SM-06-09 

SM-06-09 is a potent, highly selective, orally active tetrazolone-based HDAC6 inhibitor with an IC₅₀ value of 0.49 nM. SM-06-09 promotes tumor-associated macrophage (TAM) polarization toward an antitumor M1-like phenotype and enhances macrophage phagocytosis, antigen presentation, and T-cell activation. SM-06-09 remodels the tumor immune microenvironment, exhibits antitumor activity in melanoma models, and enhances the efficacy of anti-PD-1 immune checkpoint blockade^[1].

SM-06-09 (Compound 3m) potently inhibits HDAC6 with an IC₅₀ value of 0.49 nM and exhibits good selectivity over HDAC10 (IC₅₀=16.9 nM), HDAC2 (IC₅₀=173 nM), HDAC3 (IC₅₀=258 nM), HDAC1 (IC₅₀=338 nM), and HDAC8 (IC₅₀=453 nM)^[1].
SM-06-09 (0.15-10 μM) dose-dependently inhibits total HDAC activity in RAW264.7 macrophages, achieving approximately 85% inhibition at 10 μM^[1].
SM-06-09 (0.5-10 μM; 24 h) increases acetylated α-tubulin levels in RAW264.7 macrophages, confirming cellular HDAC6 inhibition^[1].
SM-06-09 (0.15-20 μM; 24 h) exhibits minimal cytotoxicity in RAW264.7 cells, with less than 10% growth inhibition at the highest tested concentration^[1].
SM-06-09 (5 μM; 16 h after polarization) promotes M1 polarization in bone marrow-derived macrophages (BMDMs), upregulates Tnf and Nos2 expression, and downregulates Arg1 and Fizz1 expression. SM-06-09 (5 μM) also decreases Arg1 protein levels while maintaining iNOS expression^[1].
SM-06-09 (5 μM) induces transcriptional reprogramming in M1- and M2-polarized BMDMs, downregulates M2-associated genes including Arg1 and Retnla, and upregulates pro-inflammatory genes such as Cxcl3, Cxcl5, and C3. SM-06-09 enriches pathways involved in antigen presentation, T-cell activation, and TNF/IFN inflammatory signaling while suppressing pathways associated with extracellular matrix organization and mesenchymal differentiation^[1].
SM-06-09 (5 μM) induces sustained HDAC6 inhibition in BMDMs, with elevated acetylated α-tubulin levels persisting for up to 120 h following a single treatment. SM-06-09 enhances macrophage-mediated phagocytosis of SM1 melanoma cells, suppresses migration of M2-like macrophages (2.5 μM; 24 h), and promotes antigen presentation as well as CD8⁺ T-cell activation and proliferation^[1].

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

SM-06-09 (Compound 3m) (25 mg/kg; intraperitoneal injection; every other day for 10-23 days) significantly inhibits tumor growth and reprograms the tumor microenvironment in a C57BL/6 mouse SM1 melanoma model, with a marked reduction in intratumoral M2-like macrophages^[1].
SM-06-09 (25, 50, 100 mg/kg; oral gavage; once daily for 2 weeks) shows no obvious body weight loss or organ toxicity in the C57BL/6 SM1 melanoma model, indicating favorable in vivo safety and tolerability^[1].
SM-06-09 (100 mg/kg; oral gavage; once daily for 11-25 days) in combination with an anti-PD-1 antibody (10 mg/kg; intraperitoneal injection; twice weekly) significantly enhances antitumor efficacy and improves the tumor immune microenvironment in a C57BL/6 mouse SM1 melanoma model. The combination increases intratumoral CD45⁺ immune cells and F4/80⁺ macrophage infiltration, elevates the proportion of M1-like macrophages and the M1/M2 ratio, and enhances CD8⁺ T cell infiltration, with increased effector memory and central memory CD8⁺ T cell populations^[1].

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

367.32

C₁₆H₁₃N₇O₄

O=C(NO)C1=NOC(CCN2C(N(C3=CC(C=CC=C4)=C4N=C3)N=N2)=O)=C1

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Gajendran N, et al. Macrophage-Centric Phenotypic Screening Identifies Tetrazolone-Based HDAC6 Inhibitors That Reprogram the Tumor Immune Microenvironment and Improve Immune Checkpoint Blockade. J Med Chem. 2026 Jun 11;69(11):12870-12897.