Cell lines

Treg cells

Preparation method

The solubility of this compound in DMSO is limited. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 ℃ for several months.

Reacting condition

0.05 mM

Applications

Indoximod significantly inhibited the differentiation of Treg cells, especially that of IL-10+ Treg cells, whilst showed no effect on TGF-β1+ Treg cells. Treg cells co-cultured with Indoximod-pretreated ESCs exhibited less suppressive function. The results indicated that indoleamine 2,3-dioxygenase-1 (IDO1) was involved in the differentiation and suppressive function of Treg cells in endometriosis.

Animal models

Mice bearing 4T1 tumors

Dosage form

400 mg/kg; p.o.; b.i.d., 5 times a week

Applications

In mice bearing 4T1 tumors, DL-Indoximod in combination with Cyclophosphamide enhanced antitumor immunity. In addition, the drug combination induced a marked decrease in tumor size. Compared with the combination of L-Indoximod and Cyclophosphamide, D-Indoximod combined with Cyclophosphamide significantly prolonged the survival period.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Indoximod is an Indoleamine 2,3-dioxygenase (IDO) pathway inhibitor. IDO is a tryptophan-catabolizing enzyme that tumors use to create a state of immunosuppression. [1]
The immunosuppressive activity of IDO leads to an increase in the number of T-regulatory cells, as measured by their Foxp3+/CD4+/CD25+ phenotype. Indoximod has also been shown to reduce the number of T-regulatory cells [2]. In MMTV-Neu mice, researchers looked at the activity of indoximod with and without paclitaxel [3]. The combination of docetaxel and indoximod is more toxic than docetaxel monotherapy.  A single 1200 mg dose of indoximod almost totally saturates the gut, and higher doses do not significantly increase peak serum levels. The single-agent phase I trial of indoximod demonstrated very good oral bioavailability and a mild toxicity profile with no significant myelosuppression, and no maximally tolerated dose was identified up to 2000 mg orally twice daily [1].
Blockade of IDO with indoximod enhanced the adoptive immunologic response to antigens and dendritic cell (DC) vaccines in LLC mouse models.
References:
[1]. Soliman HH, Jackson E, Neuger T et al. A first in man phase I trial of the oral immunomodulator, indoximod, combined with docetaxel in patients with metastatic solid tumors. Oncotarget. 2014 Sep 30;5 (18):8136-46.
[2]. Munn DH. Blocking IDO activity to enhance anti-tumor immunity. Front Biosci (Elite Ed). 2012 Jan 1;4:734-45.
[3]. Muller AJ, DuHadaway JB, Donover PS et al.Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat Med. 2005 Mar;11(3):312-9. Epub 2005 Feb 13.