MC-Val-Cit-PAB-Amide-TLR7 agonist 4 (example 15) is a conjugate that acts as an immune agonist targeting both HER2-TLR7 and HER2-TLR8 pathways [1].

Talabostat (PT100, Val-boroPro) is a potent, nonselective and orally available dipeptidyl peptidase IV (DPP-IV) inhibitor with a Ki of 0.18 nM. Talabostat is a nonselective DPP-IV inhibitor, inhibiting DPP8/9, FAP, DPP2 and some other DASH family enzymes essentially as potently as it inhibits DPP-IV[1]. Talabostat stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis. The inhibition of two serine proteases, DPP8 and DPP9, activates the proprotein form of caspase-1 independent of the inflammasome adaptor ASC[2]. Talabostat competitively inhibits the dipeptidyl peptidase (DPP) activity of FAP and CD26/DPP-IV, and there is a high-affinity interaction with the catalytic site due to the formation of a complex between Ser630/624 and the boron of talabostat[3]. Talabostat can stimulate immune responses against tumors involving both the innate and adaptive branches of the immune system. In WEHI 164 fibrosarcoma and EL4 and A20/2J lymphoma models, PT-100 causes regression and rejection of tumors. The antitumor effect appears to involve tumor-specific CTL and protective immunological memory. Talabostat treatment of WEHI 164-inoculated mice increases mRNA expression of cytokines and chemokines known to promote T-cell priming and chemoattraction of T cells and innate effector cells[3]. Talabostat treated mice show significant less fibrosis and FAP expression is reduced. Upon PT100 treatment, significant differences in the MMP-12, MIP-1α, and MCP-3 mRNA expression levels in the lungs are also observed. Treatment with PT100 in this murine model of pulmonary fibrosis has an anti-fibro-proliferative effect and increases macrophage activation[4]. [1]. Connolly BA, et al. Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potencyand in vivo efficacy and safety. J Med Chem. 2008 Oct 9;51(19):6005-13. [2]. Okondo MC, et al. DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat Chem Biol. 2017 Jan;13(1):46-53. [3]. Adams S, et al. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004 Aug 1;64(15):5471-80. [4]. Egger C, et al. Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis. Eur J Pharmacol. 2017 Aug 15;809:64-72.

Adrenocorticotropic Hormone (ACTH) (4-10) is an agonist of potent melanocortin(MC4R) receptor .

(p-Iodo-Phe7)-ACTH (4-10), a derivative of adrenocorticotrophic hormone (ACTH) produced by the anterior pituitary gland, functions as a melanocortin (MC) receptor antagonist. It effectively inhibits α-melanocyte-stimulating hormone (α-MSH)-induced excessive grooming behavior in rats [1].

Ritlecitinib, also known as PF-06651600, is a potent and selective JAK3 inhibitor. PF-06651600 is a potent and low clearance compound with demonstrated in vivo efficacy. The favorable efficacy and safety profile of this JAK3-specific inhibitor PF-06651600 led to its evaluation in several human clinical studies. JAK3 was among the first of the JAKs targeted for therapeutic intervention due to the strong validation provided by human SCID patients displaying JAK3 deficiencies.

MC-4R Agonist 1 is an agonist of human melanocortin-4 receptor (MC-4R) and can be used in the research of sexual dysfunction, obesity, and diabetes.

SNT-207858 is a selective, blood brain barrier penetrating, potent and orally active antagonist of melanocortin-4 (MC-4) receptor. SNT207858 has an IC50 of 22 nM (binding) and 11 nM (function) on the MC-4 receptor.

SNT-207707 is a potent, selective and orally active antagonist of melanocortin MC-4 receptor(IC50 of 8 nM (binding) and 5 nM (function) on the MC-4 receptor).

MC-Val-Cit-PAB is a cathepsin cleavable ADC linker that is used for making antibody-drug conjugate. FDA approved drugs such as brentuximab vedotin use this linker.

SNT-207858 free base is a selective, blood brain barrier penetrating, potent and orally active antagonist of melanocortin-4 (MC-4) receptor(IC50 of 22 nM (binding) and 11 nM (function), on the MC-4 receptor).

MC-4R Agonist 2 (Example 1), a melanocortin 4 receptor (MC4R) agonist, is employed in the research of conditions such as obesity, diabetes, inflammation, and erectile dysfunction [1].

MC4 is a first-in-class inhibitor of ribosomal RNA synthesis with antimicrobial activity against Staphylococcus aureus.

Acetyl-ACTH (4-24) (human, bovine, rat), a proopiomelanocortin (POMC) peptide fragment, functions as an agonist at the MC-1 receptor [1]. This compound encompasses a sequence present in adrenocorticotrophin (ACTH), which serves as the precursor for α-MSH, illustrating its significant role in the POMC peptide family.