ido/tdo in 1

IDO1/TDO-IN-6 (compound 11) is a dual inhibitor targeting IDO1 and TDO, exhibiting IC50 values of 2.25 μM for IDO1 and 2.89 μM for TDO. The compound further demonstrates Ki values of 1.9 μM for IDO1 and 3.1 μM for TDO, marking its potential utility in cancer and immunology research [1].

(R)-IDO/TDO-IN-1 (compound 25), an indoleamine-2,3-dioxygenase (IDO) inhibitor, demonstrates good pharmacokinetic properties and exerts anti-tumor effects in the MC38 xenograft model. This compound exhibits synergy when combined with the anti-PD-1 monoclonal antibody (SHR-1210) [1].

IDO/TDO-IN-1 is an orally active dual indoleamine-2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) inhibitor (IC50s: 9.7 and 47 nM).

IDO1/TDO-IN-4 displays potent inhibition of both IDO1 (IC50 = 3.53 μM) and TDO (IC50 = 1.15 μM) and has an acceptable safety profile and pharmacokinetic properties. IDO1/TDO-IN-4 forms a hydrogen bond with IDO1, and π π stacking interaction with TDO. IDO1/TDO-IN-4 can be used in the research of depression and inflammation-induced depression [1].

IDO1/TDO-IN-3 is a powerful inhibitor targeting IDO1 and TDO enzymes. It displays noteworthy effectiveness against IDO1 (IC50: 0.005 μM) and TDO (IC50: 0.004 μM). Additionally, IDO1/TDO-IN-3 demonstrates considerable in vivo anti-tumor properties while exhibiting no apparent toxicity [1].

IDO1/TDO-IN-2 (Compound 1) is a potent IDO1/TDO dual inhibitor with IC50s of 0.1 and 0.07 μM, respectively. IDO1/TDO-IN-2 has the potential for cancer research[1].

IDO1/TDO-IN-1 (30) is a highly effective inhibitor that targets both IDO1 and TDO enzymes with uncompetitive (Ki = 0.23 μM) and competitive (Ki = 0.73 μM) mechanisms, respectively. This compound, IDO1/TDO-IN-1 (30), exhibits a significant capacity to induce cell apoptosis via the potential mitochondria-mediated Bcl-2/Bax pathway [1].

KYN-101 is a potent, selective synthetic antagonist of aryl hydrocarbon receptor (AHR) with IC50 of 22 nM in human HepG2 DRE-luciferase reporter assay and 23 nM in murine Hepa1 Cyp-luc assay.KYN-101 reverses IDO/TDO-mediated tumor progression and improves the efficacy of PD-1 blockade in B16 IDO tumor-bearing mice, as well as CT26 colorectal cancer model expressing endogenous high levels of IDO.

IDO/Tubulin-IN-2 (HT2) is a powerful inhibitor of both TDO and tubulin. This compound demonstrates significant efficacy against various cancer cell lines, including U87, HepG2, A549, HCT-116, and LO2, with respective IC50 values of 0.43, 0.036, 0.041, 0.095, and 1.04 μM. Additionally, IDO/Tubulin-IN-2 markedly enhances antitumor activity [1].