AFP-464 mesylate
AFP-464 is a synthetic lysyl prodrug of the amino-substituted flavone derivate aminoflavone with antiproliferative and antineoplastic activities. AFP464 is rapidly converted to aminoflavone in plasma. Aminoflavone activates the aryl hydrocarbon receptor (AhR) signaling pathway leading to an increase in cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1A2 (CYP1A2) expression and, to a lesser extent, an increase in cytochrome P450 1B1 (CYP1B1) expression. Subsequently, aminoflavone is metabolized to toxic metabolites by the cytochromome P450 enzymes that it induces; these toxic metabolites covalently bind to DNA, resulting in the phosphorylation of p53, the induction of the p53 downstream target p21Waf1/Cip1, and apoptosis.
1. Kuffel MJ, Schroeder JC, Pobst LJ, et al., Activation of the antitumor agent aminoflavone (NSC 686288) is mediated by induction of tumor cell cytochrome P450 1A1/1A2. Mol Pharmacol 2002:62:143-153.
2. Loaiza-Perez AI, Kenney S, Boswell J, et al., Sensitivity of renal cell carcinoma to aminoflavone: Role of CYP1A1. The Journal of Urology 2004:171:1688-1697.
3. Loaiza-Perez AI, Kenney S, Boswell J, et al., Aryl hydrocarbon receptor activation of an antitumor aminoflavone: Basis of selective toxicity for MCF-7 breast tumor cells. Mol Cancer Therapeutics 2004:3(6):715-725.
4. Meng L, Kohlhagen G, Liao Z, et al., DNA-protein cross-links and replication-dependent histone H2AX phosphorylation induced by aminoflavone (NSC 686288), a novel anticancer agent active against human breast cancer cells. Cancer Res 2005:65(12):5337-43.
5. Pobst LJ, Ames MM, et al., CYP1A1 activation of aminoflavone leads to DNA damage in human tumor cell lines. Cancer Chemother Pharmacol 2005.
2. Loaiza-Perez AI, Kenney S, Boswell J, et al., Sensitivity of renal cell carcinoma to aminoflavone: Role of CYP1A1. The Journal of Urology 2004:171:1688-1697.
3. Loaiza-Perez AI, Kenney S, Boswell J, et al., Aryl hydrocarbon receptor activation of an antitumor aminoflavone: Basis of selective toxicity for MCF-7 breast tumor cells. Mol Cancer Therapeutics 2004:3(6):715-725.
4. Meng L, Kohlhagen G, Liao Z, et al., DNA-protein cross-links and replication-dependent histone H2AX phosphorylation induced by aminoflavone (NSC 686288), a novel anticancer agent active against human breast cancer cells. Cancer Res 2005:65(12):5337-43.
5. Pobst LJ, Ames MM, et al., CYP1A1 activation of aminoflavone leads to DNA damage in human tumor cell lines. Cancer Chemother Pharmacol 2005.
| Chemical | |
|---|---|
| CAS Num | 468719-52-0 |
| Chemical Formula | C23H27F3N4O6S |
| Molecular Weight | 544.5462 |
| IUPAC Chemical Name | (2S)-2,6-diamino-N-[4-(5-amino-6,8-difluoro-7-methyl-4-oxochromen-2-yl)-2-fluorophenyl]hexanamide, methanesulfonic acid |
| Elemental Analysis | C, 50.73; H, 5.00; F, 10.47; N, 10.29; O, 17.63; S, 5.89 |
| Synonym | AFP464; AFP 464; AFP-464; AFP-464 mesylate |
| Solubility | Soluble in DMSO, not in water |
| SMILES Code | O=C(NC1=CC=C(C2=CC(C3=C(O2)C(F)=C(C)C(F)=C3N)=O)C=C1F)[C@@H](N)CCCCN.CS(=O)(O)=O |
| Biological | |
| Targets and Effects | aryl hydrocarbon receptor (AhR) |
| Pathways | Apoptosis |
| Physical | |
| Appearance | Solid powder |
| Purity | >98% (or refer to the Certificate of Analysis) |
| Shipping Condition | Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs. |
| Storage Condition | Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years). |
| Shelf Life | >5 years if stored properly |
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