Art. -Nr.: HY-184203

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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Formel: C₁₆H₁₃N₇O₄
Molecular Weight:367.32

Speicherung:

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

SM-06-09 Chemical Structure

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
Reinheit & Dokumentation
Verweise
Calculators
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

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)

Alle HDAC Isoform-spezifische Produkte anzeigen :

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.

Real Time qPCR^[1]

Cell Line:

Mouse bone marrow-derived macrophages (BMDMs)
Concentration:

0.5, 1, 2.5, 5, and 10 μM
Incubation Time:

16 h after polarization
Result:

Increased expression of M1-associated genes Tnf and Nos2 and decreased expression of M2-associated genes Arg1 and Fizz1.

Cell Viability Assay^[1]

Cell Line:

RAW264.7 macrophages
Concentration:

10, 5, 2.5, 1.25, 0.625, 0.312 and 0.156 μM
Incubation Time:

24 h
Result:

Displayed minimal cytotoxicity (<10%) throughout the tested concentration range.

Cell Migration Assay ^[1]

Cell Line:

UBC-GFP mouse BMDMs and SM1 melanoma cells
Concentration:

2.5 μM pretreatment
Incubation Time:

24 h
Result:

Significantly reduced migration of M2-like macrophages toward SM1 melanoma cells.

Cell Proliferation Assay^[1]

Cell Line:

Murine splenic T cells cocultured with BMDMs (M1-polarized)
Concentration:

Effective concentrations consistent with prior macrophage treatments (primarily 5 μM)
Incubation Time:

72 h
Result:

Significantly increased CD8⁺ T-cell proliferation following coculture with SM-06-09-treated M1 macrophages.

Western Blot Analysis^[1]

Cell Line:

Mouse bone marrow-derived macrophages (BMDMs)
Concentration:

0.5, 1, 2.5, 5, and 10 μM
Incubation Time:

24 h after polarization
Result:

Reduced Arg1 protein expression and increased or maintained iNOS protein expression.

Western Blot Analysis^[1]

Cell Line:

Mouse bone marrow-derived macrophages (BMDMs)
Concentration:

0.5, 1, 2.5, 5, and 10 μM
Incubation Time:

Up to 120 h
Result:

Maintained elevated acetylated α-tubulin levels for up to 120 h following a single treatment.

Western Blot Analysis^[1]

Cell Line:

RAW264.7 macrophages
Concentration:

0.5, 1, 2.5, 5, and 10 μM
Incubation Time:

24 h
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 (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.

Animal Model:

SM1 murine melanoma model (6-8 weeks, female, C57BL/6)^[1]
Dosage:

25 mg/kg
Administration:

intraperitoneal iniections (i.p,), every other day for 10-23 days
Result:

Reduced tumor growth significantly compared to the vehicle group.
Reduced the proportion of M2-like macrophages within tumors.

Animal Model:

SM1 murine melanoma model (6-8 weeks, female, C57BL/6)^[1]
Dosage:

25, 50, 100 mg/kg
Administration:

Oral gavage (p.o.), daily for 2 weeks
Result:

Did not induce obvious body weight loss or observable organ toxicity.

Animal Model:

SM1 murine melanoma model (6-8 weeks, female, C57BL/6; combined with 10 mg/kg anti-PD-1)^[1]
Dosage:

100 mg/kg
Administration:

Oral gavage (p.o.), once daily for 11-25 days
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.

Related Protocols :

Chemical Information

Molecular Weight 367.32
Formel C₁₆H₁₃N₇O₄
SMILES

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

Room temperature in continental US; may vary elsewhere.
Speicherung

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

Reinheit & Dokumentation

Handling Instructions (2659 KB)

Verweise

[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. [Content Brief]

Calculators

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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SM-06-09

Alle HDAC Isoform-spezifische Produkte anzeigen