product name NLG919
Description: NLG919 also known as RG6078 and GDC-0919, is a potent and orally available IDO (indoleamine-(2,3)-dioxygenase) pathway inhibitor with Ki/EC50 of 7 nM/75 nM in cell-free assays. NLG919 targets and binds to IDO1, a cytosolic enzyme responsible for the oxidation of the essential amino acid tryptophan into kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, this agent increases tryptophan levels, restores the proliferation and activation of various immune cells, including NK cells, T-lymphocytes, and causes a reduction in tumor-associated regulatory T-cells.
References: J Immunother Cancer. 2014 Jul 7;2:21; AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 491.
282.38
Formula
C18H22N2O
CAS No.
1402836-58-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 15 mg/mL warmed (53.1 mM)
Water: <1 mg/mL
Ethanol: 30 mg/mL (106.2 mM)
Solubility (In vivo)
Synonyms
RG6078， GDC-0919
other peoduct :
| In Vitro |
In vitro activity: 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. Kinase Assay: Cell Assay: NLG919 potently blockes IDO-induced T cell suppression and restores robust T cell responses with an EC50=90 nM. NLG919 also abrogates IDO-induced suppression of antigen-specific T cells (OT-I or pmel-1) in vitro, (ED50=130 nM ) using mouse IDO+ pDCs from tumor-draining lymph nodes. |
|---|---|
| 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. |
| Animal model | Mice bearing large established B16F10 tumor |
| Formulation & Dosage | Dissolved in water at 3 mg/mL; 6 mg/day injected via IP, or administered subcutaneously at 1 mg/dose twice a day via injection plus 360 μg/day via an SC osmotic pump. |
| References | J Immunother Cancer. 2014 Jul 7;2:21; AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 491. |
