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.

IDO1/TDO-IN-15 is a dual IDO1/TDO inhibitor with an IDO1 IC₅₀ of 0.19 μM and a TDO IC₅₀ of 0.37 μM. IDO1/TDO-IN-15 is applicable to the research of cancer and Alzheimer's disease.

IDO1/TDO-IN-18 is a IDO1/TDO inhibitor with an IC₅₀ of 26.54 μM against human IDO1 and an IC₅₀ of 15.63 μM against human TDO. IDO1/TDO-IN-18 targets the apo-forms of IDO1 and TDO to displace the heme cofactor, attenuates the IDO1/SHP-2 interaction, reduces the output of the kynurenine pathway in tumor cells, and inhibits the proliferation and migration of cancer cells. IDO1/TDO-IN-18 can serve as a chemical probe for enzymology and signal transduction-related studies of the IDO1/TDO axis, and can also be used in cancer-related research.

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.

PROTAC IDO1 Degrader-1 is the first potent IDO1 (indoleamine 2,3-dioxygenase 1) degrader that hijacks IDO1 to Cereblon E3 ligase to introduce IDO1 into UPS and eventually achieve ubiquitination and degradation (DC₅₀=2.84 μM). PROTAC IDO1 Degrader-1 moderately improves the tumor-killing activity of H ER2 CAR-T cells.

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.