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
Palomid 529 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human dermal microvascular endothelial cells (HDMEC)
20 µM
16 hours
Inhibited VEGF-A-driven Akt and downstream signaling pathways
Cancer Res. 2008 Nov 15;68(22):9551-7.
C6V10 glioma cells
20 µM
2 or 24 hours
Inhibited IGF-I-driven Akt and downstream signaling pathways, and inhibited mTOR association with rictor and raptor
Cancer Res. 2008 Nov 15;68(22):9551-7.
Human lung fibroblasts
10–20 µM
24 hours
P529 dose-dependently inhibited TGF-β-induced phosphorylation of S6K1 and 4E-BP1, with maximal inhibition occurring between 10–20 μM
J Cell Biochem. 2017 Aug;118(8):2241-2249.
PC-3 cells
2, 5, 7, 10 µM
48 hours
Evaluate the growth inhibitory effect of P529 on PC-3 cells. Results showed that P529 has a concentration-dependent growth inhibitory effect on PC-3 cells, with a GI50 of 5-7 μM.
Br J Cancer. 2009 Mar 24;100(6):932-40.
Leukemia and non-small cell lung cancer
2-34 µM (GI50)
48 hours
Evaluate the growth inhibitory effect of P529 on various tumor cell lines. Results showed that P529 has broad-spectrum growth inhibitory effects on multiple tumor cell lines.
Br J Cancer. 2009 Mar 24;100(6):932-40.
Melanoma, colon and ovarian cancers
6-24 µM (GI50)
48 hours
Evaluate the growth inhibitory effect of P529 on various tumor cell lines. Results showed that P530 has broad-spectrum growth inhibitory effects on multiple tumor cell lines.
Br J Cancer. 2009 Mar 24;100(6):932-40.
CNS, renal, breast, and prostate cancer
2-19 µM (GI50)
48 hours
Evaluate the growth inhibitory effect of P529 on various tumor cell lines. Results showed that P531 has broad-spectrum growth inhibitory effects on multiple tumor cell lines.
Br J Cancer. 2009 Mar 24;100(6):932-40.
Human umbilical vascular endothelial cells (HUVEC)
10 µM
6 hours
Induced endothelial cell apoptosis
Cancer Res. 2008 Nov 15;68(22):9551-7.
HROG10
7.5 µM
72 and 144 hours
In HROG10 cells, the combination of ADI and Palomid 529 reduced cell numbers by 70% after 144 hours.
Cancer Biol Ther. 2015;16(7):1047-55.
HROG05
7.5 µM
72 and 144 hours
In HROG05 cells, the combination of ADI and Palomid 529 reduced cell numbers by 70% after 144 hours.
Cancer Biol Ther. 2015;16(7):1047-55.
HROG02
7.5 µM
72 and 144 hours
In HROG02 cells, the combination of ADI and Palomid 529 reduced cell numbers by 50% after 72 hours and 70% after 144 hours.
Cancer Biol Ther. 2015;16(7):1047-55.
HUVECs
500 nM
96 hours
Evaluate the growth inhibitory effect of P529 on HUVECs. Results showed that P529 significantly inhibited VEGF-stimulated endothelial cell proliferation.
Br J Cancer. 2009 Mar 24;100(6):932-40.
Palomid 529 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
NMRI Foxn1nu mice
HROG05 xenograft model
Local administration
1 mg/kg
Twice a week for a total of 6 injections
Palomid 529 accelerated tumor growth, and the experiment had to be stopped at day 17 due to excessive tumor burden.
Cancer Biol Ther. 2015;16(7):1047-55.
Male athymic nude mice
PC-3 tumor model
Subcutaneous injection
20 mg/kg
Every 3 days for 4 weeks
Evaluate the antitumor effect of P529 alone or in combination with radiotherapy on PC-3 tumor growth. Results showed that P529 alone reduced tumor volume by 42.9%, and in combination with radiotherapy reduced tumor volume by 77.4%.
Br J Cancer. 2009 Mar 24;100(6):932-40.
Nude mice (nu/nu)
C6V10 glioma model
Intraperitoneal injection (i.p.)
200 mg/kg/2 days
Every 2 days for 21 days
Inhibited C6V10 glioma tumor growth, reduced tumor vascular density and glomeruloid vessel structures
Cancer Res. 2008 Nov 15;68(22):9551-7.
NOD.SCID/NCR mice
Brca1tr/tr MEFs-induced tumor model
Oral
40mg/kg
Once daily for 18 days
To investigate the inhibitory effect of Palomid 529 on Brca1-deficient tumor growth, results showed that P529 significantly suppressed tumor growth and reduced tumor size.
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