WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 408039
Description: ADH-503 is a potent agonist of the integrin CD11b to mitigate myeloid cell immunosuppression. The partial activation of CD11b by ADH-503 leads to the repolarization of tumor-associated macrophages, reduction in the number of tumor-infiltrating immunosuppressive myeloid cells, and enhanced dendritic cell responses. These actions, in turn, improve antitumor T cell immunity and render checkpoint inhibitors effective in previously unresponsive PDAC models.
MedKoo Cat#: 408039
Chemical Formula: C28H32N2O4S2
Molecular Weight: 524.694
Elemental Analysis: C, 64.10; H, 6.15; N, 5.34; O, 12.20; S, 12.22
Synonym: ADH-503; ADH 503; ADH503;
IUPAC/Chemical Name: 2-hydroxy-N,N,N-trimethylethan-1-aminium (Z)-4-(5-((3-benzyl-4-methyl-2-thioxothiazolidin-5-ylidene)methyl)furan-2-yl)benzoate
InChi Key: HIJWAHUTJVGURK-GNWMQEPYSA-M
InChi Code: InChI=1S/C23H19NO3S2.C5H14NO/c1-15-21(29-23(28)24(15)14-16-5-3-2-4-6-16)13-19-11-12-20(27-19)17-7-9-18(10-8-17)22(25)26;1-6(2,3)4-5-7/h2-13,15H,14H2,1H3,(H,25,26);7H,4-5H2,1-3H3/q;+1/p-1/b21-13-;
SMILES Code: C(=O)([O-])C1C=CC(C2=CC=C(/C=C3\SC(=S)N(CC4=CC=CC=C4)C\3C)O2)=CC=1.[N+](CCO)(C)(C)C
Although checkpoint immunotherapies have revolutionized the treatment of cancer, not all tumor types have seen substantial benefit. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy in which very limited responses to immunotherapy have been observed. Extensive immunosuppressive myeloid cell infiltration in PDAC tissues has been postulated as a major mechanism of resistance to immunotherapy. Strategies concomitantly targeting monocyte or granulocyte trafficking or macrophage survival, in combination with checkpoint immunotherapies, have shown promise in preclinical studies, and these studies have transitioned into ongoing clinical trials for the treatment of pancreatic and other cancer types.
1. RZ Panni et al. Agonism of CD11b reprograms innate immunity to sensitize pancreatic cancer to immunotherapies. Sci Transl Med. 2019 Jul 3;11(499).
2. I Dickson. CD11b agonism overcomes PDAC immunotherapy resistance. Nat Rev Gastroenterol Hepatol. 2019 Sep;16(9):514.
3. D Maiguel et al. Small molecule-mediated activation of the integrin CD11b/CD18 reduces inflammatory disease. Sci Signal. 2011 Sep 6;4(189):ra57.