NLG919 Chemical Properties

Melting point:

143 - 146°C

Boiling point:

524.6±33.0 °C(Predicted)

Density 

1.27±0.1 g/cm3(Predicted)

storage temp. 

-20°C

solubility 

Soluble in DMSO (up to 15 mg/ml)

pka

14.85±0.20(Predicted)

form 

solid

color 

White

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.

InChI

InChI=1S/C18H22N2O/c21-18(13-6-2-1-3-7-13)10-16-14-8-4-5-9-15(14)17-11-19-12-20(16)17/h4-5,8-9,11-13,16,18,21H,1-3,6-7,10H2

InChIKey

YTRRAUACYORZLX-UHFFFAOYSA-N

SMILES

C(O)(C1CCCCC1)CC1C2=C(C=CC=C2)C2=CN=CN21

NLG919 Usage And Synthesis

Description

(±)-NLG-919 is an indoleamine 2,3-dioxygenase (IDO) pathway inhibitor (K_i = 7 nM; EC₅₀ = 75 nM). (±)-NLG-919 inhibits IDO-induced T cell suppression and restores T cell response during allogenic mixed lymphocyte reactions in vitro (ED₅₀s = 80 and 120 nM, respectively). In vivo, (±)-NLG-919 induces a 95% reduction in tumor volume when administered in conjunction with a pmel-1 T cell vaccine. Formulations containing (±)-NLG-919 are under investigation in clinical trials for treatment of glioblastoma, melanoma, pancreatic, and breast cancers.

Uses

NLG919 is a potent indoleamine-2,3-dioxygenase (IDO) pathway inhibitor and is suitable for the treatment of immunosuppression associated with cancer.

Synthesis

Sodium borohydride (81 mg, 2.14 mmol) was slowly added to a methanol solution (5 mL) containing 1-cyclohexyl-2-[5H-imidazo[4,3-a]isoindol-5-yl]ethan-1-one (300 mg, 1.07 mmol) at 0 °C. The reaction mixture was stirred continuously at 0 °C for 30 min. Subsequently, the reaction was quenched with deionized water (30 mL) and extracted with ethyl acetate (50 mL x 2). The organic phases were combined, washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was removed by concentration under reduced pressure and the residue was purified by fast column chromatography using a solvent mixture of dichloromethane and methanol (1% to 6% gradient) as eluent to afford 1-cyclohexyl-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethanol as a colorless oil (250 mg, 83% yield). Mass spectrometry result: m/z = 283.1 [M + H]+.

target

IDO pathway

References

[1] M. MAUTINO. Abstract 491: NLG919, a novel indoleamine-2,3-dioxygenase (IDO)-pathway inhibitor drug candidate for cancer therapy.[J]. Cancer research, 2013, 73 1: 491-491. DOI:10.1158/1538-7445.am2013-491
[2] MINGHUI LI. The indoleamine 2,3-dioxygenase pathway controls complement-dependent enhancement of chemo-radiation therapy against murine glioblastoma.[J]. Journal for Immunotherapy of Cancer, 2014, 2: 21. DOI:10.1186/2051-1426-2-21
[3] XIANGJING MENG. Combinatorial antitumor effects of indoleamine 2,3-dioxygenase inhibitor NLG919 and paclitaxel in a murine B16-F10 melanoma model.[J]. International Journal of Immunopathology and Pharmacology, 2017, 30 3: 215-226. DOI:10.1177/0394632017714696

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