mcf-10a

PK11000 is a p53 targeting compound, has anti-tumor activities through activation of unstable p53.

Defactinib (VS-6063) is a second-generation inhibitor of FAK that inhibits FAK phosphorylation at the Tyr397 site. Defactinib has potential antitumor activity.

4-Hydroxytamoxifen (ICI 79280) is the active metabolite of Tamoxifen, an estrogen receptor modulator (SERM) with selective and oral potency. 4-Hydroxytamoxifen has antitumor activity and may be used in breast cancer research.

VEGFR2-IN-1 is a selective and potent VEGFR2 inhibitor with antitumor activity that inhibits cell proliferation and migration and can be used in the study of breast cancer.

Heparan sulfate is a natural product, a linear polysaccharide. Heparan sulfate occurs as a proteoglycan (HSPG) that is tightly attached to cell surface or extracellular matrix proteins.

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.

Octamethylcyclotetrasiloxane promotes the growth of MCF-10A and MCF-10F cells under non-adherent conditions. It induces DNA damage upon prolonged high concentration exposure and inhibits the expression of DNA repair protein BRCA1. Additionally, octamethylcyclotetrasiloxane exhibits inherent estrogenic activity.

GLS-1-IN-1 (compound 1d) is a GLS-1 inhibitor effective against Hep G2, MCF 7, and MCF 10A cells.

PI3K-IN-28 is a potent PI3K inhibitor demonstrating high efficacy and lower toxicity in MCF-10a models. It exhibits half-maximal inhibitory concentration (IC50, μM) values of 5.8, 2.3, and 7.9. With a selectivity index (SI) of 39, PI3K-IN-28 emerges as a promising lead compound for the optimization of anticancer agents.

JMX0293, an O-alkylamino-tethered salicylamide derivative, demonstrates strong efficacy against the TNBC MDA-MB-231 cell line with an IC50 of 3.38 μM, while showing minimal toxicity towards the non-tumorigenic human breast epithelial cell line MCF-10A, where its IC50 exceeds 60 μM. It inhibits STAT3 phosphorylation, contributing to apoptosis in MDA-MB-231 cells, and significantly suppresses MDA-MB-231 xenograft tumor growth in vivo, all without notable toxicity.

NDNA4 (compound 17) is a selective Hsp90α inhibitor (IC50: 0.34 μM) with permanent charge and low membrane permeability. It demonstrates minimal cytotoxicity against Ovcar-8 and MCF-10A cell lines (IC50 >100 μM) and maintains hERG channel maturation without triggering a heat shock response or degrading Hsp90α-dependent client proteins [1].

NDNA3 (compound 14) selectively inhibits Hsp90α with an IC50 of 0.51 μM, demonstrating low membrane permeability and minimal toxicity to Ovcar-8 and MCF-10A cells, with IC50 values of 12.66 μM and 11.72 μM respectively. It stabilizes hERG channel maturation without eliciting a heat shock response or degrading Hsp90α-dependent client proteins [1].

ER degrader 7 (Compound 35t) is a selective degrader of both ERα and ERβ and functions as a tubulin polymerization inhibitor. It inhibits cell viability with IC50 values of 0.06 μM for MCF-7, 2.56 μM for T47D, 15.84 μM for MCF-10A, 1.59 μM for LCC2, 1.67 μM for T47D D538G, and 1.37 μM for T47D Y537S cells. Additionally, ER degrader 7 demonstrates efficacy in suppressing breast cancer tumor growth [1].

Compound Z10 (PKM2 activator 6) serves as both a PKM2 activator and a PDK1 inhibitor, exhibiting dissociation constants (K D ) of 121 μM and 19.6 μM, respectively. It promotes apoptosis in colorectal cells while suppressing their proliferation and migration, additionally inhibiting glycolysis. Compound Z10 demonstrates inhibitory effects on the proliferation of various cell lines, including DLD-1, HCT-8, HT-29, and MCF-10A, with half-maximal inhibitory concentrations (IC 50 ) of 10.04 μM, 2.16 μM, 3.57 μM, and 66.39 μM, as recorded in reference [1].

BRC4wt, an acetylated peptide originating from the BRC4 repeat within human BRCA2 (1521-1536), acts as an inhibitor of the BRCA2 and RAD51 protein-protein interaction. When linked to the cationic cell-penetrating peptide (Arg)9, it effectively shortens DNA replication tract lengths and diminishes the frequency of homologous repair of camptothecin-induced DNA damage in vitro. Additionally, BRC4wt enhances the efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib in inducing cell death in HeLa human cervical cancer and U2OS human osteosarcoma cells, albeit it does not affect non-cancerous hTERT RPE-1, MRC-5, or MCF-10A cells.

Fasnall, a fatty acid synthase (FASN) inhibitor, exhibits an IC50 of 3.71 μM against the human recombinant enzyme. It halts tritiated acetate incorporation into lipids (IC50= 5.84 μM), boosts ceramide levels, and triggers lipid droplet formation in BT474 HER2+ breast cancer cells. Demonstrating antiproliferative effects on various breast cancer cell lines, including non-tumorigenic MCF-10A and tumorigenic MCF-7, MDA-MB-468, BT474, and SK-BR-3, its efficacy is directly linked to FASN expression in vitro. In murine models of HER2+ breast cancer, particularly the MMTV-Neu model, Fasnall significantly reduces tumor volume and extends survival. Furthermore, it enhances the efficacy of carboplatin in vivo, bolstering the objective response rate of stable disease from 25% with carboplatin alone to 88% when paired with Fasnall.

PBE-AMF is a prodrug that activates H2O2 and exhibits anticancer activity. It impedes tumor proliferation by inhibiting DNA synthesis, reducing ATP levels, inducing cell death (apoptosis), and blocking the cell cycle. PBE-AMF effectively and selectively inhibits the proliferation of MDA-MB-231 cells (IC50=6.4 μM) while sparing non-cancerous MCF-10A cells.