LM10

Catalog No.S8368 Batch:S836803

Technical Data

Formula	C₁₁H₈FN₅
Molecular Weight	229.21	CAS No.	1316695-35-8
Solubility (25°C)*	In vitro	DMSO	46 mg/mL (200.68 mM)
		Ethanol	20 mg/mL (87.25 mM)
		Water	˂1 mg/mL
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

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.

Targets

mTDO ^[1]
(in P815B cells)

2 μM

In vitro

LM10 (Ki=5.6 μM) displays an excellent selectively prolfile and does not display any inhibitory potency on IDO^[1].

In vivo

LM10 has high plasma concentration and oral bioavailability in mouse. The plasma concentration of LM10 after oral administration of 160 mg/kg/day is between 20 and 40 μg/mL (87-175 μM), a concentration about 40 times above the IC50 measured in the cellular assay performed with the physiological concentration of plasma tryptophan. Systemic treatment of immunized mice with LM10 at 160 (mg/kg)/day prevents the growth of TDO-expressing P815 tumor cells. Moreover, mice treated with LM10 do not show obvious signs of toxicity^[1]^[2].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines P815B cells Concentrations 2, 20, or 200 μM Incubation Time 8 h Method The assay is performed in 96-well flat bottom plates seeded with 2×10⁵ cells in a final volume of 200 μL. To determine the TDO inhibitory potency of the synthesized molecules, the cells are incubated for 8 h at 37℃ in HBSS (Hanks' balanced salt solution), supplemented with 80 μM L-tryptophan and 2, 20, or 200 μM of the studied compound. To determine the IC50, the cells are incubated for 8 h at 37℃ in HBSS supplemented with 80 μM L-tryptophan and a titration of the compound ranging from 0.3 to 80 μM or from 1.5 to 400 μM. The plates are then centrifuged for 10 min at 300g, and 150 μL of the supernatant is collected. The wells are preserved for cell viability evaluation. The supernatant is analyzed by HPLC to measure the concentration of residual tryptophan and produced kynurenine, based on the retention time and the UV absorption (280 nm for tryptophan, 360 nm for kynurenine).
Animal Study:^{^[1]}	Animal Models DBA/2 mice Dosages 160 mg/kg Administration oral administration

Cell Assay:^{^[1]}

Cell lines
P815B cells
Concentrations
2, 20, or 200 μM
Incubation Time
8 h
Method
The assay is performed in 96-well flat bottom plates seeded with 2×10⁵ cells in a final volume of 200 μL. To determine the TDO inhibitory potency of the synthesized molecules, the cells are incubated for 8 h at 37℃ in HBSS (Hanks' balanced salt solution), supplemented with 80 μM L-tryptophan and 2, 20, or 200 μM of the studied compound. To determine the IC50, the cells are incubated for 8 h at 37℃ in HBSS supplemented with 80 μM L-tryptophan and a titration of the compound ranging from 0.3 to 80 μM or from 1.5 to 400 μM. The plates are then centrifuged for 10 min at 300g, and 150 μL of the supernatant is collected. The wells are preserved for cell viability evaluation. The supernatant is analyzed by HPLC to measure the concentration of residual tryptophan and produced kynurenine, based on the retention time and the UV absorption (280 nm for tryptophan, 360 nm for kynurenine).

Animal Study:^{^[1]}

Animal Models
DBA/2 mice
Dosages
160 mg/kg
Administration
oral administration

References

Selleck's LM10 has been cited by 3 publications

Tumor-associated nonmyelinating Schwann cell-expressed PVT1 promotes pancreatic cancer kynurenine pathway and tumor immune exclusion [ Sci Adv, 2023, 9(5):eadd6995]	PubMed: 36724291
Tryptophan 2, 3‑dioxygenase promotes proliferation, migration and invasion of ovarian cancer cells [ Mol Med Rep, 2021, 23(6)445]	PubMed: 33846800
Tryptophan 2,3-dioxygenase inhibitory activities of tryptanthrin derivatives [Zhang S, et al. Eur J Med Chem, 2018, 160:133-145]	PubMed: 30321802

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.