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Chemical Structure| 1316695-35-8 Chemical Structure| 1316695-35-8

Structure of LM10
CAS No.: 1316695-35-8

Chemical Structure| 1316695-35-8

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LM10 is a selective tryptophan 2,3-dioxygenase (TDO) inhibitor with IC50 values of 0.62 and 2 μM for human and mouse TDO, respectively.

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Product Citations

Product Citations

Hu, Simeng ; Lu, Huanzi ; Xie, Wenqiang ; Wang, Dikan ; Shan, Zhongyan ; Xing, Xudong , et al.

Abstract: Characterization of the dynamic change in the immunological landscape during malignant transformation from precancerous lesions to cancerous lesions in squamous cell carcinoma (SCC) is critical for the application of immunotherapy. Here, we performed single-cell RNA-Seq (scRNA-Seq) of 131,702 cells from 13 cancerous tissues of oral squamous cell carcinoma (OSCC), 3 samples of precancerous oral leukoplakia, and 8 adjacent normal samples. We found that tumor-infiltrating CD4+ and CD8+ T cells were functionally inhibited by immunosuppressive ligands expressed on various types of myeloid cells or neutrophils in the process of oral carcinogenesis. Notably, we identified a subset of myofibroblasts that exclusively expressed tryptophan 2,3-dioxygenase (TDO2). These TDO2+ myofibroblasts were located distally from tumor nests, and both CD4+ and CD8+ T cells were enriched around them. Functional experiments revealed that TDO2+ myofibroblasts were more likely to possess the ability for chemotaxis toward T cells but induced the transformation of CD4+ T cells into Tregs and caused CD8+ T cell dysfunction. We further showed that use of the TDO2 inhibitor LM10 attenuated the inhibitory states of T cells, restored the T cell antitumor response, and prevented the progression of OSCC malignant transformation in murine models. Our study reveals a multistep transcriptomic landscape of OSCC and demonstrates that TDO2+ myofibroblasts are potential targets for immunotherapy.

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Product Details of LM10

CAS No. :1316695-35-8
Formula : C11H8FN5
M.W : 229.21
SMILES Code : FC1=CC2=C(C=C1)C(/C=C/C3=NN=NN3)=CN2
English Name :(E)-3-(2-(1H-Tetrazol-5-yl)vinyl)-6-fluoro-1H-indole
MDL No. :MFCD26097257
InChI Key :JDBSZVDIUIRSDG-DAFODLJHSA-N
Pubchem ID :135743630

Safety of LM10

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Myc−/− cells 5 µM overnight Limited nuclear translocation of AHR Genes Dev. 2019 Sep 1;33(17-18):1236-1251.
TDO2+ myofibroblasts 5 μM 3 days Attenuated the inhibitory states of T cells, restored the T cell antitumor response J Clin Invest. 2022 Oct 3;132(19):e157649.
Rat brain endothelial cells 100 nM 4 days To evaluate the effect of LM10 on BBB integrity, found that LM10 significantly increased TEER and reversed IL-1β-induced BBB dysfunction J Neuroinflammation. 2016 Feb 1;13:25.
Fibroid explants 50μM 48 hours To investigate the effect of 680C91 on gene expression in fibroid explants, results showed that 680C91 blocked tryptophan-induced expression of CYP1B1, TGF-β3, FN1, CDK2, E2F1, IL8, and SPARC mRNA Fertil Steril. 2024 Apr;121(4):669-678.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
C57BL/6NCrl mice Rotenone-induced Parkinson’s disease mouse model Oral 12.5, 25, 50 mg/kg Once daily for 35 days Evaluation of LM10 effects on rotenone-induced motor and cognitive dysfunction, dopaminergic cell loss, neuroinflammation, and intestinal dysfunction. Results showed that LM10 improved motor function, reduced dopaminergic cell loss in the substantia nigra, decreased neuroinflammatory markers, and improved intestinal transit and colon length. FEBS J. 2021 Jul;288(14):4311-4331
C57BL/6 mice 4NQO-induced oral cancer model Oral gavage 160 mg/kg Once daily for 4 weeks Prevented the progression of OSCC malignant transformation J Clin Invest. 2022 Oct 3;132(19):e157649.

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4.36mL

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0.44mL

21.81mL

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2.18mL

43.63mL

8.73mL

4.36mL

 

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