Ferrostatin-1 (Fer-1) is a potent and selective inhibitor of ferroptosis. Ferrostatin-1 potently inhibits Erastin-induced ferroptosis in HT-1080 cells with an EC50 of 60 nM. Ferrostatin-1 also exhibits antioxidant and antifungal activities.

CIL56 (CA3) is a small molecule that induces cellular ferroptosis through the production of iron-dependent reactive oxygen species (ROS). It also induces accumulation of long-chain saturated, monounsaturated, and polyunsaturated fatty acids in HT-1080 cells in vitro.HT-1080 cells lacking acetyl-CoA carboxylase 1 (ACC1), the rate-limiting enzyme in fatty acid synthesis, exhibit 5-fold resistance to CIL56 treatment, indicating ACC1 activity sensitizes cells to CIL56-induced cell death.

9,10-Dimethoxycanthin-6-one shows cytotoxic activity against a HT-1080 human fibrosarcoma cell line( IC50 = 5.0 microM).

Ferroptosis-IN-3 (Compound 25), a ferroptosis inhibitor, demonstrates potent activity by inhibiting RSL3-induced ferroptosis in HT-1080 cells (EC50: 8.6 nM). It exhibits radical scavenging abilities against DPPH and ABTS (EC50: 3.94 and 6.3 μM, respectively), and effectively reduces lipid peroxidation [1].

CC-3060 is a potent Cereblon modulator that facilitates the degradation of ZBTB16, exhibiting a DC50 of 0.47 nM in HT-1080 cells. It orchestrates ZBTB16 degradation by targeting discrete structural degrons within various zinc finger domains [1].

Calyxin B exhibits potent activity against human HT-1080 fibrosarcoma cells with an ED50 value of 0.69 microM. A methylated product of calyxin A and an epimeric mixture of Calyxin B, showed greatly reduced activity suggesting that phenolic hydroxyl groups

GSK321 is an effective and selective IDH1 mutation inhibitor, which can effectively inhibit the production of 2-HG in HT-1080 cells, and induce IDH1 mutant cells to differentiate into bone marrow at the level of leukemia blasts and more stem cells.

Paclitaxel octadecanedioate is a prodrug form of paclitaxel that is comprised of paclitaxel conjugated to 1,18-octadecanedioic acid.1 Unlike paclitaxel, it does not promote tubulin polymerization in vitro when used at a concentration of 10 μM. A 5:1 mixture of paclitaxel octadecanedioate:human serum albumin (HSA) is cytotoxic to HT-1080, PANC-1, and HT-29 cells (IC50s = 12, 2.48, and 8.62 nM, respectively). This mixture reduces tumor growth and increases survival in an HT-1080 mouse xenograft model in a dose-dependent manner. |1. Callmann, C.E., Leguyader, C.L.M., Burton, S.T., et al. Antitumor activity of 1,18-octadecanedioic acid-paclitaxel complexed with human serum albumin. J. Am. Chem. Soc. 141(30), 11765-11769 (2019).

PRLX-93936 is an analog of erastin that has antitumor activity. It inhibits the hypoxia-inducible factor 1 (HIF-1) signaling pathway under hypoxic conditions (IC50 = 0.09 μM in a cell-based reporter assay). PRLX-93936 (1 μM) also inhibits hypoxia-induced increases in HIF-1α expression in ME-180 cervical cancer cells. It inhibits the growth of HT-1080 fibrosarcoma, OVCAR-5 ovarian cancer, BJELR tumorigenic primary fibroblast, and PANC-1 pancreatic cancer cells with IC50 values of less than 100 nM. PRLX-93936 inhibits tumor growth in PANC-1 and HT-1080 xenograft models when administered at a dose of 50 mg/kg and induces tumor regression when administered at a dose of 100 mg/kg.

Ridaforolimus (AP23573) is a small molecule and non-prodrug analogue of the lipophilic macrolide antibiotic rapamycin with potential antitumor activity. Ridaforolimus binds to and inhibits the mammalian target of rapamycin (mTOR), which may result in cell cycle arrest and, consequently, the inhibition of tumor cell growth and proliferation. Upregulated in some tumors, mTOR is a serine/threonine kinase involved in regulating cellular proliferation, motility, and survival that is located downstream of the PI3K/Akt signaling pathway.

icFSP1, an inhibitor of ferroptosis suppressor protein 1 (FSP1), promotes condensation and phase separation of FSP1 in cellular environments at 2.5 µM concentration but does not affect FSP1's enzymatic function in cell-free assessments (IC50 = > 30 µM). This compound selectively induces ferroptosis in HT-1080 fibrosarcoma cells in a dose-dependent manner. Furthermore, in vivo studies show that icFSP1 administered at 50 mg/kg significantly reduces both the volume and weight of tumors in a B16/F10 murine melanoma model utilizing human FSP1-overexpressing, Gpx4-/-Fsp1-/- B16/F10 cells.

GPX4 24, a derivative of (1S,3R)-RSL3, acts as a potent inhibitor of glutathione peroxidase 4 (GPX4) through covalent binding in a concentration-dependent manner within 4T1 murine mammary carcinoma cells. This compound effectively induces ferroptosis in GPX4-dependent HT-1080 fibrosarcoma cells with an EC50 value of 0.16 µM. Additionally, at a dose of 200 mg/kg, GPX4 24 elevates malondialdehyde (MDA) levels in both kidney and plasma of mice, highlighting its impact on lipid peroxidation.

SRS11-92 (AA9) is a ferroptosis inhibitor and a derivative of ferrostatin-1

5'-Fluoroindirubinoxime (5'-FIO) is a potent FLT3 inhibitor( IC50 : 15 nM).

3-Methylcarbazole (NSC-10154) is an carbazole alkaloid compound with anticancer effects.

DAT-230 is a promising microtubule inhibitor that has great potential for the treatment of fibrosarcoma in vitro and in vivo. DAT-230 exhibited potent anti-proliferative activity against various cancer cells. DAT-230 -treatment in HT-1080 cells resulted in microtubule de-polymerization and G2/M phase arrest preceding apoptosis. Phosphor-cdc2 (thr14/tyr15) reduction, cyclin B1 accumulation and aberrant spindles denoted the cyclin B1-cdc2 complex active and M phase arrest in HT-1080 cells treated with DAT-230. Apoptosis induced by DAT-230 was related with the activation of caspase-9, caspase-3 and PARP cleavage, which were at the downstream of mitochondria.

Dihydroniloticin shows cytotoxic activity against a HT-1080 human fibrosarcoma cell line( IC50 = 8.2 microM).