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CUDC-305 is a novel synthetic HSP90 inhibitor with unique pharmacologic properties for cancer therapy.CUDC-305 shows high affinity for HSP90α/β (IC50, ～100 nmol/L) and HSP90 complex derived from cancer cells (IC50, 48.8 nmol/L). It displays potent antiproliferative activity against a broad range of cancer cell lines (mean IC50, 220 nmol/L). CUDC-305 exhibits high oral bioavailability (96.0%) and selective retention in tumor (half-life,20.4 hours) compared with normal tissues. Furthermore, CUDC-305 can cross bloodbrain barrier and reach therapeutic levels in brain tissue. CUDC-305 exhibits dosedependent antitumor activity in an s.c. xenograft model of U87MG glioblastoma and significantly prolongs animal survival in U87MG orthotopic model. CUDC-305 also displays potent antitumor activity in animal models of erlotinib-resistant non–small cell lung cancer and induces tumor regression in animal models of MDA-MB-468 breast cancer and MV4-11 acute myelogenous leukemia. Correlating with its efficacy in these various tumor models, CUDC-305 robustly inhibits multiple signaling pathways, including PI3K/AKT and RAF/MEK/ERK, and induces apoptosis. In combination studies, CUDC-305 enhances the antitumor activity of standard-of-care agents in breast and colorectal tumor models.
Patent: US20230218577A1 2023 Jul.
Use of heat shock protein inhibitors for the treatment of neurodevelopmental disorders
CUDC-305 purchased from AbMole
Patent. US2023218577A1 2023 Jul 13.
Patent. US2023218577A1
CUDC-305 purchased from AbMole
Sci Rep. 2017 Feb 8;7(1):201..
Proteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics
CUDC-305 purchased from AbMole
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Source | Scientific Reports (2017). Figure 1.CUDC305 (AbMole BioScience Houston, TX, USA) |
| Method | MTS based assay | |
| Cell Lines | 5637 bladder carcinoma cells | |
| Concentrations | 0, 0.01 nM, 0.1 nM, 1 nM, 10 nM, 100 nM, 1 μM, 10 μM, and 100 μM | |
| Incubation Time | 24, 48, or 72 h. | |
| Results | These results indicate that these HSP90 inhibitors potently inhibit cell proliferation and induce cell toxicity in bladder cancer 5637 cells. |
| Cell Experiment | |
|---|---|
| Cell lines | BT474, N87, H1975, H1993, Calu-6 and H460 cells line |
| Preparation method | Cell growth and viability assay. Human cancer cell lines were purchased from American Type Culture Collection and plated at 5,000 to 10,000 per well in 96-well plates with culture medium, as suggested by the provider. The cells were then incubated with compounds at various concentrations for 120 h. Growth inhibition was assessed by ATP content assay using the Perkin-Elmer ATPlite kit. Briefly, a 25-μL cell lysis solution was added to the 50-μL phenol red–free culture medium per well to lyse cells and stabilize ATP. Then 25-μL substrate solutions were added to the wells, and subsequently, luminescence was measured with a TopCount liquid scintillation analyzer (Perkin-Elmer). Values were expressed as a percentage relative to those obtained in untreated controls. IC50 values were calculated using PRISM software (GraphPad Software) with sigmoidal dose-response curve fitting. |
| Concentrations | 0~900nM |
| Incubation time | 120h |
| Animal Experiment | |
|---|---|
| Animal models | U87MG glioblastoma tumor models |
| Formulation | formulated in 30% Captisol |
| Dosages | single 160 mg/kg |
| Administration | oral gavage |
| Molecular Weight | 442.58 |
| Formula | C22H30N6O2S |
| CAS Number | 1061318-81-7 |
| Solubility (25°C) | DMSO 70 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related HSP Products |
|---|
| BIIB021
BIIB021 (CNF2024) is an orally available synthetic non-ansamycin Hsp90 inhibitor with ki value of 1.7nM. |
| Ganetespib
Ganetespib (STA-9090) is a potent synthetic small molecule inhibitor of Hsp90 with potential antineoplastic activity. |
| Luminespib (AUY922)
Luminespib (AUY922) is a small molecule Heat Shock Protein 90 (HSP90) inhibitor with IC50 values of 13 and 21 nM for HSP90α and HSP90β respectively. |
| NVP-HSP990
NVP-HSP990 is an orally bioavailable inhibitor of human heat-shock protein 90 (Hsp90) with IC50 values of 0.6, 0.8, and 8.5 nM for Hsp90α, Hsp90β, and Grp94, respectively. NVP-HSP990 has potential antineoplastic activity. |
| VER-82576
VER-82576 (NVP-BEP800) is a potent, orally available and selective inhibitor of Hsp90β with an IC50 of 58 nM. VER-82576 also slightly blocks Grp94 and Trap-1, with IC50s of 4.1 and 5.5 μM, respectively. |
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