fap inhibitor

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).

Ac-Gly-BoroPro is a selective FAP inhibitor with a Ki of 23 nM.

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.

DOTA-NI-FAPI-04 is an FAP inhibitor (IC50 = 7.44 nM). By integrating FAP targeting with hypoxia-sensitive groups (nitroimidazole), DOTA-NI-FAPI-04 significantly enhances tumor uptake and retention. Through DOTA chelation with metal isotopes (such as 68Ga and 177Lu), it forms radioactive probes ([68Ga]Ga/DOTA-NI-FAPI-04 and [177Lu]Lu/DOTA-NI-FAPI-04) useful for research in tumor diagnosis and therapeutics. This compound exhibits dual-targeting potential in cancer imaging, tumor microenvironment analysis, and radionuclide therapy, particularly in scenarios involving the interaction between tumor stroma and hypoxic regions.

AZD2389 is an effective and orally active FAP inhibitor that improves histological fibrosis and increases intact α2-AP, suitable for studying metabolic dysfunction-associated steatohepatitis.

FAP-IN-5 (Compound 4a) is an FAP inhibitor with an IC50 of 1.7 nM. It is applicable in studies involving tumor positron emission tomography (PET) imaging.

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.

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.

FAP-IN-6 (Compound 21) is a selective FAP inhibitor with an IC50 of 13 pM. It demonstrates high metabolic stability, and its 18F-labeled form serves as a tracer for positron emission tomography (PET). FAP-IN-6 is relevant for studying the cancer microenvironment.

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.

OncoFAP-GlyPro-MMAE is a FAP small molecule-drug conjugate (SMDC) with an IC50 of 0.49 nM. It is composed of the FAP ligand OncoFAP, a microtubule inhibitor (MMAE), and a linker. OncoFAP-GlyPro-MMAE can be utilized in cancer research, including studies on renal cancer.

DOTA-ALB-01 is an albumin-binding FAP inhibitor (FAPI) ligand. When labeled with 68Ga or 177Lu, DOTA-ALB-01 exhibits high FAP binding affinity and enhances tumor uptake and retention. DOTA-ALB-01 is utilized in PET/CT and SPECT/CT imaging for cancer, particularly in advanced stages.

DOTA-ALB-02 is a ligand that binds with albumin and acts as an FAP inhibitor (FAPI). When labeled with 177Lu, DOTA-ALB-02 demonstrates high affinity for FAP, enhancing tumor uptake and retention, and it has a significant tumor-to-nontarget ratio. It is used in PET/CT and SPECT/CT imaging for detecting cancer, particularly advanced stages.

FAP-IN-7 (Compound 5b) is a FAP inhibitor. The 18F-labeled version of FAP-IN-7 improves tumor retention and demonstrates high selectivity along with favorable pharmacokinetics. It can serve as a radioactive tracer for cancer PET imaging and radionuclide therapy research.

PRMT5-IN-53 is an orally active, gut-restricted PRMT5 inhibitor, exhibiting pIC50 values of ≥ 9.7 against both hPRMT5 and mPRMT5. It binds to the PRMT5:MEP50 complex with a KD of 11.3 pM. In mice, PRMT5-IN-53 effectively inhibits intestinal PRMT5, significantly reducing both the number and size of polyps while avoiding systemic hematologic toxicity such as anemia and neutropenia. This compound is applicable in colorectal cancer research, particularly for familial adenomatous polyposis (FAP).

FAPI-800CW is a near-infrared (NIR) fluorescently labeled inhibitor of fibroblast activation protein (FAP). It demonstrates specific uptake in inflamed paws of mice with collagen-induced arthritis. FAPI-800CW can be utilized for in vivo molecular imaging of FAP expression in inflammatory diseases such as rheumatoid arthritis (RA) to monitor joint inflammation and disease activity.

DPP9-IN-2 is a selective and potent orally active inhibitor of dipeptidyl peptidase 9 (DPP9), with an IC50 value of 12.9 nM. It exhibits a selectivity index of 59 for DPP8 and shows no significant inhibitory activity on related peptidases, including DPP2, DPP4, FAP, and PREP. DPP9-IN-2 can induce pyroptosis in cancer cells and demonstrates modest synergistic anti-HIV-1 activity when combined with non-nucleoside reverse transcriptase inhibitors. This compound is applicable for research in cancer and infection.

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

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.