Navoximod

製品コードS8957 バッチS895701

化学情報

	Synonyms	GDC-0919, NLG-919	Storage (From the date of receipt)	3 years -20°C powder
	化学式	C₁₈H₂₁FN₂O₂
	分子量	316.37	CAS No.	1402837-78-8
Solubility (25°C)*	体外	DMSO	63 mg/mL (199.13 mM)
		Ethanol	63 mg/mL (199.13 mM)
		Water	Insoluble
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Navoximod (GDC-0919, NLG-919) is a potent inhibitor of IDO (indoleamine-(2,3)-dioxygenase) pathway with Ki of 7 nM and EC50 of 75 nM.
in vitro	NLG919 potently blocks IDO-induced T-cell suppression and restored robust T-cell responses with ED50 of 80 nM. Similarly, using IDO-expressing mouse DCs from tumor-draining lymph nodes, NLG919 abrogated IDO-induced suppression of antigen-specific T cells (OT-I) in vitro, with ED50 of 120 nM. ^[1] NLG919 increases the cytotoxic activity of paclitaxel toward B16-F10 cells in the presence of pretreatment with interferon (IFN)-γ in vitro.^[3]
in vivo	In mice, a single oral administration of NLG919 reduces the concentration of plasma and tissue Kyn by ~ 50%. In mice bearing B16F10 tumors, NLG919 markedly enhances the antitumor responses of naive, resting pmel-1 cells to vaccination with cognate hgp100 peptide plus CpG-1826 in IFA.^[1] Immune competent mice are injected orthotopically with genetically engineered murine glioma cells and treated with GDC-0919 alone or combined with RT. GDC-0919 demonstrates potent inhibition of this node and effectively crosses the blood brain barrier. Although GDC-0919 as a single agent does not demonstrate anti-tumor activity, it has a strong potential for enhancing RT response in glioblastoma, which is further augmented with a hypofractionated regimen.^[2]

製品説明

Navoximod (GDC-0919, NLG-919) is a potent inhibitor of IDO (indoleamine-(2,3)-dioxygenase) pathway with Ki of 7 nM and EC50 of 75 nM.

in vitro

NLG919 potently blocks IDO-induced T-cell suppression and restored robust T-cell responses with ED50 of 80 nM. Similarly, using IDO-expressing mouse DCs from tumor-draining lymph nodes, NLG919 abrogated IDO-induced suppression of antigen-specific T cells (OT-I) in vitro, with ED50 of 120 nM. ^[1]

NLG919 increases the cytotoxic activity of paclitaxel toward B16-F10 cells in the presence of pretreatment with interferon (IFN)-γ in vitro.^[3]

in vivo

In mice, a single oral administration of NLG919 reduces the concentration of plasma and tissue Kyn by ~ 50%. In mice bearing B16F10 tumors, NLG919 markedly enhances the antitumor responses of naive, resting pmel-1 cells to vaccination with cognate hgp100 peptide plus CpG-1826 in IFA.^[1]

Immune competent mice are injected orthotopically with genetically engineered murine glioma cells and treated with GDC-0919 alone or combined with RT. GDC-0919 demonstrates potent inhibition of this node and effectively crosses the blood brain barrier. Although GDC-0919 as a single agent does not demonstrate anti-tumor activity, it has a strong potential for enhancing RT response in glioblastoma, which is further augmented with a hypofractionated regimen.^[2]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	the murine melanoma cell line B16-F10
	濃度	100 nM
	反応時間	12 h, 24 h, 48 h, 72 h
	実験の流れ	B16-F10 cells are diluted to 1 × 10⁵ cells/mL with DMEM supplemented with 10% FBS and seeded at 2 mL per well into 6-well plates. The culture medium is replaced with fresh growth medium with or without 25 ng/mL IFN-γ for 10–12 h after seeding. After incubation with IFN-γ for 24 h, the medium is replaced with fresh medium containing 100 nM NLG919, 3 nM PTX, or a combination of 100 nM NLG919 and 3 nM PTX, and medium containing 0.1% DMSO is used as the vehicle treatment. PTX at 3 nM is a concentration with low inhibition rate (IR) of cell growth about 20%. At 0, 12, 24, 48, and 72 h after addition of drugs, cells are washed to remove dead cells and particles. Adherent cells are trypsinized and counted using a CountStar IC1000 Automated Cell Counter (Ruiyu-Biotech). Viability of the counted cells is confirmed by 0.1% trypan blue exclusion. The effect of NLG919 and PTX on the growth of cells is analyzed by plotting cell growth curves using viable cell numbers against time.
動物実験	動物モデル	C57BL/6 (H-2b, CD45.2) mice
	投薬量	200 mg/kg
	投与方法	Oral gavage

参考

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Bispecific prodrug nanoparticles circumventing multiple immune resistance mechanisms for promoting cancer immunotherapy [ Acta Pharm Sin B, 2022, 12(6):2695-2709]	PubMed: 35755274
Evaluation of Novel Inhibitors of Tryptophan Dioxygenases for Enzyme and Species Selectivity Using Engineered Tumour Cell Lines Expressing Either Murine or Human IDO1 or TDO2 [ Pharmaceuticals (Basel), 2022, 15(9)1090]	PubMed: 36145311
Parallel discovery of selective and dual inhibitors of tryptophan dioxygenases IDO1 and TDO2 with a newly-modified enzymatic assay [ Bioorg Med Chem, 2021, 39:116160]	PubMed: 33901770
Self-Delivery Photo-Immune Stimulators for Photodynamic Sensitized Tumor Immunotherapy [ ACS Nano, 2020, 10.1021/acsnano.0c06765]	PubMed: 33236625
Discovery of Novel Indoleamine 2,3-Dioxygenase 1 (IDO1) and Histone Deacetylase 1 (HDAC1) Dual Inhibitors Derived from the Natural Product Saprorthoquinone [ Molecules, 2020, 25(19)E4494]	PubMed: 33007982
Development of an In Vitro Assay to Assess Pharmacological Compounds and Reversion of Tumor-Derived Immunosuppression of Dendritic Cells [ Immunol Invest, 2020, 1-17]	PubMed: 32573300

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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