Azeliragon

Azeliragon
Names
	IUPAC name 3-[4-[2-butyl-1-[4-(4-chlorophenoxy)phenyl]imidazol-4-yl]phenoxy]-N,N-diethylpropan-1-amine
Identifiers
CAS Number	603148-36-3;
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL3989929;
ChemSpider	9355214;
DrugBank	DB12689;
EC Number	814-441-9;
IUPHAR/BPS	8317;
KEGG	D11147;
PubChem CID	11180124;
UNII	LPU25F15UQ;
	InChI 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;
	SMILES CCCCC1=NC(=CN1C2=CC=C(C=C2)OC3=CC=C(C=C3)Cl)C4=CC=C(C=C4)OCCCN(CC)CC;
Properties
Chemical formula	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). Infobox references

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] 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[edit]

^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.

[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.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]