Azeliragon

Last updated
Azeliragon
Azeliragon.svg
Names
IUPAC name
3-[4-[2-butyl-1-[4-(4-chlorophenoxy)phenyl]imidazol-4-yl]phenoxy]-N,N-diethylpropan-1-amine
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
DrugBank
EC Number
  • 814-441-9
KEGG
PubChem CID
UNII
  • InChI=1S/C32H38ClN3O2/c1-4-7-9-32-34-31(25-10-16-28(17-11-25)37-23-8-22-35(5-2)6-3)24-36(32)27-14-20-30(21-15-27)38-29-18-12-26(33)13-19-29/h10-21,24H,4-9,22-23H2,1-3H3
    Key: KJNNWYBAOPXVJY-UHFFFAOYSA-N
  • CCCCC1=NC(=CN1C2=CC=C(C=C2)OC3=CC=C(C=C3)Cl)C4=CC=C(C=C4)OCCCN(CC)CC
Properties
C32H38ClN3O2
Molar mass 532.13 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Azeliragon (TTP488 or PF-04494700) is a small-molecule RAGE inhibitor. It is developed by vTv Therapeutics for various cancers, including triple-negative breast cancer [1] [2] and pancreatic cancer. [3]

The chemical reached Phase III trials in slowing cognitive deterioration in early stage Alzheimer's disease patients. [4] [5] [6] It was also tested in people with diabetic neuropathy [7] and animal models of graft-vs-host disease. [8]

References

  1. ↑ Magna, Melinda; Hwang, Gyong Ha; McIntosh, Alec; Drews-Elger, Katherine; Takabatake, Masaru; Ikeda, Adam; Mera, Barbara J.; Kwak, Taekyoung; Miller, Philip; Lippman, Marc E.; Hudson, Barry I. (13 July 2023). "RAGE inhibitor TTP488 (Azeliragon) suppresses metastasis in triple-negative breast cancer". npj Breast Cancer. 9 (1). 59. doi:10.1038/s41523-023-00564-9. ISSN   2374-4677. PMC   10344964 . PMID   37443146.
  2. ↑ Xie, Jizhao; Xu, Huanji; Wu, Xinduo; Xie, Yunfeng; Lu, Xiuhong; Wang, Lisheng (December 2021). "Design, synthesis and anti-TNBC activity of Azeliragon triazole analogues". Bioorganic & Medicinal Chemistry Letters. 54: 128444. doi:10.1016/j.bmcl.2021.128444. PMID   34763082. S2CID   243976660.
  3. ↑ Kong, Weikang; Zhu, Lingxia; Li, Tian; Chen, Jiao; Fan, Bo; Ji, Wenjing; Zhang, Chunli; Cai, Xueting; Hu, Chunping; Sun, Xiaoyan; Cao, Peng (June 2023). "Azeliragon inhibits PAK1 and enhances the therapeutic efficacy of AKT inhibitors in pancreatic cancer". European Journal of Pharmacology. 948: 175703. doi:10.1016/j.ejphar.2023.175703. PMID   37028543. S2CID   258019889.
  4. ↑ Burstein, A.H.; Sabbagh, M.; Andrews, R.; Valcarce, C.; Dunn, I.; Altstiel, L. (2018). "DEVELOPMENT OF AZELIRAGON, AN ORAL SMALL MOLECULE ANTAGONIST OF THE RECEPTOR FOR ADVANCED GLYCATION ENDPRODUCTS, FOR THE POTENTIAL SLOWING OF LOSS OF COGNITION IN MILD ALZHEIMER'S DISEASE". The Journal of Prevention of Alzheimer's Disease. 5 (2): 149–154. doi: 10.14283/jpad.2018.18 . PMID   29616709. S2CID   4592148.
  5. ↑ Yang, Lijuan; Liu, Yepei; Wang, Yuanyuan; Li, Junsheng; Liu, Na (2021). "Azeliragon ameliorates Alzheimer's disease via the Janus tyrosine kinase and signal transducer and activator of transcription signaling pathway". Clinics. 76: e2348. doi:10.6061/clinics/2021/e2348. PMC   7920406 . PMID   33681944.
  6. ↑ Burstein, Aaron H.; Dunn, Imogene; Gooch, Ann M.; Valcarce, Carmen (December 2020). "Effects of azeliragon on ADAS‐cog and CDR domains and individual items in patients with mild Alzheimer's disease and type 2 diabetes (T2D): Human/Human trials: Other". Alzheimer's & Dementia. 16 (S9). doi: 10.1002/alz.041198 . S2CID   227500289.
  7. ↑ Ma, Simeng; Nakamura, Yoki; Hisaoka-Nakashima, Kazue; Morioka, Norimitsu (February 2023). "Blockade of receptor for advanced glycation end-products with azeliragon ameliorates streptozotocin-induced diabetic neuropathy". Neurochemistry International. 163: 105470. doi:10.1016/j.neuint.2022.105470. PMID   36581174. S2CID   255113751.
  8. ↑ Joshi, Aditi A.; Wu, Ying; Deng, Songyan; Preston-Hurlburt, Paula; Forbes, Josephine M.; Herold, Kevan C. (December 2022). "RAGE antagonism with azeliragon improves xenograft rejection by T cells in humanized mice". Clinical Immunology. 245: 109165. doi:10.1016/j.clim.2022.109165. PMID   36257528. S2CID   252979084.
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