TNG260 

TNG260 is a selective, orally effective inhibitor of HDAC1 and CoREST complex, with a 10-fold selectivity for HDAC1 over HDAC3 and a 500-fold selectivity for CoREST complex over NuRD and Sin3 complex. TNG260 reshapes the tumor immune microenvironment, reduces immunosuppressive neutrophil infiltration, promotes effector T cell recruitment, and reverses anti-PD-1 resistance caused by STK11 deficiency by inhibiting the activity of the CoREST-HDAC1 complex. TNG260 induces durable tumor regression in combination with α-PD1 in MC38 tumor-bearing mice with STK11 mutations, and has lower toxicity to bone marrow cells than non-selective HDAC inhibitors^[1].

TNF260 assists anti-PD-1 immunotherapy and sensitizes STK11 mutant non-small cell carcinoma (NSCLC) tumors to anti-PD-1 immunotherapy such as Pembrolizumab (HY-P9902) by targeting the CoREST complex through epigenetic reprogramming^[2].
TNF260 also promotes the expression of genes encoding pro-inflammatory factors and inhibits the expression of cell cycle and mitotic checkpoint-related genes in KRAS/STK11 mutant lung cancers. However, it has no significant effect on STK11 wild-type KRAS/P53 mutant lung cancer cells^[2].

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

TNG260 synergizes with anti-PD-1 therapy to inhibit KRAS/STK11 mutant NSCLC tumor growth in STK11 mutant NSCLC allografts and genetically engineered mouse models (GEMMs) without significant toxicity to mice. TNG260 also synergizes with anti-PD-1 therapy to increase markers of macrophages, neutrophils, and dendritic cells^[2].

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

383.44

C₂₀H₁₈FN₃O₂S

2935964-98-8

Solid

White to yellow

NC1=CC=C(C2=CC=C(F)C=C2)C=C1NC(C3=CC=C([S@](=O)(C)=N)C=C3)=O

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Ahronian L, et al. TNG260, a CoREST-selective deacetylase inhibitor, reverses anti-PD1 resistance driven by loss of STK11[J]. J Immunother, 2022, 10(2): A1-A1595.

  [2]. Patel Ayushi, et al. TNG260, a small molecule CoREST inhibitor, sensitizes STK11-mutant NSCLC to anti-PD1 immunotherapy. Cancer Research 84.6_Supplement (2024): 3916-3916.