fibroblast activation protein

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.

Trimethylamine N-oxide (TMAO) is a gut microbiota-dependent metabolite derived from dietary choline, betaine, and carnitine. It induces inflammation by activating the ROS/NLRP3 inflammasome and promotes fibroblast differentiation through the activation of the TGF-β/Smad2 signaling pathway. TMAO is commonly used to induce cardiac fibrosis models.

The FAP-targeting peptide for FXX489 constitutes the peptide moiety of FXX489, suitable for biochemical assays and drug synthesis studies. FXX489 is a fibroblast activation protein (FAP)-targeting ligand employed in radioligand therapy (RLT) for multiple cancers.

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.

ML334 (LH601A) is a transmembrane and potent NRF2 activator that inhibits Keap1-NRF2 protein interactions to ameliorate myocardial infarction-induced cardiac fibrosis by inhibiting cardiac fibroblast activation and proliferation.

DOTAGA.(SA.FAPi)2 TFA is an effective dimeric fibroblast activation protein inhibitor (FAPi). This compound holds potential for use in cancer diagnostic research.

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.

QI-18 is a fibroblast activation protein (FAP) inhibitor with an IC50 value of 0.50 nM, offering a 6.5-fold increase in activity compared to UAMC-1110 (IC50 3.25 nM). It can be utilized in the synthesis of highly tumor-selective and high-dose radiotracers for the diagnosis and treatment of tumors.

FAP-targeting peptide-PEG2 conjugate (Example A1) is the polypeptide and linker conjugate component of Unlabeled FXX489. Unlabeled FXX489 serves as a ligand targeting fibroblast activation protein (FAP).

DOTAGA-FAP-2286-ALB is a derivative of Rofapitide tetraxetan. It functions as a selective inhibitor of fibroblast activation protein (FAP) with an IC50 value of 67.5 nM. By interacting with albumin, DOTAGA-FAP-2286-ALB enhances tumor retention, prolongs circulation time in the bloodstream, and improves the stability of radiometal complexes [such as 111In and 225Ac]. This compound shows promise for use in targeted radionuclide therapy (TRT) research for FAP-positive solid tumors.

PNT6555 acts as an inhibitor of fibroblast activation protein-α (FAP). It possesses anti-tumor properties and is applicable for imaging FAP-positive tumors.

FAP-IN-4 (Comp 10) is an inhibitor of fibroblast activation protein (FAP) and serves as a targeted FAP-specific radiotracer for PET imaging labeled with 18F. It is applicable in tumor research.

FAPI-JNU is a molecule that targets fibroblast activation protein (FAP). It binds specifically to FAP, which is highly expressed in the tumor microenvironment, enabling tumor imaging and diagnosis using radionuclides [68Ga]Ga or [177Lu]Lu. The compound [177Lu]Lu−FAPI−JNU can effectively target and inhibit tumor growth in mice with tumors. FAPI-JNU holds potential for research on FAP-positive tumors, such as various solid tumors.

TriOncoFAP-GlyPro-MMAE is a small molecule drug conjugate (SMDC) that targets fibroblast activation protein (FAP), with an IC50 value of 13 pmol/L. It comprises a ligand targeting FAP (TriOnco), a cleavable glycine-proline linker, and a cytotoxic payload (MMAE).

Faridoxorubicin (AVA-6000) is a prodrug that targets fibroblast activation protein alpha (FAPα). It releases active doxorubicin through FAPα-mediated cleavage, enhancing drug exposure within tumors while reducing cardiac toxicity. Faridoxorubicin holds potential for research in solid tumors, such as liver metastases from colorectal cancer.

FAPI-P8PN is an inhibitor of fibroblast activation protein (FAP) with an IC50 value of 3.6 nM. It holds potential for research involving solid tumors with overexpression of FAP.

ARI-3099 inhibits fibroblast activation protein, alpha (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.

FAPI-46 is a radiotracer for fibroblast activation protein (FAP), belonging to the class of FAP inhibitors (iFAP), and can be conjugated with labels such as 68Ga or 177Lu to serve as a tracer for FAP tumours in positron emission tomography (PET).

Talabostat mesylate (PT100) is an orally active, selective inhibitor of dipeptidyl peptidases IV (DPP4, IC50: 0.18 nM), including tumor-associated fibroblast activation protein. This agent may also stimulate the production of colony stimulating factors, such as granulocyte colony-stimulating factor (G-CSF), resulting in the stimulation of hematopoiesis.

OncoFAP acetate is the highest-affinity small organic fibroblast activation protein (FAP) ligand reported to date, exhibiting a dissociation constant of 680 pM as measured by fluorescence polarization. OncoFAP derivatives, when administered intravenously in both fluorescent and radiolabeled forms, selectively accumulate in FAP-positive tumors while sparing normal tissues, enabling OncoFAP acetate to serve as modular components for targeted therapeutic delivery of radionuclides, CAR-T cells, or cytotoxic agents in oncology studies.

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 is a fibroblast activation protein (FAP) inhibitor and structural analogue of FAPI-4. NOTA-FAPI-4 serves as a diagnostic and therapeutic tool for diseases characterized by FAP overexpression, including its application as a positron emission tomography (PET) tracer for noninvasive imaging of FAP-associated pathological conditions and monitoring of therapeutic responses.