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.

Tubulin polymerization-IN-66 (Compound 13) inhibits colony formation and tubulin polymerization while also inducing apoptosis. It reduces cell viability in A549, A2780, SKOV3, and HCC827 cells, with IC50 values of 0.84, 0.38, 0.31, and 0.34 nM, respectively. Additionally, Tubulin polymerization-IN-66 is effective against the Paclitaxel-resistant A2780/T cancer cell line as well as its parent cell line, A2780.

CYP1B1-IN-9 is a highly selective and competitive CYP1B1 inhibitor, with IC50 values of 1.48 nM for CYP1B1, and greater than 100 μM and 80 μM for CYP1A1 and CYP1A2, respectively. This compound effectively inhibits the migration and invasion of A549/T cells, offers the potential to resensitize paclitaxel-resistant cells, and exhibits good metabolic stability and safety, as well as favorable pharmacokinetic properties. CYP1B1-IN-9 is applicable in research on tumor resistance.

pro-FTY is an anticancer prodrug of FTY720 and acts as a sphingosine-1-phosphate (S1P) inhibitor. It specifically inhibits S1P signaling in cancer cells via a drug delivery system (DDS) that reacts with acrolein. pro-FTY significantly reduces the survival of breast cancer cells, including multidrug-resistant cells and organoids resistant to Paclitaxel or Doxorubicin. Additionally, pro-FTY effectively suppresses tumor growth in xenograft mouse models of 4T1 cells or organoids while avoiding lymphopenia.

XIAP-CASP7 PPI-IN-1 is a reversible inhibitor of the XIAP:CASP7 interaction, effectively disrupting the connection between XIAP and CASP7. It selectively induces apoptosis in MCF-7 and caspase-3 low-expression (CASP3/DR) triple-negative breast cancer cells. The compound overcomes chemoresistance by down-regulating β-catenin and associated ABC transporters in paclitaxel-resistant MCF-7 cells. XIAP-CASP7 PPI-IN-1 is useful for breast cancer research.

Tubulin-IN-54 is a tubulin inhibitor exhibiting antiproliferative effects against various cancer cell lines. It disrupts microtubule assembly, leading to the breakdown of the microtubule network, inducing G2/M phase cell cycle arrest, and promoting apoptosis in cancer cells. Additionally, Tubulin-IN-54 demonstrates significant antitumor efficacy in mice with PC-3/TxR xenografts. It is applicable in studies of paclitaxel-resistant cancers, such as prostate cancer and melanoma.

BMS 275183 is a potent, orally active analogue of Paclitaxel. It stabilizes microtubules and exhibits antitumor activity in in vivo tumor models. BMS 275183 is also effective in vitro against Paclitaxel-resistant tumors, including those with tubulin mutations or overexpression of P-glycoprotein. It is applicable in cancer research, such as in non-small cell lung cancer (NSCLC) and prostate cancer studies.

SIK2/3-IN-2 (compound 12, compound I-200) is a potent SIK2/3 inhibitor, with IC50 values of 65 nM for SIK2 and 14 nM for SIK3. It also acts as an inhibitor of p21-activated kinase (PAK)1, with a Ki of 20.7 nM. SIK2/3-IN-2 is applicable in research on proliferative diseases and cancer, such as paclitaxel-resistant ovarian cancer.

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.