paclitaxel resistant

NSC756093 potentially inhibits GBP1:PIM1 interaction. NSC756093 can be used in ovarian cancer studies.

KIF2C-IN-1 (Compound 7S9) is a selective and potent small molecule inhibitor of KIF2C. It stabilizes the interaction between KIF2C and microtubule proteins, preventing the depolymerization of polyglutamylated microtubules. KIF2C-IN-1 enhances the cytotoxicity of Paclitaxel in Paclitaxel-resistant triple-negative breast cancer (TNBC) cells and, when combined with Paclitaxel, significantly reduces tumor growth in mouse models.

P-gp inhibitor 5 is a potent P-glycoprotein (P-gp) inhibitor, reducing P-gp activity by a factor of 2.5 and 3.0 at 1.25 μM and 2.5 μM, respectively. It exhibits anti-proliferative effects on certain cancer cells and restores cellular sensitivity to Vincristine and Paclitaxel, reversing the multidrug resistant (MDR) phenotype of ABCB1 Flp-InTM-293 and KBvin.

WS-898 is a potent inhibitor of ABCB1 that reverses resistance to paclitaxel (PTX) in drug-resistant SW620 Ad300, KB-C2 and HEK293 ABCB1 cells with IC50 values of 5.0, 3.67 and 3.68 nM, respectively.

4SC-207 is a novel microtubule inhibitor , which shows strong anti-proliferative activity in a large panel of tumor cell lines with an average GI50 of 11 nM. In particular, 4SC-207 is active in multi-drug resistant cell lines, such as HCT-15 and ACHN, suggesting that it is a poor substrate for drug efflux pumps. 4SC-207 inhibits microtubule growth in vitro and in vivo and promotes, in a dose dependent manner, a mitotic delay arrest, followed by apoptosis or aberrant divisions due to chromosome alignment defects and formation of multi-polar spindles. Furthermore, preliminary data from preclinical studies suggest low propensity towards bone marrow toxicities at concentrations that inhibit tumor growth in paclitaxel-resistant xenograft models. 4SC-207 may be a potential anti-cancer agent.

DHFR-IN-9 (compound 8A), a dihydrofolate reductase (DHFR) inhibitor, impedes purine and thymidylate biosynthesis, pivotal in cell proliferation and growth. It demonstrates potency against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300 with an IC50 of 0.25 μg mL and exhibits anti-infective properties in mouse systemic and thigh infection models at doses of 2.5 mg kg and 5 mg kg administered intraperitoneally (ip). Furthermore, DHFR-IN-9 shows greater anticancer efficacy in a mouse breast cancer model compared to paclitaxel (Y-B0015), at a regimented dosage of 2.5 mg kg ip every three days [1].

S-(N-Methylsulfinylbutylthiocarbamoyl)-L-cysteine (SFN-Cys) is an isothiocyanate derivative, functioning as an active metabolite of sulforaphane, a class I and II histone deacetylase (HDAC) inhibitor, and anticancer agent. This compound is generated from sulforaphane through intermediates - DL-sulforaphane glutathione and sulforaphane cysteinylglycine - via the mercapturic acid pathway enzymes. At a concentration of 20 µM, SFN-Cys diminishes invasion and migration of U87MG and U373 MG glioblastoma cells as observed in wound healing and chamber assays. Furthermore, at 45 µM, it significantly lowers the expression of α-tubulin, βIII-tubulin, stathmin 1, and X-linked inhibitor of apoptosis (XIAP), and also reduces cell density in paclitaxel-resistant A549 lung cancer cells (A549/T). Additionally, when used at 30 µM, SFN-Cys prompts apoptosis and cell cycle arrest at the G2/M phase in U87MG and U373 MG cells.

Isotenulin inhibits the efflux function of P-glycoprotein (P-gp) by stimulating P-glycoprotein ATPase, helping to overcome multidrug resistance (MDR) in cancer cells. It exhibits cytotoxicity in multidrug-resistant cancer cells KB-vin and in sensitive cancer cells HeLaS3. Additionally, Isotenulin acts synergistically with Paclitaxel, Vinblastine, and Doxorubicin.