fap inhibitor

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.

FAPI-34, a fibroblast-activating protein (FAP) inhibitor, boasts advantageous pharmacokinetic and biochemical attributes.

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

Fapi-2 is a fibroblast activated protein (FAP) inhibitor used in cancer research.

BR102910 (4-Thiazolecarboxamide, N-[2-[(2S)-2-cyano-4,4-difluoro-1-pyrrolidinyl]-2-oxoethyl]-2-[(3,4-dichlorophenyl)methyl]-) is a selective inhibitor of fibroblast activated protein (FAP).

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

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

NH2-UAMC1110 TFA, a derivative of the fibroblast activation protein (FAP) inhibitor UAMC1110, serves as a precursor in the formation of FAPI-QS, a chelating agent crucial for creating radiotracers with high tumor selectivity and potency for tumor diagnosis and therapy [1] [2].

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.

SP-13786 (UAMC-1110) is an inhibitor of fibroblast activation protein (FAP) (IC50 : 3.2 nM); also inhibits prolyl oligopeptidase (PREP) ( IC50 : 1.8 μM).

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.

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.

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

FAP-PI3KI1, a fibroblast-activated protein (FAP)-targeted PI3K inhibitor, selectively targets FAP-expressing human idiopathic pulmonary fibrosis (IPF) cells. It effectively inhibits collagen synthesis and reduces collagen deposition [1].

Ac-Gly-BoroPro is a selective FAP inhibitor (Ki: 23 nM).