Palomid 529 (P529) inhibits endothelial cell proliferation driven by VEGF (IC50, 20 nM) and bFGF (IC50, 30 nM) and induces endothelial cell apoptosis[1]. Palomid 529 (RES-529) serves as a PI3K/AKT/mTOR pathway inhibitor, disrupting the pathway by dissociating both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). This inhibitor reduces mTORC1/mTORC2 activity across various cancer cell lines, evidenced by decreased phosphorylation of ribosomal protein S6, 4E-BP1, and AKT, which leads to cell growth inhibition and cell death, typically within the 5-15 μM range. At a concentration of 10 μM, Palomid 529 diminishes the binding of 0.5 nM [3H]estradiol to estrogen receptor (ER)α and ERβ by 3% or less. It inhibits HUVEC cell proliferation induced by VEGF and β fibroblast growth factor, with IC50 values of approximately 10 and 30 nM, respectively. Palomid 529 also induces a four-fold increase in apoptosis in HUVEC cells, as indicated by DNA fragmentation. In various cancer cell lines from the National Cancer Institute-60 (NCI-60) tumor panel, Palomid 529 demonstrates growth inhibition with IC50 values ranging from 5-15 μM for central nervous system cancer cells and 5-30 μM for prostate cancer cells[2]. Palomid 529 (P529) leads to a dose- and time-dependent reduction in Akt activity in PC3, LnCaP, and 22rv1 cells, as indicated by decreased phosphorylation of Akt (Ser473). This effect is consistent across all PCa cells with enzymatic IC50s around 0.2 μM. Palomid 529 variably inhibits the proliferation of neoplastic cells (IC50s ranging from 5 to 28 μM), while having minimal impact on non-neoplastic BPH1 and EPN cells. Additionally, treatment with Palomid 529 causes a concentration-dependent decrease in the viability and proliferation
体内研究
Palomid 529 (200 mg/kg/2d) inhibits tumor growth in C6V10 glioma in nude mice following intraperitoneal dosing, also reducing AktS473 but not AktT308 signaling within the tumor lysates[1].
Palomid 529 has demonstrated antitumor activity in various mouse models, including those for glioblastoma, prostate, and breast cancer. In a C6V10 glioblastoma subcutaneous xenograft model, pretreatment with Palomid 529 (200 mg/kg/2 days, intraperitoneal) significantly reduces tumor volume. Similarly, treatment with micronized Palomid 529 three days post-tumor cell injection significantly inhibits tumor growth in a human U87 glioblastoma model[2].
Palomid 529 reduces tumor growth in a dose-dependent manner in PC3 and 22rv1 xenografts, with tumor mass reductions of 10, 47.6, and 59.3% in PC3 xenografts and 9, 38.7, and 51.5% in 22rv1 xenografts at doses of 50, 100, and 200 mg/kg, respectively[3].
体外研究
Palomid 529 (P529) inhibits endothelial cell proliferation driven by VEGF (IC50, 20 nM) and bFGF (IC50, 30 nM) and induces endothelial cell apoptosis[1].
Palomid 529 (RES-529) serves as a PI3K/AKT/mTOR pathway inhibitor, disrupting the pathway by dissociating both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). This inhibitor reduces mTORC1/mTORC2 activity across various cancer cell lines, evidenced by decreased phosphorylation of ribosomal protein S6, 4E-BP1, and AKT, which leads to cell growth inhibition and cell death, typically within the 5-15 μM range. At a concentration of 10 μM, Palomid 529 diminishes the binding of 0.5 nM [3H]estradiol to estrogen receptor (ER)α and ERβ by 3% or less. It inhibits HUVEC cell proliferation induced by VEGF and β fibroblast growth factor, with IC50 values of approximately 10 and 30 nM, respectively. Palomid 529 also induces a four-fold increase in apoptosis in HUVEC cells, as indicated by DNA fragmentation. In various cancer cell lines from the National Cancer Institute-60 (NCI-60) tumor panel, Palomid 529 demonstrates growth inhibition with IC50 values ranging from 5-15 μM for central nervous system cancer cells and 5-30 μM for prostate cancer cells[2].
Palomid 529 (P529) leads to a dose- and time-dependent reduction in Akt activity in PC3, LnCaP, and 22rv1 cells, as indicated by decreased phosphorylation of Akt (Ser473). This effect is consistent across all PCa cells with enzymatic IC50s around 0.2 μM. Palomid 529 variably inhibits the proliferation of neoplastic cells (IC50s ranging from 5 to 28 μM), while having minimal impact on non-neoplastic BPH1 and EPN cells. Additionally, treatment with Palomid 529 causes a concentration-dependent decrease in the viability and proliferation
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