GDC-0919; NLG-919; RG-6078

MF C18H22N2O
MW: 282.17321
GDC-0919; NLG-919; RG-6078, GDC0919; GDC-0919; GDC 0919; NLG919; NLG 919; NLG-919; RG6078; RG-6078; RG 6078.

 1-cyclohexyl-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethanol
CAS No.1402836-58-1

GDC-0919, also known as NLG919 and RG6078, is an orally available inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), with potential immunomodulating and antineoplastic activities. Upon administration, 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 dendritic cells (DCs), natural killer (NK) cells, T-lymphocytes, and causes a reduction in tumor-associated regulatory T-cells (Tregs). Activation of the immune system, which is suppressed in many cancers, may induce a cytotoxic T-lymphocyte (CTL) response against the IDO1-expressing tumor cells

• Originator Lankenau Institute for Medical Research
• Developer Genentech; NewLink Genetics Corporation
• Class Antineoplastics; Small molecules
• Mechanism of Action Immunomodulators; Indoleamine-pyrrole 2,3-dioxygenase inhibitors

Phase I Solid tumours

Patent ID	Date	Patent Title
US2015210769	2015-07-30	ANTIBODY MOLECULES TO PD-1 AND USES THEREOF
US2014066625	2014-03-06	Fused Imidazole Derivatives Useful as IDO Inhibitors

• 27 Sep 2015 Pharmacokinetics results from a phase-I clinical trial in Solid tumours presented at the European Cancer Congress 2015 (ECC-2015)
• 27 Sep 2015 Positive efficacy and safety results from a phase-I clinical trial in Solid tumours presented at the European Cancer Congress 2015 (ECC-2015)
• 31 Jul 2015 Phase-I clinical trials in Solid tumours (Combination therapy, Late-stage disease, Second-line therapy or greater) in USA (PO) (NCT02471846)

PATENT
http://www.google.com/patents/WO2012142237A1?cl=en

PATENT

US-20160002249-A1 / 2016-01-07

Fused Imidazole Derivatives Useful as IDO Inhibitors

13041-cyclohexyl-2-(5H-imidazo[5,1- a]isoindol-5-yl)ethanol79 ¹H NMR (a mixture of diastereomers) 1.10-1.37 (m, 6H), 1.66-1.80 (m, 5H), 2.05 (m, 2H), 2.15 (m, 1H), 3.72 (m, 1H), 5.36 and 5.46 (two m, 1H), 7.16 (s, 1H), 7.25 (m, 1H), 7.34 (m, 1H), 7.43 (d, 1H, J = 7.6 Hz), 7.54 (d, 1H, J = 7.6 Hz), 7.80 (s, 1H)

WO2011056652A1 *	Oct 27, 2010	May 12, 2011	Newlink Genetics	Imidazole derivatives as ido inhibitors
WO2012142237A1 *	Apr 12, 2012	Oct 18, 2012	Newlink Geneticks Corporation	Fused imidazole derivatives useful as ido inhibitors
WO2014159248A1	Mar 10, 2014	Oct 2, 2014	Newlink Genetics Corporation	Tricyclic compounds as inhibitors of immunosuppression mediated by tryptophan metabolization
US8722720	Oct 27, 2010	May 13, 2014	Newlink Genetics Corporation	Imidazole derivatives as IDO inhibitors
US9260434	Oct 14, 2013	Feb 16, 2016	Newlink Genetics Corporation	Fused imidazole derivatives useful as IDO inhibitors
US20140066625 *	Oct 14, 2013	Mar 6, 2014	Newlink Genetics Corporation	Fused Imidazole Derivatives Useful as IDO Inhibitors
US20160002249 *	Jul 8, 2015	Jan 7, 2016	Newlink Genetics Corporation	Fused Imidazole Derivatives Useful as IDO Inhibitors

REFERENCES
Nature Reviews Drug Discovery14,373(2015)doi:10.1038/nrd4658
http://www.ncbi.nlm.nih.gov/pubmed/21517759
http://www.roche.com/irp150128-annex.pdf
/////CRD1152, CRD 1152, CRD-1152, Curadev,  Research Collaboration, Licensing Agreement, Develop,  Cancer Immunotherapeutic, IDO1 and TDO inhibitors

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