, a potent, functionally selective, M2 partial agonistJ. Med. Chem.49(6)1925-1931(2006) 2.Di Bari, M., Tombolillo, B., Conte, C., et al.Cytotoxic and genotoxic effects mediated by M2 muscarinic receptor activation in human glioblastoma cellsNeurochem. Int.90261-270(2015) 3.Porsius, A.J., and Van Zwieten, P.A.Central action of some cholinergic drugs (arecaidine esters) and nicotine on blood pressure and heart rate of catsProg. Brain Res.47131-135(1977) 4.Honda, H., Tomizawa, M., and Casida, J.E.Insect muscarinic acetylcholine receptor: Pharmacological and toxicological profiles of antagonists and agonistsJ. Agric. Food Chem.55(6)2276-2281(2007)

Linoleic acid is an essential fatty acid and one of the most abundant polyunsaturated fatty acids in the western diet. Pyrrolidine Linoleamide is a derivative of the amide of linoleic acid that shows potent antiproliferative activity against an array of cancer cell lines, including human glioma U251 cells. It is greater than 4-fold more effective against cancer cells than non-cancer cells.

Ricinoleic acid is a naturally occurring 12-hydroxy fatty acid. It constitutes about 90% of the fatty acids in castor oil. Pyrrolidine Ricinoleamide is a derivative of the amide of ricinoleic acid that shows potent antiproliferative activity against an array of cancer cell lines, including human glioma U251 cells.

(S)-α-Methylbenzyl ricinoleamide is a fatty acid amide derived from ricinoleic acid and methyl benzylamine. It demonstrates potent growth inhibition of glioma (U251), breast (MCF-7), ovarian (NCI-ADR/RES and OVCAR-3), kidney (786-0), non-small cell lung (NCI-H460), and prostate (PC-3) cancer cells with a mean GI50 value of 6.9 μM.

KY386 is a potent and selective DHX33 helicase inhibitor with an IC50 value of 19 nM. It demonstrates significant anti-cancer activity in DHX33-overexpressing U251-MG cell strain, achieving an IC50 of 20 nM, and exhibits moderate metabolic stability [1].

10m ZS44, a blood-brain barrier-permeable Glioblastoma (GBM) inhibitor, significantly suppresses tumor growth in mouse xenograft models and induces apoptosis through activation of the SIRT1 p53-mediated pathway, thereby reducing U251 cell proliferation [1].

S7, a peptide antagonist of the IL-6 receptor, concentration-dependently inhibits IL-6 binding to its receptor. At 50 µM, S7 suppresses IL-6-triggered elevations in VEGF levels within C-33 A cervical cancer cells and RPMI-8226 B cell lymphocytes. It significantly reduces tumor volume in a C-33 A cervical cancer mouse xenograft model with IL-6 overexpression, following a dosage regimen of 50 mg/kg bi-daily. Moreover, when linked to cysteine on lipid nanoparticles (LNPs) encapsulating doxorubicin, S7 enhances glioma targeting and improves survival rates in a U251 glioblastoma mouse xenograft model.

UniPR1454 targets the EphA2 receptor and inhibits the interaction between EphA2 and ephrin A1, with an IC50 of 2.6 μM. Furthermore, UniPR1454 suppresses the proliferation of glioblastoma U251 cells.