fap inhibitor

BR102910 (4-Thiazolecarboxamide, N-[2-[(2S)-2-cyano-4,4-difluoro-1-pyrrolidinyl]-2-oxoethyl]-2-[(3,4-dichlorophenyl)methyl]-) 是一种选择性的成纤维细胞活化蛋白（FAP）的抑制剂。

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

FAPI-2 是一种基于放射性示踪剂 FAP 标记的成纤维细胞活化蛋白特异性抑制剂，具有抗癌活性，可用于研究胰腺癌。

FAPI-4 是一种成纤维细胞激活蛋白 (FAP) 抑制剂，是FAPI配体，在原发性肝癌肝细胞癌（HCC）的PET成像中显示出强烈的肝脏摄取作用，常用于 PET 成像，可用于研究癌症。

FAPI-mFS，作为一种不可逆的成纤维细胞活化蛋白 (FAP) 抑制剂，通过与FAP形成共价结合来提高在癌细胞中的摄取与滞留。此化合物在标记放射性68Ga或177Lu后，可应用于癌症的成像与治疗领域。

3BP-3580 是一种靶向成纤维细胞活化蛋白 (FAP) 的抑制剂 (pIC50: 8.6)，适用于癌症研究。

DOTA-NI-FAPI-04 是一种强效的FAP抑制剂 (IC50= 7.44 nM)，通过结合FAP靶向机制和携带缺氧敏感基团 (硝基咪唑)，显著增加了在肿瘤内的摄取和滞留。该化合物利用 DOTA 螯合金属同位素(如68Ga和177Lu)，可生成放射性探针([68Ga]Ga/DOTA-NI-FAPI-04 和 [177Lu]Lu/DOTA-NI-FAPI-04)，推动肿瘤诊断与治疗剂研究。在癌症成像以及肿瘤微环境研究中，它具有双重靶向潜力，尤其适合研究肿瘤基质和低氧区域协同效应的应用。

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) 是一种FAP抑制剂，IC50值为1.7 nM。FAP-IN-5 可用于研究肿瘤正电子发射断层扫描 (PET) 成像。

QI-18 是一种成纤维细胞激活蛋白 (FAP) 的抑制剂，其IC50值为0.50 nM，活性是UAMC-1110 (IC50 3.25 nM) 的6.5倍。QI-18 可用于合成高肿瘤选择性和高剂量的放射性示踪剂，应用于肿瘤的诊断和治疗。

DOTAGA-FAP-2286-ALB 是 Rofapitide tetraxetan 的衍生物，是一种靶向成纤维细胞活化蛋白 (FAP) 的选择性抑制剂，IC50为67.5 nM。通过与白蛋白的相互作用，DOTAGA-FAP-2286-ALB 增强了肿瘤中的滞留时间，延长了在血液中的循环时间，并提高了放射性金属复合物的稳定性（如111In和225Ac）。该化合物有潜力应用于FAP阳性实体瘤的放射性核素治疗 (TRT) 研究。

PNT6555 是一种成纤维细胞活化蛋白-α (FAP) 抑制剂，具有抗肿瘤活性，可用于FAP阳性肿瘤的显像。

FAP-IN-4 (Comp 10) 是成纤维细胞活化蛋白 (FAP) 的抑制剂，同时也是靶向FAP的18F标记PET示踪剂，可用于肿瘤研究。

FAP-IN-6 (Compound 21) 是一种选择性FAP抑制剂，具有13 pM的IC50，并显示出良好的代谢稳定性。18F标记的FAP-IN-6能作为正电子发射断层扫描 (PET) 示踪剂，用于癌症微环境研究。

FAPI-P8PN 是一种成纤维细胞活化蛋白 (FAP) 抑制剂，具有IC50=3.6 nM的特性。有望用于研究FAP过表达的实体瘤。

OncoFAP-GlyPro-MMAE 是一种 FAP 小分子药物偶联物 (SMDC)，其 IC50 为 0.49 nM。由 FAP 配体 OncoFAP、微管蛋白 (Tubulin) 抑制剂 (MMAE) 和连接子组成，OncoFAP-GlyPro-MMAE 用于癌症研究，如肾癌。

DOTA-ALB-01 是一种结合白蛋白的FAP抑制剂 (FAPI) 配体。68Ga 或177Lu 标记的DOTA-ALB-01 具有很高的FAP结合亲和力，并增强了肿瘤的摄取和滞留能力。DOTA-ALB-01 可用于癌症，特别是晚期癌症的PET/CT和SPECT/CT成像。

DOTA-ALB-02 是一种白蛋白结合的FAP抑制剂 (FAPI) 配体。经过177Lu 标记后，DOTA-ALB-02 具有很强的FAP结合亲和力，能够提高肿瘤的摄取和滞留，并展现出显著的肿瘤/非靶标比率。DOTA-ALB-02 可用于癌症，尤其是晚期癌症的PET/CT 和 SPECT/CT 成像。

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.

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 是 fibroblast activation protein（FAP）抑制剂，也是 FAPI-4 的结构类似物。NOTA-FAPI-4 被用于研究 FAP 过表达相关疾病的诊断和研究，包括作为正电子发射断层成像（PET）示踪剂，用于非侵入性成像及治疗反应监测。

FAP-PI3KI1 是一种成纤维细胞活化蛋白 (FAP) 靶向 PI3K 抑制剂，可选择性靶向表达 FAP 的人特发性肺纤维化 (IPF)细胞并有效抑制胶原蛋白合成，减少胶原蛋白沉积。

Rofapitide tetraxetan(FAP-2286)是一种高亲和力和选择性的FAP（成纤维细胞活化蛋白）抑制剂和DOTA-pseudopeptide（假肽），IC50=1.3~2.2 nM。FAP-2286靶向肿瘤微环境，可以进行放射性标记（如68 Ga）并用于正电子发射断层扫描（PET）成像。