PD-L1/HDAC6-IN-1 TFA 

PD-L1/HDAC6-IN-1 TFA is an orally active dual inhibitor of PD-L1 and HDAC6, with IC₅₀ values of 26.8 nM and 78 nM, respectively. PD-L1/HDAC6-IN-1 TFA binds to human and murine PD-L1 proteins with high affinity, while it reduces STAT3 phosphorylation and downregulates PD-L1 expression by inhibiting HDAC6, thus blocking the PD-1/PD-L1 interaction. PD-L1/HDAC6-IN-1 TFA exhibits potent anti-tumor activity in a mouse melanoma model. PD-L1/HDAC6-IN-1 is suitable for research on tumor immune regulation related to melanoma^[1].

PD-L1/HDAC6-IN-1 (HP29) (0.1-2.0 μM; 12 h) TFA upregulates the level of acetylated α-tubulin in B16-F10 cells and Jurkat cells^[1].
PD-L1/HDAC6-IN-1 (0.1-2.0 μM; 24 h) TFA downregulates the expression of p-STAT3 and PD-L1 in B16-F10 cells^[1].
PD-L1/HDAC6-IN-1 TFA shows negligible cytotoxicity against B16-F10, HepG2, MCF-7 and Jurkat cells^[1].
PD-L1/HDAC6-IN-1 (0.01-10 μM; 48 h) TFA shows negligible cytotoxicity against HepG2 cells and Jurkat T cells, while dose-dependently increasing the mortality of HepG2 cells co-cultured with Jurkat T cells with an IC₅₀ of 3.4 μM^[1].
PD-L1/HDAC6-IN-1 TFA dose-dependently activates luciferase activity in PD-1/PD-L1 NFAT reporter assay (EC₅₀ = 3.15 μM)^[1].
PD-L1/HDAC6-IN-1 TFA binds to human PD-L1 and murine PD-L1 with K_D values of 179 nM and 73 nM in the ITC assay, and 464 nM and 55.3 nM in the SPR assay, respectively^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

PD-L1/HDAC6-IN-1 (HP29) (20 mg/kg; i.p., once daily for 14 days) TFA significantly suppresses tumor growth with a tumor growth inhibition (TGI) rate of 65.5% in the B16-F10 melanoma model, induces no obvious body weight loss or systemic toxicity, markedly elevates the percentages of tumor-infiltrating CD3⁺CD4⁺ and CD3⁺CD8⁺ lymphocytes, and significantly reduces PD-L1 protein expression while increasing acetylated α-tubulin levels in tumor tissues^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

561.59

C₂₉H₃₄F₃N₃O₅

Solid

CC1=C(C=CC=C1C2=CC=CC=C2)C3=NC(OC)=C(C=C3)CNCCCCCCC(NO)=O.OC(C(F)(F)F)=O

Room temperature in continental US; may vary elsewhere.

• [1]. Hu Z, et al. Discovery of Novel and Highly Potent Dual PD-L1/Histone Deacetylase 6 Inhibitors with Favorable Pharmacokinetics for Cancer Immunotherapy. J Med Chem. 2025;68(5):5426-5454.  [Content Brief]