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.

JSH-23 is an NF-κB inhibitor that inhibits NF-κB transcriptional activity (IC₅₀=7.1 μM) but does not affect IκBα degradation. JSH-23 is an antioxidant with anti-inflammatory activity.

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.

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.

Alvameline (Lu25-109) is a partial M1 agonist and an M2/M3 antagonist.

Alvameline maleate is used as a Partial M1 Agonist and M2/M3 Antagonist.

Alvameline Tartrate, a muscarinic M1 receptor agonist and M2/M3 receptor antagonist, is used potentially for treatment of urinary incontinence.

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.

Dopamine D4 receptor ligand 3 (Compound 16) functions as a dopamine D4 receptor (D4R) antagonist with a pKi of 8.86. In HEK-293T cells, it shows pIC₅₀ values of 5.78, 5.55, and 6.17 for Go, Gi, and βArr2 sensors, respectively. This compound inhibits the activity of human glioma cell lines U87 MG, T98G, and U251 MG, and it induces ROS production and mitochondrial dysfunction in these glioma cells.

OLIG2-IN-1 is a potent and selective inhibitor of the oligodendrocyte transcription factor 2 (OLIG2). It directly and dose-dependently reduces nuclear OLIG2 levels with an IC₅₀ of 0.88 μM. In U87 and U251 cells, OLIG2-IN-1 exhibits significant antiproliferative activity with IC₅₀ values of 7.02 μM and 6.43 μM, respectively. OLIG2-IN-1 is applicable in cancer research, particularly for studying glioblastoma multiforme.

Arg-PEG1-Tαsyn is a PROTAC degrader targeting α-synuclein (α-syn), with a DC50 of 0.28 μM in U251 cells. This compound utilizes arginine (Arg) as the E3 ligase ligand and a benzothiazole-aniline variant as the warhead for α-syn targeting. It effectively degrades both wild-type α-syn and its A53T mutant in mammalian cells. In vitro, Arg-PEG1-Tαsyn significantly reduces α-syn aggregation via the E3 ubiquitin ligase UBR1. In vivo, it demonstrates good safety and significantly improves dopaminergic neuron damage and motor dysfunction. Arg-PEG1-Tαsyn is useful in Parkinson's disease research.

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.

MSB-0254 is a human monoclonal antibody (mAb) that targets VEGFR2/KDR/CD309. It inhibits the invasion, migration, and vasculogenic mimicry (VM) formation of U251 and primary glioma cells. Additionally, MSB-0254 suppresses the growth of U251 and GL261 cell-transplanted tumors. It reduces the expression of CD34, VEGFR2, Ki67, MMP2, MMP9, and CD34/PAS. MSB-0254 is applicable to research on advanced solid tumors.