Radicicol 6-oxime
(Synonyms: KF25706)
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
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Size
Price
Stock
Quantity
Amount: USD 0.00
Please select quantity
or
or
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
- Protocols
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
Description
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[1].
IC50 & Target
[1]|
HSP90 5.5 nM (EC50) |
CDK4 |
Cellular Effect
|
Cell Line
|
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
Anti-cancerCell Cycle Regulation
Anti-cancer
Cell Cycle Regulation
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 (0.1-1 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].
Anti-cancer
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].
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.
Cell Proliferation Assay[1]
-
Cell Line:NRK, KNRK, 3Y1-B, SR-3Y1, SK-BR-3, MCF-7, DLD-1, HCT-116, A549, PC-3, DU145, A431
-
Concentration:Serial 3-fold dilutions
-
Incubation Time:72 h
-
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.
Western Blot Analysis[1]
-
Cell Line:K-ras-transformed rat NRK (KNRK5.2) cells
-
Concentration:0, 0.004, 0.01, 0.04, 0.12, 0.37, 1.1, 3.3, 10, 30 μM
-
Incubation Time:40 h
-
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.
Western Blot Analysis[1]
-
Cell Line:v-src-transformed rat 3Y1 (SR-3Y1) cells
-
Concentration:0, 0.004, 0.01, 0.04, 0.11, 0.33, 1 μM
-
Incubation Time:48 h
-
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.
Western Blot Analysis[1]
-
Cell Line:human breast carcinoma SK-BR-3 cells
-
Concentration:0, 0.004, 0.012, 0.037, 0.11, 0.33, 1 μM; 0.3 mM (kinetic analysis)
-
Incubation Time:Not explicitly stated (concentration-response); 2-40 h (kinetic analysis)
-
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
Anti-cancer
Radicicol 6-oxime (100 mg/kg; i.v.; twice daily; for 5 consecutive days) achieves a minimum T/C ratio of 0.058 in the MX-1 human breast cancer xenograft model, potently inhibits tumor growth in vivo, and depletes the Hsp90-associated signaling molecules Raf-1 and Cdk4[1].
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].
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.
-
Animal Model:BALB/c nu/nu nude mice (Nippon Clea Co.; n=5 per group)[1]
-
Dosage:100 mg/kg (twice daily); 100 mg/kg (once daily)
-
Administration:i.v.; twice daily (5 consecutive days); once daily (5 consecutive days)
-
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.
-
Animal Model:BALB/c nu/nu nude mice (Nippon Clea Co.; n=5 per group)[1]
-
Dosage:100 mg/kg
-
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.
-
Animal Model:BALB/c nu/nu nude mice (Nippon Clea Co.; n=5 per group)[1]
-
Dosage:100 mg/kg
-
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.
Related Protocols :
- Patient-Derived Xenograft (PDX)
- Patient-Derived Orthotopic Xenograft (PDOX)
- Splenic/Portal-Vein Liver Metastasis Xenograft
- Subcutaneous Cell-Line-Derived Xenograft
- Breast Cancer Modeling
- Orthotopic Cell-Line Xenograft
- Cell Viability Determination by MTT Colorimetric Assay
- Intraperitoneal/Peritoneal Dissemination Xenograft
Chemical Information
-
CAS No. 501124-40-9
-
Molecular Weight 379.79
-
Formula C18H18ClNO6
-
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
-
Synonyms
KF25706
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Molarity Calculator
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
=
×
×
Dilution Calculator
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Radicicol 6-oxime Related Classifications
HY-186321 Related Classifications
Powered by Bioz