fibroblast activation protein (fap)

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.

FAP targeting peptide for FXX489 is the peptide component of FXX489. FXX489 is a targeting ligand that can specifically recognize and bind to fibroblast activation protein (FAP).

FAPI-2 is a specific inhibitor of fibroblast-activated protein based on the radiotracer FAP labeling. It has anticancer activity and can be used in the study of pancreatic cancer.

FAPI-4 FAPI-4 is a fibroblast activating protein (FAP) inhibitor, a FAPI ligand, which shows strong liver uptake in PET imaging of primary liver cancer hepatocellular carcinoma (HCC) and is commonly used in PET imaging for the study of cancer.

FAPI-mFS, an irreversible fibroblast activation protein (FAP) inhibitor, enhances uptake and retention in cancer cells through its covalent binding properties with FAP. When labeled with radioactive 68Ga or 177Lu, FAPI-mFS can be utilized for cancer imaging and therapy.

3BP-3580 is an inhibitor of fibroblast activation protein (FAP) with a pIC50 value of 8.6, utilized in cancer research.

ARI-3099 inhibits fibroblast activation protein, alpha (FAP).

FAPI-46 is a quinoline-derived radiotracer that specifically targets fibroblast activation protein (FAP). It exhibits enhanced tumor uptake and extended accumulation in tumor tissues, rendering it suitable for diverse cancer imaging applications.

BR103354 is a novel fibroblast activation protein (FAP) inhibitor with anti-diabetic and anti-steatotic effects. BR103354 inhibited FAP with an IC50 value of 14 nM, showing high selectivity against dipeptidyl peptidase (DPP)-related enzymes and prolyl oligopeptidase (PREP). BR103354 exhibited good pharmacokinetic properties as evidenced by oral bioavailability of 48.4% and minimal hERG inhibition. Single co-administration of BR103354 with hFGF21 reduced nonfasting blood glucose concentrations, in association with increased intact form of hFGF21 in ob ob mice. BR103354 acts as an effective FAP inhibitor in vitro and in vivo, thereby demonstrating its potential application as an anti-diabetic and anti-NASH agent.

NOTA-FAPI-4 is an analogue of FAPI-4 and a fibroblast activation protein (FAP) inhibitor. NOTA-FAPI-4 is useful in the diagnosis or treatment of a disease characterized by overexpression of fibroblast activation protein (FAP). NOTA-FAPI-4 can be used as a PET tracer for detection of diseases or disorders related to fibroblast activation protein.

Suc-Gly-Pro-AMC, a fibroblast activation protein (FAP)-specific substrate, facilitates the examination of FAP activity [1].

FSDD0I, an albumin-binding fibroblast activation protein (FAP) ligand, can be labeled with 68Ga and 177Lu for use in single photon emission computed tomography (SPECT) imaging [1].

FSDD1I, an albumin-binding fibroblast activation protein (FAP) ligand, can be tagged with 68 Ga and 177 Lu for use in single photon emission computed tomography (SPECT) imaging [1].

FSDD3I, an albumin-binding fibroblast activation protein (FAP) ligand, can be tagged with isotopes 68Ga and 177Lu for use in single photon emission computed tomography (SPECT) imaging [1].

FAP-2286 is a peptidic macrocycle that binds to the fibroblast activation protein (FAP) and is linked to the chelator DOTA, facilitating its role as a tumor imaging agent in positron emission tomography (PET) research. Exhibiting strong affinity for the human FAP protein with a dissociation constant (Kd) of 1.1 nM, FAP-2286 demonstrates significant antitumor activity, as referenced in [1] [2].

FAP-2286 acetate, a conjugate of a fibroblast activation protein (FAP)-binding peptide, exhibits antitumor activity [1]. It can be labeled with radionuclides for diagnostic purposes.

FAP-IN-2 TFA is a 99mTc-labeled, isonitrile-containing derivative inhibitor of fibroblast activation protein (FAP), used for tumor imaging [1].

SP-13786 is an inhibitor of fibroblast activation protein (FAP) and prolyl oligopeptidase (PREP) with IC50 values ​​of 3.2 nM and 1.8 μM, respectively.

FAP-IN-1 is a fibroblast activation protein (FAP) inhibitor with an IC50 of 3.3 nM, used for cancer research [1].

FAP-IN-2 is a 99mTc-labeled, isonitrile-containing derivative of a fibroblast activation protein (FAPI) inhibitor suitable for tumor imaging [1].

FAPI-2 TFA, a fibroblast activation protein (FAP) inhibitor, is potentially applicable in cancer research [1].

FAP Ligand 1 (FL), a high-affinity small molecule targeting fibroblast activation protein (FAP), facilitates the delivery of conjugated therapeutics to FAP-expressing fibroblasts and enables radiographic imaging of select tumors [1].

ARI-3144, a substrate for fibroblast activation protein (FAP), serves as a FAP-activated proteasome inhibitor, making it valuable for solid tumor research [1].

SB03178 is an inhibitor of fibroblast activation protein-alpha (FAP) that can be conjugated with DOTA for use in cancer research [1].