CD437 is a retinoic acid receptor (RAR)γ-selective agonist, γ-selective retinoid; potent inducer of apoptosis. It displays RARγ-dependent and -independent effects on differentiation and apoptosis. CD437 reduces the numbers of H460, SK-MES-1, A549, and H292 cells with 50% inhibitory values of approximately 0.5, 0.4, 3, and 0.85 μM, respectively. Treatment for 72 h with CD437 causes a strong dose-dependent growth inhibition in all melanoma cell lines. At a concentration of 5 μM CD437, only about 5 to 25% of the cells remain viable after 3 d. The concentrations of CD437 required for 50% growth inhibition (IC50) range from 10 μM for MeWo to 0.1 μM for SK-Mel-23 showing the highest sensitivity.
In vivo, tumors in CD437-treated mice stop growing, an effect that becomes already statistically significant (P<0.01) at day 13, 3 d after first administration of CD437, and is maintained for more than 3 wk after discontinuation of treatment. Further histologic analysis demonstrates marked c-fos mRNA levels at the tumor-stroma edge in CD437-treated tumors.
|Animal models||Male Swiss-nu/nu mice weighing 20 to 25 g|
|Dosages||10 mg/kg/body weight and 30 mg/kg/body weight|
|Administration||injected intratumorally or fed|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO: 100 mg/mL (Need ultrasonic and warming)|
Molecular determinants of AHPN (CD437)-induced growth arrest and apoptosis in human lung cancer cell lines.
Li Y, et al. Mol Cell Biol. 1998 Aug;18(8):4719-31. PMID: 9671482.
Treatment of melanoma cells with the synthetic retinoid CD437 induces apoptosis via activation of AP-1 in vitro, and causes growth inhibition in xenografts in vivo.
Schadendorf D, et al. J Cell Biol. 1996 Dec;135(6 Pt 2):1889-98. PMID: 8991099.
|Related RAR/RXR Products|
HX 531 is a potent antagonist of retinoid X receptors (IC50 = 18 nM).
MM11253 (SR11253) is a high-affinity RARγ-selective retinoid acid (RA) receptor antagonist (IC50 = 44 nM against ATRA for binding RARγ; IC50 =1 μM in case of RARα, RARβ, RXRα).
Bexarotene is a retinoid specifically selective for retinoid X receptors, used as an oral antineoplastic agent in the treatment of cutaneous T-cell lymphoma.
Tazarotene, a new member of the acetylenic class of RARβ/γ selective retinoids which is approved to treat a variety of skin diseases, exhibits an anti-proliferative effect in human basal cell carcinoma (BCC) by triggering caspase-dependent apoptosis.
Fenretinide (4-HPR) is a synthetic retinoid deriverative. Fenretinide is shown to exhibit binding to the retinoic acid receptors (RAR) at concentrations necessary to induce cell death.
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