U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of AFP-464

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

HIDE SMILES / InChI

Molecular Formula CH4O3S
Molecular Weight 96.106
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C22H23F3N4O3
Molecular Weight 448.4382
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

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.

Approval Year

PubMed

PubMed

TitleDatePubMed
In Vitro Antitumor Effects of AHR Ligands Aminoflavone (AFP 464) and Benzothiazole (5F 203) in Human Renal Carcinoma Cells.
2017 Dec
The Immune System As a New Possible Cell Target for AFP 464 in a Spontaneous Mammary Cancer Mouse Model.
2017 Sep

Sample Use Guides

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
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).
Substance Class Chemical
Created
by admin
on Sat Dec 16 07:33:12 GMT 2023
Edited
by admin
on Sat Dec 16 07:33:12 GMT 2023
Record UNII
73JNH95XPX
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AFP-464
Common Name English
AFP464
Code English
AFP 464 [WHO-DD]
Common Name English
HEXANAMIDE, 2,6-DIAMINO-N-(4-(5-AMINO-6,8-DIFLUORO-7-METHYL-4-OXO-4H-1-BENZOPYRAN-2-YL)-2-FLUOROPHENYL)-, (2S)-, METHANESULFONATE (1:2)
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C2163
Created by admin on Sat Dec 16 07:33:12 GMT 2023 , Edited by admin on Sat Dec 16 07:33:12 GMT 2023
Code System Code Type Description
PUBCHEM
21144069
Created by admin on Sat Dec 16 07:33:12 GMT 2023 , Edited by admin on Sat Dec 16 07:33:12 GMT 2023
PRIMARY
CAS
468719-53-1
Created by admin on Sat Dec 16 07:33:12 GMT 2023 , Edited by admin on Sat Dec 16 07:33:12 GMT 2023
PRIMARY
FDA UNII
73JNH95XPX
Created by admin on Sat Dec 16 07:33:12 GMT 2023 , Edited by admin on Sat Dec 16 07:33:12 GMT 2023
PRIMARY
NCI_THESAURUS
C48370
Created by admin on Sat Dec 16 07:33:12 GMT 2023 , Edited by admin on Sat Dec 16 07:33:12 GMT 2023
PRIMARY
SMS_ID
100000174975
Created by admin on Sat Dec 16 07:33:12 GMT 2023 , Edited by admin on Sat Dec 16 07:33:12 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE