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| 5mg |
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Purity: ≥98%
Palomid 529 (also called P529, SG00-529), developed by Paloma Pharmaceuticals, is a novel and potent inhibitor of mTOR (mammalian target of rapamycin) with potential antitumor activity.
| Targets |
TORC1; TORC2
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|---|---|
| ln Vitro |
Palomid 529 inhibits proliferation and increases apoptosis of endothelial cells. Palomid 529 has an IC50 of 20 nM for VEGF-driven inhibition and 30 nM for bFGF-driven inhibition of endothelial cell proliferation. The ability of palomid 529 to cause endothelial cell apoptosis is still present. Palomid 529 lessens the phosphorylation of pAktS473, pGSK3S9, and pS6 caused by VEGF-A. However, Palomid 529 does not inhibit pAktS473 as effectively as pAktT308 or phosphorylated mitogen-activated protein kinase (pMAPK). [1] Palomid 529 enhances the organization and structure of newly formed blood vessels in addition to reducing the proliferative response in the ischemic retina.[1] Palomid 529 enhances the structure and organization of the developing blood vessels in addition to reducing the proliferative response in the ischemic retina. [1] The NCI-60 cell lines panel demonstrates Palomid 529's potent antiproliferative activity, with a growth inhibitory 50 (GI50) of only <35 μM. The antiproliferative effect of radiation on prostate cancer cells (PC-3) is also markedly improved by Palomid 529. On PC-3 cells, palomid 529 causes a growth inhibition that is dependent on concentration. 30 and 60% of growth were inhibited by doses of 2 and 7μM, respectively. The Bcl-2/Bax ratio in PC-3 is decreased by palomid 529, which also inhibits radiation-induced p-Akt activation. In addition to preventing Id-1 and VEGF overexpression brought on by radiation, palomid 529 also inhibits MMP-2 and MMP-9 overexpression brought on by radiation.[2]
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| ln Vivo |
Palomid 529 treatment results in a dose-dependent inhibition of Ad-VEGF-A-driven angiogenesis. Palomid 529's i.p. dose-dependent inhibition of C6V10 glioma tumor growth in nude mice. Palomid 529 reduces the signaling of AktS473 but not AktT308. Palomid 529's i.p. dose-dependent inhibition of C6V10 glioma tumor growth in nude mice. Palomid 529 reduces the signaling of AktS473 but not AktT308. Palomid 529 reduces vascular permeability, angiogenesis, and tumor growth. [1] Palomid 529 treatment slowed the growth of tumors in PC-3 tumor-bearing mice by 57.1% in comparison to untreated mice.[2] Palomid 529 is a potent suppressor of Müller cell proliferation, glial scar formation, and photoreceptor cell death in a rabbit model of retinal detachment (RD). [3] By inhibiting both Akt and mTOR signaling, palomid 529 significantly slows the growth of Brca1-deficient tumors in mice. [4]
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| Enzyme Assay |
The proteins are produced with rabbit reticulocyte lysates. In parallel reactions where [35S]methionine is incorporated into the receptor, followed by gel electrophoresis and exposure to film, expression is monitored and the amount of template used in each reaction is empirically determined. In 100 mL final volumes of TEG buffer [10 mM Tris (pH 7.5), 1.5 mM EDTA, 10% glycerol], binding reactions between Palomid 529 and estrogen receptors (ER) are conducted. Each binding reaction involves the use of 5 μL of in vitro transcribed-translated receptor in the presence of 0.5 nM [3H]estradiol (E2). Palomid 529 is routinely diluted in ethanol and tested from 10−11 to 10−6M. By adding 200 mL of dextran-coated charcoal, bound E2 is measured after the reactions have been incubated at 4 °C overnight. In order to determine the cpm by liquid scintillation counting, the tubes are rotated for 15 minutes at 4 °C, centrifuged for 10 minutes, and 150 mL of the supernatant are added. By only using the ethanol vehicle to compete with bound E2, the maximum binding is determined. Each experiment uses 5 mL of unprogrammed rabbit reticulocyte lysate as background controls. This amount, which typically represents 10% to 15% of the maximum counts, is taken out of all values. Calculated Ki values are plotted on the data. At least three separate experiments are carried out.
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| Cell Assay |
The cells used are human umbilical vascular endothelial cells (HUVEC). The HUVECs are seeded in 96-well plates at a density of 1,000 cells per well in complete medium to perform the proliferation assay. After 24-hour plating, the cells are starved in 0.5% serum for 24 hours before being treated with Palomid 529 in complete medium containing 10 ng/mL basic fibroblast growth factor (bFGF) or VEGF. A colorimetric method is used to determine the cell number after 48 hours. As a percentage of the maximum bFGF or VEGF response in the absence of Palomid 529, the results are presented.
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| Animal Protocol |
Mice: Palomid 529 (200 mg/kg/2d, i.p.) is pretreated for 1 week in 4- to 6-week-old female nude mice before 1×105 C6V10 rat glioma cells are injected subcutaneously. The course of treatment was continued while the tumors grew for 21 days. Nude mice receive s.c. injections of U87 cells (3×106/100 AL). Mice are treated with micronized Palomid 529 (P529) at doses of 50 mg and 25 mg/kg/2 d i.p., respectively, starting on day 3 following the injection of tumor cells. Control mice were those that weren't given any drugs. U87 tumors are given 24 days to grow. Tumor volumes are measured with a caliper and calculated as length×width×width×0.53 during drug therapy. After the animals have been put to sleep, the tumors are removed for immunohistologic and immunoblotting research.
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| References |
| Molecular Formula |
C24H22O6
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|---|---|
| Molecular Weight |
406.4279
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| Exact Mass |
406.14164
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| Elemental Analysis |
C, 70.92; H, 5.46; O, 23.62
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| CAS # |
914913-88-5
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| Related CAS # |
914913-88-5
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| Appearance |
white solid powder
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| SMILES |
CC(C1=CC2=C(C=C1)C3=CC(=C(C=C3OC2=O)OCC4=CC=C(C=C4)OC)OC)O
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| InChi Key |
YEAHTLOYHVWAKW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H22O6/c1-14(25)16-6-9-18-19-11-22(28-3)23(12-21(19)30-24(26)20(18)10-16)29-13-15-4-7-17(27-2)8-5-15/h4-12,14,25H,13H2,1-3H3
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| Chemical Name |
8-(1-hydroxyethyl)-2-methoxy-3-[(4-methoxyphenyl)methoxy]benzo[c]chromen-6-one
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| Synonyms |
SG 00529; -00529; SG00529; Palomid 529; Palomid-529; Palomid529; P529; P 529; P-529
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~81 mg/mL (~199.3 mM)
Water: <1 mg/mL Ethanol: <1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.15 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4604 mL | 12.3022 mL | 24.6045 mL | |
| 5 mM | 0.4921 mL | 2.4604 mL | 4.9209 mL | |
| 10 mM | 0.2460 mL | 1.2302 mL | 2.4604 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01033721 | Completed | Drug: Palomid 529 | Age-Related Macular Degeneration | Paloma Pharmaceuticals, Inc. | June 2010 | Phase 1 |
| NCT01271270 | Completed | Drug: Palomid 529 | Age-Related Macular Degeneration | National Eye Institute (NEI) | December 20, 2010 | Phase 1 |
P529 is a derivative of a nonsteroidal estrogen antagonist that maintains antiproliferative activity on endothelial cells while no longer inhibiting ER binding. Cancer Res. 2008 Nov 15;68(22):9551-7 |
P529 inhibition of retinal neovascularization. Cancer Res. 2008 Nov 15;68(22):9551-7 |
P529 inhibits glioma cell signaling, tumor growth, and tumor angiogenesis. Cancer Res. 2008 Nov 15;68(22):9551-7 |
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