Indoleamine 2,3-Dioxygenase (IDO) Inhibitor

Necrostatin-1 (Nec-1) is a potent and cross the blood-brain barrier necroptosis inhibitor with an EC₅₀ of 490 nM in Jurkat cells. Necrostatin-1 inhibits RIP1 kinase (EC₅₀=182 nM). Necrostatin-1 is also an IDO inhibitor.

Epacadostat (INCB 024360) is a potent and selective indoleamine 2,3-dioxigenase 1 (IDO1) inhibitor with an IC₅₀ of 71.8 nM. Epacadostat can effectively reduce Trp metabolism, entailing increased activation and maturation of dendritic cells, and enhanced proliferation of effector T cells and natural killer cells (NKs), as well as attenuated Tregs expansion.

3-TYP is an inhibitor of SIRT3 (IC₅₀of 38 μM) and an inhibitor of Methionine Adenosyltransferase (MAT) 2 and Indoleamine 2,3-Dioxygenase (IDO). There may be many off-target sites for 3-TYP that need to be examined, such as NAD-dependent enzymes, including dehydrogenases.

Indoximod (1-Methyl-D-tryptophan) is an orally active indoleamine 2,3-dioxygenase (IDO) pathway inhibitor. Indoximod acts as a Trp mimetic in regulating mTOR. Indoximod is an immunometabolic adjuvant used for the research of cancer.

Brassinin is an indole derivative found in cruciferous plants. Brassinin acts as an IDO inhibitor (K_i = 97.7 μM). Brassinin inhibits angiogenesis and induces apoptosis, autophagy, paraptosis, ROS production, and ER stress. Brassinin selectively stimulates lysosomal degradation of Tie2 and promotes lysosomal and proteasomal degradation of FGFR1 in endothelial cells, downregulating AKT and ERK phosphorylation. Brassinin inhibits endothelial cell proliferation, migration, tube formation, spheroid sprouting, and angiogenesis. Brassinin inhibits PI3K/Akt/mTOR/S6K1 signaling, upregulates p21 and p27, and induces G1 phase cell cycle arrest through RB hypophosphorylation. Brassinin inhibits tyrosinase catalytic activity, reduces tyrosinase mRNA, and inhibits MITF nuclear translocation. Brassinin is used for research on triple-negative breast cancer, chronic myeloid leukemia, colon cancer, glioma, atherosclerosis, and skin cancer.

Palmatine chloride is an orally active and irreversible indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor with IC₅₀s of 3 μM and 157μM against HEK 293-hIDO-1 and rhIDO-1, respectively. Palmatine chloride can also inhibit West Nile virus (WNV) NS2B-NS3 protease in an uncompetitive manner with an IC₅₀ of 96 μM. Palmatine chloride shows anti-cancer, anti-oxidation, anti-inflammatory, neuroprotection, antibacterial, anti-viral activities.

Linrodostat (BMS-986205) is a selective and irreversible indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor with an IC₅₀ value of 1.1 nM in IDO1-HEK293 cells. Linrodostat is well tolerated with potent pharmacodynamic activity in advanced cancers.

PF-06840003 (EOS200271) is a highly selective, orally active and brain-penetrant IDO-1 inhibitor with IC₅₀s of 0.41 μM, 0.59 μM, and 1.5 μM for hIDO-1, dIDO-1, and mIDO-1, respectively.

Coptisine chloride is an alkaloid from Chinese goldthread, and acts as an efficient uncompetitive IDO inhibitor with a K_i value of 5.8 μM and an IC₅₀ value of 6.3 μM. Coptisine chloride is a potent H1N1 neuraminidase (NA-1) inhibitor with an IC₅₀ of 104.6?μg/mL and can be used for influenza A (H1N1) infection.

(S)-Indoximod (1-Methyl-L-tryptophan) is an inhibitor of indoleamine 2,3-dioxygenase (IDO) (K_i: 19 μM). (S)-Indoximod can be used for the research of cancer and neurological disease.

LM10 is a potent inhibitor of tryptophan 2,3-dioxygenase (TDO). Tryptophan 2,3-dioxygenase (TDO) is an unrelated hepatic enzyme that also degrades tryptophan along the kynurenine pathway. LM10 has the potential for the research of cancer diseases.

IDO-IN-7 (NLG-919 analogue) is a a potent IDO1 inhibitor with an IC₅₀ of 38 nM.

IDO1/TDO-IN-4 is a potent IDO1/TDO dual inhibitor, with IC₅₀ values of 3.53 μM (IDO1) and 1.15 μM (TDO). IDO1/TDO-IN-4 forms hydrogen bond with IDO1, and π−π stacking interaction with TDO. IDO1/TDO-IN-4 can be used in the research of depression, and depression-induced infectious, metabolic, and autoimmune disorders.

(Rac)-Indoximod (1-Methyl-DL-tryptophan) is an indoleamine 2,3-dioxygenase (IDO) inhibitor. Co-treatment with IFN-γ and (Rac)-Indoximod markedly reduces the activity of human cardiac myofibroblasts (hCMs) expressing α-SMA and induces apoptosis through up-regulating the IRF-1, Fas, and FasL genes.

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

LY-3381916 (IDO1-IN-5) is a potent, selective and brain penetrated inhibitor of IDO1 activity, binds to apo-IDO1 lacking heme rather than mature heme-bound IDO1.

Palmatine hydroxide is an orally active and irreversible indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor with IC₅₀s of 3 μM and 157μM against HEK 293-hIDO-1 and rhIDO-1, respectively. Palmatine hydroxide can also inhibit West Nile virus (WNV) NS2B-NS3 protease in an uncompetitive manner with an IC₅₀ of 96 μM. Palmatine hydroxide shows anti-cancer, anti-oxidation, anti-inflammatory, neuroprotection, antibacterial, anti-viral activities.

Regaloside B is a phenylpropane. Regaloside B can be isolated from Lilium longiflorum. Regaloside B can inhibit the expression of VCAM-1, iNOS, and COX-2, with a p-p65/p-65 ratio. Regaloside B inhibits the mRNA of various chemokines and angiogenic factors (CXCL9, CXCL10, IL8, IDO). Regaloside B has anti-inflammatory activity. Regaloside B can be used for osteogenic differentiation research.

DP00477 is a potent IDO1 (indoleamine 2,3-dioxygenase 1) inhibitor with an IC₅₀ value of 7.0 µM. DP00477 has the potential for the research of cancer.

IDO1-IN-18 (Compound 14) is a potent inhibitor of IDO1. IDO1-IN-18 has the potential for the research of cancer diseases.