Radicicol 6-oxime
Radicicol 6-oxime (KF25706) is an Hsp90 inhibitor with an EC50 of 5.5 nM against human Hsp90. Radicicol 6-oxime binds to Hsp90 and disrupts its chaperone function, leading to destabilization and depletion of Hsp90-associated signaling molecules. Radicicol 6-oxime depletes Hsp90-associated signaling proteins such as Raf-1, v-src, p185erbB2, Cdk4, and mutant p53, thereby inhibiting K-ras and v-src signaling pathways. Radicicol 6-oxime exhibits antiproliferative activity against various tumor cells. Radicicol 6-oxime inhibits tumor growth in mouse tumor xenograft models. Radicicol 6-oxime can be used for research on breast cancer, colon cancer, and vulvar epidermoid carcinoma.
For research use only. We do not sell to patients.
- CAS No.: 501124-40-9
- Formula: C18H18ClNO6
- Molecular Weight:379.79
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
HSP90 5.5 nM (EC50) |
CDK4 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| NRK | IC50 |
80 nM
|
Antiproliferative activity against normal rat kidney epithelial NRK cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
Antiproliferative activity against normal rat kidney epithelial NRK cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
|
10383157 |
| SK-BR-3 | IC50 |
29 nM
|
Antiproliferative activity against human breast SK-BR-3 cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
Antiproliferative activity against human breast SK-BR-3 cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
|
10383157 |
| MCF7 | IC50 |
77 nM
|
Antiproliferative activity against human breast MCF-7 cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
Antiproliferative activity against human breast MCF-7 cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
|
10383157 |
| DLD-1 | IC50 |
40 nM
|
Antiproliferative activity against human colon DLD-1 cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
Antiproliferative activity against human colon DLD-1 cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
|
10383157 |
| HCT-116 | IC50 |
110 nM
|
Antiproliferative activity against human colon HCT-116 cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
Antiproliferative activity against human colon HCT-116 cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
|
10383157 |
| A549 | IC50 |
150 nM
|
Antiproliferative activity against human lung A549 cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
Antiproliferative activity against human lung A549 cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
|
10383157 |
| PC-3 | IC50 |
51 nM
|
Antiproliferative activity against human prostate PC-3 cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
Antiproliferative activity against human prostate PC-3 cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
|
10383157 |
| DU-145 | IC50 |
35 nM
|
Antiproliferative activity against human prostate DU145 cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
Antiproliferative activity against human prostate DU145 cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
|
10383157 |
| A-431 | IC50 |
210 nM
|
Antiproliferative activity against human vulva A431 cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
Antiproliferative activity against human vulva A431 cells assessed as reduction in cell viability incubated for 72 h by MTT assay.
|
10383157 |
In Vitro
Radicicol 6-oxime (Compound 5a) (serial 3-fold dilution; 72 h) potently inhibits the proliferation of multiple rat and human tumor cell lines in vitro, with IC50 values ranging from 26 nM (SR-3Y1) to 210 nM (A431)[1].
Radicicol 6-oxime (0.1-1 mM; 2-40 h) depletes multiple Hsp90-associated signaling proteins (p185erbB2, Raf-1, Cdk4, mutant p53) in SK-BR-3 cells in vitro in a concentration- and time-dependent manner, and protein depletion precedes the antiproliferative effect[1].
Radicicol 6-oxime (0-30 μM; 40 h) inhibits K-ras signaling in KNRK5.2 cells by depleting Raf-1 protein and reducing MAPK phosphorylation without altering K-ras or Erk2 levels[1].
Radicicol 6-oxime (0-1 μM; 48 h) inhibits v-src signaling in SR-3Y1 cells by depleting v-src protein and reducing total cellular tyrosine phosphorylation levels[1].
Radicicol 6-oxime (0.01-10 μM; 30 min) competes with Geldanamycin (HY-15230) for Hsp90 binding in vitro with an EC50 of 5.5 nM, which is consistent with its cellular antiproliferative potency[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:NRK, KNRK, 3Y1-B, SR-3Y1, SK-BR-3, MCF-7, DLD-1, HCT-116, A549, PC-3, DU145, A431
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Concentration:Serial 3-fold dilutions
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Incubation Time:72 h
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Result:Exhibited potent antiproliferative activity across all tested cell lines, with IC50 values in the nanomolar range.
Showed IC50 value of 80 nM in NRK cells.
Showed IC50 value of 39 nM in KNRK cells.
Showed IC50 value of 90 nM in 3Y1-B cells.
Showed IC50 value of 26 nM in SR-3Y1 cells.
Showed IC50 value of 29 nM in SK-BR-3 cells.
Showed IC50 value of 77 nM in MCF-7 cells.
Showed IC50 value of 40 nM in DLD-1 cells.
Showed IC50 value of 110 nM in HCT-116 cells.
Showed IC50 value of 150 nM in A549 cells.
Showed IC50 value of 51 nM in PC-3 cells.
Showed IC50 value of 35 nM in DU145 cells.
Showed IC50 value of 210 nM in A431 cells.
Was slightly more potent than radicicol against these human tumor cell lines on average.
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Cell Line:K-ras-transformed rat NRK (KNRK5.2) cells
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Concentration:0, 0.004, 0.01, 0.04, 0.12, 0.37, 1.1, 3.3, 10, 30 μM
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Incubation Time:40 h
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Result:Depleted Raf-1 protein in a concentration-dependent manner.
Inhibited K-ras-induced phosphorylation of MAPK.
Showed little to no effect on Erk2 and K-ras protein expression levels.
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Cell Line:v-src-transformed rat 3Y1 (SR-3Y1) cells
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Concentration:0, 0.004, 0.01, 0.04, 0.11, 0.33, 1 μM
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Incubation Time:48 h
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Result:Decreased the level of total tyrosine phosphorylation of cellular proteins in a concentration-dependent manner.
Depleted v-src protein from the cells.
Did not change Erk2 protein levels.
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Cell Line:human breast carcinoma SK-BR-3 cells
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Concentration:0, 0.004, 0.012, 0.037, 0.11, 0.33, 1 μM; 0.3 mM (kinetic analysis)
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Incubation Time:Not explicitly stated (concentration-response); 2-40 h (kinetic analysis)
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Result:Completely depleted p185erbB2 protein at 0.1 mM.
Depleted p185erbB2 in a concentration-dependent manner.
Depleted Raf-1, Cdk4, and mutant p53 proteins.
Did not change Erk2 protein levels even at 1 mM.
Depleted p185erbB2 protein to basal levels by 16 h at 0.3 mM.
Depleted Raf-1 and Cdk4 within 24 h at 0.3 mM.
Induced cell growth inhibition with IC50 < 100 μM after 8 h of treatment.
In Vivo
Radicicol 6-oxime (100 mg/kg; i.v.; twice daily; for 5 consecutive days) achieves a minimum T/C ratio of 0.33 in the MCF-7 human breast cancer xenograft model, exerting significant antitumor activity[1].
Radicicol 6-oxime (100 mg/kg; i.v.; twice daily; for 5 days) exhibits moderate antitumor activity with a minimum T/C ratio of 0.57 in the DLD-1 human colon cancer xenograft model[1].
Radicicol 6-oxime (100 mg/kg; i.v.; twice daily; for 5 consecutive days) achieves a minimum T/C ratio of 0.54 in the A431 human epidermoid carcinoma xenograft model, exerting moderate antitumor activity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nu/nu nude mice (Nippon Clea Co.; n=5 per group)[1]
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Dosage:100 mg/kg (twice daily); 100 mg/kg (once daily)
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Administration:i.v.; twice daily (5 consecutive days); once daily (5 consecutive days)
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Result:Achieved a minimum T/C ratio of 0.058 against MX-1 xenografts at 100 mg/kg twice daily for 5 days.
Achieved a minimum T/C ratio of 0.49 against MX-1 xenografts at 100 mg/kg once daily for 5 days.
Markedly decreased Raf-1 and Cdk4 protein levels in MX-1 tumor specimens collected on day 5.
Slightly declined Erk2 protein levels in MX-1 tumor specimens collected on day 5.\nAchieved a minimum T/C ratio of 0.33 against MCF-7 xenografts at 100 mg/kg twice daily for 5 days.
Achieved a minimum T/C ratio of 0.78 against MCF-7 xenografts at 100 mg/kg once daily for 5 days.
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Animal Model:BALB/c nu/nu nude mice (Nippon Clea Co.; n=5 per group)[1]
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Dosage:100 mg/kg
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Administration:i.v.; twice daily; 5 consecutive days
-
Result:Achieved a minimum T/C ratio of 0.57 against DLD-1 xenografts at 100 mg/kg twice daily for 5 days.
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Animal Model:BALB/c nu/nu nude mice (Nippon Clea Co.; n=5 per group)[1]
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Dosage:100 mg/kg
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Administration:i.v.; twice daily; 5 consecutive days
-
Result:Achieved a minimum T/C ratio of 0.54 against A431 xenografts at 100 mg/kg twice daily for 5 days.
Chemical Information
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CAS No. 501124-40-9
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Molecular Weight 379.79
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Formula C18H18ClNO6
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SMILES
OC1=CC(O)=C(Cl)C2=C1C(O[C@H](C)C[C@](O3)([H])[C@@]3([H])/C=C/C=C\C(C2)=N/O)=O
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Synonyms
KF25706
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Patient-Derived Xenograft (PDX)
Patient-derived xenograft (PDX) models are generated by engrafting primary human tumor tissue directly into immunodeficient mice, allowing in vivo propagation of patient tumor biology without initial in vitro adaptation. These models are used to preserve key histopathological and molecular characteristics of the original tumor and enable assessment of tumor growth dynamics and therapeutic response in a living organism. The biological readout is tumor engraftment and subsequent growth in the murine host, which reflects the ability of human tumor cells to survive, vascularize, and expand in an immunocompromised microenvironment.
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Patient-Derived Orthotopic Xenograft (PDOX)
Patient-derived orthotopic xenograft (PDOX) modeling implants fresh patient tumor tissue or patient-derived tumor cells into the anatomically corresponding organ or tissue site of immunodeficient mice, usually by surgical orthotopic implantation, to preserve patient tumor histology, local microenvironmental context, invasion, metastatic behavior, and treatment-response features better than subcutaneous implantation. PDOX readouts include tumor engraftment, orthotopic tumor growth, local invasion, metastasis, recurrence after resection, histologic similarity to the donor tumor, biomarker retention, molecular concordance, survival, and response or resistance to therapy. PDOX models are used for preclinical drug testing and individualized therapy evaluation, but engraftment success varies by tumor type and specimen quality.
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Splenic/Portal-Vein Liver Metastasis Xenograft
Splenic and portal-vein liver metastasis xenograft models deliver tumor cells into the portal circulation so that cells reach the liver first and form hepatic metastatic lesions; splenic injection uses the spleen as an access route to the portal system, while direct portal-vein injection introduces cells into the portal vein without requiring splenectomy. The assay detects liver colonization, intrahepatic tumor growth, tumor distribution, treatment response, survival, and liver-metastasis microenvironment changes; readouts include bioluminescence or fluorescence imaging, gross liver nodule counts, liver weight or tumor burden, histology, and survival.
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Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
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Orthotopic Cell-Line Xenograft
Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
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Intraperitoneal/Peritoneal Dissemination Xenograft
Intraperitoneal (IP) or peritoneal dissemination xenograft models are based on the introduction of human cancer cells into the peritoneal cavity of immunodeficient mice, where they attach to peritoneal surfaces, form multicellular aggregates or spheroids, and progressively generate disseminated tumor nodules that mimic advanced peritoneal metastatic disease. These models are widely used to study ovarian cancer progression, tumor-microenvironment interactions, and intraperitoneal therapeutic responses, often incorporating bioluminescence or fluorescence imaging to longitudinally monitor tumor burden in vivo. The biological principle relies on the capacity of tumor cells such as SKOV3 or related ovarian carcinoma lines to survive in suspension, aggregate within ascites-like fluid, adhere to mesothelial surfaces, and invade peritoneal organs, thereby recapitulating human peritoneal carcinomatosis patterns observed in advanced disease.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)