CAS 65646-68-6|Fenretinide
Introduction：Basic information about CAS 65646-68-6|Fenretinide, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | Fenretinide | ||
|---|---|---|---|
| CAS Number | 65646-68-6 | Molecular Weight | 391.546 |
| Density | 1.1±0.1 g/cm3 | Boiling Point | 597.6±42.0 °C at 760 mmHg |
| Molecular Formula | C26H33NO2 | Melting Point | 162-163°C |
| MSDS | ChineseUSA | Flash Point | 315.2±27.9 °C |
| Symbol | GHS07, GHS08 | Signal Word | Danger |
Names
| Name | 4-hydroxyphenyl retinamide |
|---|---|
| Synonym | More Synonyms |
Fenretinide BiologicalActivity
| Description | Fenretinide is a synthetic retinoid deriverative, binding to the retinoic acid receptors (RAR) at concentrations necessary to induce cell death. |
|---|---|
| Related Catalog | Signaling Pathways >>Autophagy >>AutophagySignaling Pathways >>Metabolic Enzyme/Protease >>RAR/RXRResearch Areas >>Cancer |
| In Vitro | Fenretinide exerts not just acute but also long term antitumor activity in selected T-ALL cell lines. Fenretinide inhibits DES activity in CCRF-CEM leukemia cells in a dose and time dependent manner, leading to a concomitant increase of the endogenous cellular dhCer content. Fenretinide (3 μM)-induced dhCer accumulation in both CCRF-CEM and Jurkat cells[1]. Ceramide inhibition with fenretinide protects insulin signaling. Fenretinide prevents lipid-induced reductions in insulin-stimulated glucose uptake[2]. Fenretinide inhibits OVCAR-5 cell proliferation and viability at concentrations higher than 1 microM, with 70-90% growth inhibition at 10 microM. Fenretinide (1 microM) significantly inhibits OVCAR-5 invasion after 3 days preincubation. Endothelial cells treated with 1 microM 4-HPR fails to form tubes, but forms small cellular aggregates[4]. |
| In Vivo | Fenretinide (10 mg/kg, i.p.) selectively inhibits ceramide accumulation HFD-fed male C57Bl/6 mice. Fenretinide treatment improves glucose tolerance and insulin sensitivity as determined by both glucose and insulin tolerance tests[2]. Addition of 25 mg/kg ketoconazole to Fenretinide in NOD/SCID mice increased 4-HPR plasma levels[3]. |
| Cell Assay | Standard XTT assay is used to determine cell viability. For fenretinide-only treatments, cells are plated in 96-well plates at 750,000 cells/mL and 100 μL/well. After 4 h, treatments are added on 50 μL/well obtaining a final density of 500,000 cells/mL and final volume of 150 μL/well. Four replicates are used per experimental condition. XTT reagent mixture is added 4 h before the end of selected treatment period and absorbance at 490 nm is determined per each well. A slightly modified protocol is used for analysis of the effect of myriocin (final concentration of 100 nM) or antioxidant on Fenretinide treatment. Briefly, cells are seeded on 60 mm culture dishes and myriocin or antioxidants added after 4 h. Fenretinide treatment is added 2 h later and cells are plated in quadruplicates in 96 well plates (150 μL/well). |
| Animal Admin | Male mice (C57Bl6) are fed a standard chow or a high-fat diet (HFD) from 5 to 17 weeks, at which point half of the HFD-fed mice begin receiving fenretinide in drinking water for 4 weeks. Fenretinide is dissolved in 100% ethanol and diluted in water to 10 μg/mL. Control treatment water receives an equal amount of ethanol (0.5%). FEN water is prepared in low-light conditions and administered in light-protective bottles. Water is replaced every 1-2 days, and no precipitation of FEN is noted at any time. Animal weights are recorded at the beginning and end of the treatment period. Following a 4-week FEN treatment, mice undergo intraperitoneal glucose and insulin tolerance tests. For both tests, mice are fasted for 6 h andreceive an injection of either glucose (1 g/kg of body weight) or insulin (0.75 units/kg of body weight). Blood glucose is determined at the times indicated by the Bayer Contour® glucose meter, and insulin is measured with the rat/mouse insulin ELISA kit. The insulin resistance index is assessed by using fasting blood glucose and insulin levels to compute the homeostatic model assessment of insulin resistance (HOMA-IR), where a higher number represents greater insulin resistance. |
| References | [1]. Apraiz, Aintzane., et al. Dihydroceramide accumulation and reactive oxygen species are distinct and nonessential events in 4-HPR-mediated leukemia cell death. Biochemistry and Cell Biology (2012), 90(2), 209-223. [2]. Bikman, Benjamin T., et al. Fenretinide Prevents Lipid-induced Insulin Resistance by Blocking Ceramide Biosynthesis. Journal of Biological Chemistry (2012), 287(21), 17426-17437. [3]. Cooper JP, et al. Fenretinide metabolism in humans and mice: utilizing pharmacological modulation of its metabolic pathway to increase systemic exposure. Br J Pharmacol. 2011 Jul;163(6):1263-75. [4]. Golubkov V, et al. Action of fenretinide (4-HPR) on ovarian cancer and endothelial cells. Anticancer Res. 2005 Jan-Feb;25(1A):249-53. |
Chemical & Physical Properties
| Density | 1.1±0.1 g/cm3 |
|---|---|
| Boiling Point | 597.6±42.0 °C at 760 mmHg |
| Melting Point | 162-163°C |
| Molecular Formula | C26H33NO2 |
| Molecular Weight | 391.546 |
| Flash Point | 315.2±27.9 °C |
| Exact Mass | 391.251129 |
| PSA | 49.33000 |
| LogP | 7.41 |
| Vapour Pressure | 0.0±1.8 mmHg at 25°C |
| Index of Refraction | 1.607 |
| InChIKey | AKJHMTWEGVYYSE-FXILSDISSA-N |
| SMILES | CC(C=CC1=C(C)CCCC1(C)C)=CC=CC(C)=CC(=O)Nc1ccc(O)cc1 |
| Storage condition | −20°C |
| Stability | Light Sensitive - Protect from Light Exposure |
Toxicological Information
CHEMICAL IDENTIFICATION |
ACUTE TOXICITY DATA - TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Human - man
- DOSE/DURATION :
- 180 mg/kg/18D-I
- TOXIC EFFECTS :
- Sense Organs and Special Senses (Eye) - retinal changes (pigmentary depositions, retinitis, other)
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Human - woman
- DOSE/DURATION :
- 210 mg/kg/2W-I
- TOXIC EFFECTS :
- Sense Organs and Special Senses (Eye) - retinal changes (pigmentary depositions, retinitis, other)
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 8388 mg/kg/21D-I
- TOXIC EFFECTS :
- Blood - changes in other cell count (unspecified)
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Intraperitoneal
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 2138 mg/kg/21D-I
- TOXIC EFFECTS :
- Blood - pigmented or nucleated red blood cells Blood - changes in erythrocyte (RBC) count Blood - changes in leukocyte (WBC) count
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 600 mg/kg
- SEX/DURATION :
- female 10-11 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 400 mg/kg
- SEX/DURATION :
- female 11 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Specific Developmental Abnormalities - musculoskeletal system
MUTATION DATA - TYPE OF TEST :
- Morphological transformation
- TEST SYSTEM :
- Rodent - mouse Mammary gland
- DOSE/DURATION :
- 10 umol/L
- REFERENCE :
- NUCADQ Nutrition and Cancer. (Franklin Institute Press, POB 2266, Phildelphia, PA 19103) V.1- 1978- Volume(issue)/page/year: 7,105,1985
- TYPE OF TEST :
- Morphological transformation
- TEST SYSTEM :
- Rodent - mouse Mammary gland
- DOSE/DURATION :
- 10 umol/L
- REFERENCE :
- NUCADQ Nutrition and Cancer. (Franklin Institute Press, POB 2266, Phildelphia, PA 19103) V.1- 1978- Volume(issue)/page/year: 7,105,1985
Safety Information
| Symbol | GHS07, GHS08 |
|---|---|
| Signal Word | Danger |
| Hazard Statements | H302 + H312 + H332-H315-H319-H335-H360 |
| Precautionary Statements | P201-P261-P280-P305 + P351 + P338-P308 + P313 |
| Personal Protective Equipment | Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges |
| Hazard Codes | T: Toxic; |
| Risk Phrases | R60;R61;R20/21/22;R36/37/38 |
| Safety Phrases | S53-S26-S36/37/39-S45 |
| RIDADR | NONH for all modes of transport |
| WGK Germany | 3 |
| RTECS | VH6420000 |
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| Enhanced killing of SCC17B human head and neck squamous cell carcinoma cells after photodynamic therapy plus fenretinide via the de novo sphingolipid biosynthesis pathway and apoptosis. Int. J. Oncol. 46(5) , 2003-10, (2015) Because photodynamic therapy (PDT) alone is not always effective as an anticancer treatment, PDT is combined with other anticancer agents for improved efficacy. The clinically-relevant fenretinide [N-... | |
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Synonyms
| 4-Hydroxyphenyl retinamide |
| Fenretinide |
| 4-HPR |
| 15-[(4-Hydroxyphenyl)amino]retinal |
| fenretinida |
| Retinal, 15-[(4-hydroxyphenyl)amino]- |
| fenretinidum |
| MFCD00792674 |
