Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C22H23F3N4O3.2CH4O3S |
Molecular Weight | 640.65 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CS(O)(=O)=O.CS(O)(=O)=O.CC1=C(F)C(N)=C2C(=O)C=C(OC2=C1F)C3=CC=C(NC(=O)[C@@H](N)CCCCN)C(F)=C3
InChI
InChIKey=FDQJDUBLCBZBCQ-GXKRWWSZSA-N
InChI=1S/C22H23F3N4O3.2CH4O3S/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;2*1-5(2,3)4/h5-6,8-9,13H,2-4,7,26-28H2,1H3,(H,29,31);2*1H3,(H,2,3,4)/t13-;;/m0../s1
Kirax Corporation (formerly Tigris Pharmaceuticals) was developing AFP-464, a lysyl prodrug of aminoflavone for the treatment of solid tumours. AFP-464 is an antitumor agent which was in phase II clinical trials, acts against estrogen-positive breast cancer (ER+). AFP-464, has a unique mechanism of action by activating aryl hydrocarbon receptor (AhR) signaling pathway. Preclinical studies into AFP-464's mechanism of action have shown that AFP-464 is converted to metabolites, which bind covalently to DNA, resulting in p53 activation and apoptosis. AFP-464 has shown a unique pattern of growth inhibitory activity in the NCI's 60 tumor cell line screen, with breast, ovarian, lung and renal tumor cell lines exhibiting particular sensitivity to the compound. In vivo anti-tumor activity of AFP-464 has been demonstrated in several xenograft studies in mice bearing renal and breast cancer. Preclinical studies have shown that tumors (breast, ovarian, pancreatic and renal) with AhR localized in the cytoplasm are very sensitive to AFP-464 while those with AhR localized in the nucleus are more resistant. AFP-464 was being studied by Tigris Pharmaceuticals in a randomized Phase 2 clinical trial with ER-positive breast cancer patients. However, AFP-464 development was discontinued.
Originator
Approval Year
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01233947
Breast neoplasm: 74 mg/m2 AFP-464 administered as a 3 hour IV infusion on Days 1 and 8 of a 21-day cycle.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28471540
The incubation of TK-10, SN12C and Caki-1 cells with 1 uM AFP-464 for 5 days induced
a significant decrease in cell viability (compared to control viability, considered to be
100%: TK-10, 21.22±10.9%; SN12C, 50.91±4.9%; Caki-1, 87.24±9.1% cells).
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C2163
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C48370
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100000174975
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PARENT (SALT/SOLVATE)
SUBSTANCE RECORD