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.
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- Fòrmula: C16H13N7O4
- Peso molecular:367.32
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
HDAC6 0.49 nM (IC50) |
HDAC10 16.9 nM (IC50) |
HDAC2 173 nM (IC50) |
HDAC3 258 nM (IC50) |
HDAC1 338 nM (IC50) |
HDAC8 453 nM (IC50) |
HDAC7 4443 nM (IC50) |
HDAC5 7602 nM (IC50) |
HDAC4 12415 nM (IC50) |
HDAC9 26035 nM (IC50) |
HDAC11 1891 nM (IC50) |
HDAC6 9.31 (pIC50) |
In Vitro
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.
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Cell Line:Mouse bone marrow-derived macrophages (BMDMs)
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Concentration:0.5, 1, 2.5, 5, and 10 μM
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Incubation Time:16 h after polarization
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Result:Increased expression of M1-associated genes Tnf and Nos2 and decreased expression of M2-associated genes Arg1 and Fizz1.
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Cell Line:RAW264.7 macrophages
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Concentration:10, 5, 2.5, 1.25, 0.625, 0.312 and 0.156 μM
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Incubation Time:24 h
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Result:Displayed minimal cytotoxicity (<10%) throughout the tested concentration range.
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Cell Line:UBC-GFP mouse BMDMs and SM1 melanoma cells
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Concentration:2.5 μM pretreatment
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Incubation Time:24 h
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Result:Significantly reduced migration of M2-like macrophages toward SM1 melanoma cells.
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Cell Line:Murine splenic T cells cocultured with BMDMs (M1-polarized)
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Concentration:Effective concentrations consistent with prior macrophage treatments (primarily 5 μM)
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Incubation Time:72 h
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Result:Significantly increased CD8+ T-cell proliferation following coculture with SM-06-09-treated M1 macrophages.
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Cell Line:Mouse bone marrow-derived macrophages (BMDMs)
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Concentration:0.5, 1, 2.5, 5, and 10 μM
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Incubation Time:24 h after polarization
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Result:Reduced Arg1 protein expression and increased or maintained iNOS protein expression.
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Cell Line:Mouse bone marrow-derived macrophages (BMDMs)
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Concentration:0.5, 1, 2.5, 5, and 10 μM
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Incubation Time:Up to 120 h
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Result:Maintained elevated acetylated α-tubulin levels for up to 120 h following a single treatment.
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Cell Line:RAW264.7 macrophages
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Concentration:0.5, 1, 2.5, 5, and 10 μM
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Incubation Time:24 h
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Result:Increased acetylated α-tubulin levels in a dose-dependent manner, indicating effective HDAC6 inhibition.
Did not significantly alter acetyl-histone H3 levels, indicating cellular selectivity toward HDAC6.
In Vivo
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.
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Animal Model:SM1 murine melanoma model (6-8 weeks, female, C57BL/6)[1]
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Dosage:25 mg/kg
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Administration:intraperitoneal iniections (i.p,), every other day for 10-23 days
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Result:Reduced tumor growth significantly compared to the vehicle group.
Reduced the proportion of M2-like macrophages within tumors.
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Animal Model:SM1 murine melanoma model (6-8 weeks, female, C57BL/6)[1]
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Dosage:25, 50, 100 mg/kg
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Administration:Oral gavage (p.o.), daily for 2 weeks
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Result:Did not induce obvious body weight loss or observable organ toxicity.
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Animal Model:SM1 murine melanoma model (6-8 weeks, female, C57BL/6; combined with 10 mg/kg anti-PD-1)[1]
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Dosage:100 mg/kg
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Administration:Oral gavage (p.o.), once daily for 11-25 days
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Result:Produced significantly greater tumor growth inhibition than monotherapies.
Increased infiltration of CD45+ immune cells and F4/80+ macrophages in tumors.
Markedly elevated the percentage of M1-like macrophages and the M1/M2 ratio.
Enhanced CD8+ T cell infiltration with increased effector memory and central memory CD8+ T cells.
Chemical Information
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Peso molecular 367.32
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Fòrmula C16H13N7O4
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SMILES
O=C(NO)C1=NOC(CCN2C(N(C3=CC(C=CC=C4)=C4N=C3)N=N2)=O)=C1
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SM-06-09 Related Classifications
HY-184203 Related Classifications
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Keywords
- SM-06-09
- HDAC
- Histone deacetylases
- HDAC6 inhibitor
- HDAC10
- tumor-associated macrophages
- TAMs
- macrophage reprogramming
- M1 macrophage polarization
- M2 macrophage
- RAW264.7
- BMDM
- bone marrow-derived macrophages
- C57BL/6 mice
- UBC-GFP mice
- melanoma
- SM1 melanoma
- tumor microenvironment
- TME
- immune checkpoint blockade
- anti-PD-1
- antigen presentation
- phagocytosis
- T-cell activation
- T-cell proliferation
- immunotherapy
- epigenetics
- acetylated α-tubulin
- Arg1
- Fizz1
- iNOS
- TNF-α
- Inhibitor
- inhibitor
- inhibit