INCB086550 (PD-1/PD-L1-IN-8)

INCB086550 (PD-1/PD-L1-IN-8) is a potent, oral, small-molecule PD-L1 inhibitor with an IC₅₀ value of 3.1nM ^[1]. INCB086550 directly blocks the binding sites of PD-1 and PD-L1, and mediates the dimerization and endocytosis of PD-L1^[2]. INCB086550 has been widely used in the humanized PD-L1 MC38 mouse model to inhibit tumor growth and for the pharmacodynamic comparison studies of different PD-L1 small molecule inhibitors^[3].

In vitro, INCB086550 treatment (1μM) for 48 hours significantly inhibited the viability of CHO-K1 cells with overexpression of TCR activator and human PD-L1 on the cell surface^[4]. Treatment with 1 µM INCB086550 for 18 hours blocked the PD-1-mediated signal transduction in CHO-K1 cells and stimulated cellular immune activation^[5].

In vivo, INCB086550 treatment (15mg/kg; twice daily for 4 weeks) via intraperitoneal injection combined with Deucravacitinib reduced the tumor volume in 4T1-hPD-L1 cell-xenograft mouse models^[6].

References:
[1] Yang D M, Kang Y W, Kim K, et al. Discovery of novel indoline derivatives as potent small molecule PD-L1 inhibitors[J]. Bioorganic & Medicinal Chemistry Letters, 2025: 130458.
[2] Chen L, Zhao X, Liu X, et al. Development of small molecule drugs targeting immune checkpoints[J]. Cancer Biology & Medicine, 2024, 21(5): 382-399.
[3] Roose H, Rekstyte-Matiene K, Stevens S, et al. 1381 Discovery of ALG-093989, a highly potent and orally bioavailable small molecule PD-L1 inhibitor for the treatment of cancers[J]. 2023.
[4] Slota A, Golebiowska-Mendroch K, Kocik-Krol J, et al. Characterization of Clinically Evaluated Small-Molecule Inhibitors of PD-L1 for Immunotherapy[J]. ACS Medicinal Chemistry Letters, 2025.
[5] Koblish H K, Wu L, Wang L C S, et al. Characterization of INCB086550: a potent and novel small-molecule PD-L1 inhibitor[J]. Cancer Discovery, 2022, 12(6): 1482-1499.
[6] Xiang H, Tu B, Feng X, et al. Dual inhibition of TYK2 and PD-L1 boosts immune response in triple negative breast cancer[J]. Anti-Cancer Drugs, 2025, 36(4): 280-289.

INCB086550 (PD-1/PD-L1-IN-8)是一种强效的口服小分子PD-L1抑制剂，IC₅₀值为3.1nM^[1]。INCB086550直接阻断PD-1和PD-L1的结合位点，并介导PD-L1的二聚化和内吞作用^[2]。INCB086550已被广泛用于人源化PD-L1 MC38小鼠模型，以抑制肿瘤生长，并用于不同PD-L1小分子抑制剂的药效比较研究^[3]。

在体外，使用1µM的INCB086550处理48小时，显著抑制了细胞表面过表达TCR激活因子和人PD-L1的CHO-K1细胞的活力^[4]。使用1µM的INCB086550处理18小时，阻断了CHO-K1细胞中PD-1介导的信号转导，并刺激了细胞免疫激活^[6]。

在体内，每日两次腹腔注射INCB086550（15mg/kg），持续4周，联合Deucravacitinib治疗，减少了4T1-hPD-L1细胞异种移植小鼠模型中的肿瘤体积^[6]。