AFP-464 free base
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.
Price and Availability
AFP-464 free base, purity > 98%, is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.
Chemical Structure
Theoretical Analysis
MedKoo Cat#: 200123Name: AFP-464 free baseCAS#: 468719-52-0 (free base)Chemical Formula: C22H23F3N4O3Exact Mass: 448.1722Molecular Weight: 448.4462Elemental 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
Technical Data
Additional Information
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.
References
1. Kuffel MJ, Schroeder JC, Pobst LJ, et al.,Activation of the antitumor agent aminoflavone (NSC 686288) is mediatedby induction of tumor cell cytochrome P450 1A1/1A2. Mol Pharmacol2002:62:143-153.
2. Loaiza-Perez AI, Kenney S, Boswell J, et al., Sensitivity of renalcell carcinoma to aminoflavone: Role of CYP1A1. The Journal of Urology2004:171:1688-1697.
3. Loaiza-Perez AI, Kenney S, Boswell J, et al., Aryl hydrocarbonreceptor activation of an antitumor aminoflavone: Basis of selectivetoxicity for MCF-7 breast tumor cells. Mol Cancer Therapeutics2004:3(6):715-725.
4. Meng L, Kohlhagen G, Liao Z, et al., DNA-protein cross-links andreplication-dependent histone H2AX phosphorylation induced byaminoflavone (NSC 686288), a novel anticancer agent active against humanbreast cancer cells. Cancer Res 2005:65(12):5337-43.
5. Pobst LJ, Ames MM, et al., CYP1A1 activation of aminoflavone leads toDNA damage in human tumor cell lines. Cancer Chemother Pharmacol 2005.
