生物活性

• 描述IDO1 (Indoleamine 2,3-dioxygenase-1) is a heme-containing monomeric oxidoreductase, which can catalyze the degradation of the essential amino acid tryptophan to N-formyl-kynurenine, an intermediate metabolized through a series of steps to form NAD⁺. IDO1 is considered to play an important role in the induction of tumor immune tolerance, which can regulate the immunosuppressive mechanisms responsible for tumor escape from host immune surveillance. Indoximod is the D-isomer of 1-methyl-tryptophan which is the first IDO inhibitor with Ki value of 7-70μM^[1]. The two stereoisomers, 1-methyl-D-Trp (Indoximod) and 1-methyl-L-Trp, possess potentially different biological properties. Compared with 1-methyl-L-Trp, Indoximod exhibited much less potency to IDO enzymic activity on kynurenine production in both purified enzyme and in HeLa cell–based (IC25>100μM) assays. However, Indoximod showed much significant effect on reversing the suppression of T cells created by DCs^IDO1+ (dendritic cells^IDO1+), which suggesting that Indoximod may function more efficiently against immunosuppression. Consistent with this, an in vivo study showed that Indoximod (400 mg/kg by oral gavage twice daily, five times a week) was more efficacious as an anticancer agent dependent on IDO gene expression in mouse models of transplantable melanoma and transplantable and autochthonous breast cancer, with combined treatment with chemo-immunotherapy regimens using cyclophosphamide, paclitaxel, or gemcitabine^[2].
• 作用机制Indoximod is an analogue of D-Trp, which works as a competitive inhibitor for indoleamine 2,3-dioxygenase.^[1]

• 动物研究
  剂量	Mice: 400 mg/kg[2] (p.o.), 70 mg/kg (i.p.)
  给药途径	p.o., i.p.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02913430	Metastatic Breast Cancer	Phase 2	Recruiting	March 2020	United States, Pennsylvania ... more >> Magee-Womens Hospital UPMC Recruiting Pittsburgh, Pennsylvania, United States, 15213 Contact: Shannon L. Cieply    412-641-2357 Collapse <<
  NCT02052648	Glioblastoma Multiforme ... more >> Glioma Gliosarcoma Malignant Brain Tumor Collapse <<	Phase 1 Phase 2	Active, not recruiting	October 2018	United States, California ... more >> Eden Medical Center Castro Valley, California, United States, 94546 Cedars-Sinai Medical Center Los Angeles, California, United States, 90048 UC Irvine Chao Family Comprehensive Cancer Center Orange, California, United States, 92868 United States, Florida Moffitt Cancer Center Tampa, Florida, United States, 33612 United States, Georgia University Cancer and Blood Center Athens, Georgia, United States, 30607 Children's Healthcare of Atlanta Atlanta, Georgia, United States, 30342 Georgia Regents University Augusta, Georgia, United States, 30912 United States, Illinois University of Chicago Chicago, Illinois, United States, 60637 United States, Iowa University of Iowa Hospitals and Clinics Iowa City, Iowa, United States, 52242 United States, Kentucky University of Kentucy Lexington, Kentucky, United States, 40536 United States, Minnesota John Nasseff Neuroscience Institute Minneapolis, Minnesota, United States, 55407 United States, New Mexico University of New Mexico Comprehensive Cancer Center Albuquerque, New Mexico, United States, 87131 United States, North Carolina Wake Forest Baptist Health Comprehensive Cancer Center Winston-Salem, North Carolina, United States, 27157 United States, Pennsylvania Penn State Hershey Medical Center Hershey, Pennsylvania, United States, 17033 United States, Texas Texas Oncology Austin, Texas, United States, 78705 United States, Utah Huntsman Cancer Center Salt Lake City, Utah, United States, 84112 United States, Virginia Virginia Cancer Specialists Fairfax, Virginia, United States, 22031 Collapse <<
  NCT03165318	Muscle Loss Post Anterior Cruc... more >>iate Ligament Reconstruction Collapse <<	Not Applicable	Enrolling by invitation	July 2018	Singapore ... more >> National University Health System Singapore, Singapore, 119074 Collapse <<

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