WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200123
CAS#: 468719-52-0 (free base)
Description: 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.
MedKoo Cat#: 200123
Name: AFP-464 free base
CAS#: 468719-52-0 (free base)
Chemical Formula: C22H23F3N4O3
Exact Mass: 448.1722
Molecular Weight: 448.4462
Elemental Analysis: C, 58.92; H, 5.17; F, 12.71; N, 12.49; O, 10.70
Related CAS #: 468719-52-0 (free base) 1350966-83-4 (mesylate 1:1) 468719-53-1 (mesylate 1:3) 1523457-12-6 (HBr 1:1) 468719-51-9 (HBr 1:3)
Synonym: AFP464; AFP 464; AFP-464; AFP-464 mesylate
IUPAC/Chemical Name: (2S)-2,6-diamino-N-[4-(5-amino-6,8-difluoro-7-methyl-4-oxochromen-2-yl)-2-fluorophenyl]hexanamide
InChi Key: WHWJKUICJXPKFQ-ZDUSSCGKSA-N
InChi Code: InChI=1S/C22H23F3N4O3/c1-10-18(24)20(28)17-15(30)9-16(32-21(17)19(10)25)11-5-6-14(12(23)8-11)29-22(31)13(27)4-2-3-7-26/h5-6,8-9,13H,2-4,7,26-28H2,1H3,(H,29,31)/t13-/m0/s1
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
According to http://www.tigrispharma.com/afp464.html, AFP-464, a lysyl pro-drug of aminoflavone (AF), is synthesized to improve the aqueous solubility of the parent compound AF. AFP-464 undergoes rapid conversion to AF in plasma by nonspecific plasma esterases. AF is an investigational anticancer agent with a unique pattern of growth inhibitory activity in the NCI 60 tumor cell line screen (COMPARE analysis; http://www.dtp.nci.nih.gov), suggesting a novel mechanism of action. Human tumor cell lines that exhibited particular sensitivity to AF included those of breast and renal origin. In vivo antitumor activity of AF was demonstrated in several xenograft studies in mice bearing A-498, CaKi-1 renal and MCF-7 breast cancer. Previous studies with human breast and renal cancer cell lines showed that AF induced CYP1A1/1A2 and CYP1B1 protein expression and was converted to metabolites that were covalently bound to DNA. This resulted in phosphorylation of p53 with induction of the p53 downstream target p21Waf1/Cip1 and apotosis.
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.