Purity: > 98%
|Product-Name:||IDO Pathway inhibitor|
Indoximod(cas# 110117-83-4) is an IDO pathway inhibitor, and reverses IDO-mediated immune suppression.
The overexpression of IDO in tumors and tumor-draining lymph nodes induces immune tolerance and enhances tumor growth in vivo. 1-methyl-D-Tryptophan is an inhibitor of IDO (IC50 = 7 μM) that is effective in vivo.
1. Oncotarget. 2016 Apr 19;7(16):22928-38. doi: 10.18632/oncotarget.8216.
A phase I study of indoximod in patients with advanced malignancies.
Soliman HH(1), Minton SE(1), Han HS(1), Ismail-Khan R(1), Neuger A(1), Khambati
F(1), Noyes D(1), Lush R(1), Chiappori AA(1), Roberts JD(2), Link C(3), Vahanian
NN(3), Mautino M(3), Streicher H(4), Sullivan DM(1), Antonia SJ(1).
(1)H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
(2)Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia,
(3)NewLink Genetics Inc., Ames, Iowa, USA.
(4)Cancer Therapeutics Evaluation Program, National Cancer Institute, Bethesda,
PURPOSE: Indoximod is an oral inhibitor of the indoleamine 2,3-dioxygenase
pathway, which causes tumor-mediated immunosuppression. Primary endpoints were
maximum tolerated dose (MTD) and toxicity for indoximod in patients with advanced
solid tumors. Secondary endpoints included response rates, pharmacokinetics, and
EXPERIMENTAL DESIGN: Our 3+3 phase I trial comprised 10 dose levels (200, 300,
400, 600, and 800 mg once/day; 600, 800, 1200, 1600, and 2000 mg twice/day).
Inclusion criteria were measurable metastatic solid malignancy, age ≥18 years,
and adequate organ/marrow function. Exclusion criteria were chemotherapy ≤ 3
weeks prior, untreated brain metastases, autoimmune disease, or malabsorption.
RESULTS: In 48 patients, MTD was not reached at 2000 mg twice/day. At 200 mg
once/day, 3 patients previously treated with checkpoint inhibitors developed
hypophysitis. Five patients showed stable disease >6 months. Indoximod plasma AUC
and Cmax plateaued above 1200mg. Cmax (~12 μM at 2000 mg twice/day) occurred at
2.9 hours, and half-life was 10.5 hours. C reactive protein (CRP) levels
increased across multiple dose levels.
CONCLUSIONS: Indoximod was safe at doses up to 2000 mg orally twice/day. Best
response was stable disease >6 months in 5 patients. Induction of hypophysitis,
increased tumor antigen autoantibodies and CRP levels were observed.
2. Oncotarget. 2014 Sep 30;5(18):8136-46.
A first in man phase I trial of the oral immunomodulator, indoximod, combined
with docetaxel in patients with metastatic solid tumors.
Soliman HH(1), Jackson E(2), Neuger T(1), Dees EC(3), Harvey RD(4), Han H(1),
Ismail-Khan R(1), Minton S(1), Vahanian NN(5), Link C(5), Sullivan DM(1), Antonia
(1)H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
(2)University of South Florida, Tampa, FL.
(3)University of North Carolina/Lineberger Cancer Center, Chapel Hill, NC.
(4)Winship Cancer Institute of Emory University, Atlanta, GA.
(5)NewLink Genetics Inc, Ames, IA.
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is an enzyme that tumors use to
create a state of immunosuppression. Indoximod is an IDO pathway inhibitor.
Preclinical studies demonstrated that indoximod combined with chemotherapy was
synergistic in a mouse model of breast cancer. A phase I 3+3 trial was designed
to study the combination of docetaxel and indoximod.
METHODS: Docetaxel was administered at 60 mg/m2 intravenously every 3 weeks dose
levels 1-4 and 75 mg/m2 for dose level 5. Indoximod was given at 300, 600, 1000,
2000, and 1200 mg PO twice daily continuously for levels 1-5, respectively. Serum
drug levels were measured.
RESULTS: Twenty-seven patients were treated, with 22 evaluable for response. DLTs
included grade 3 dehydration (level 1), hypotension(level 4), mucositis (level 4)
and grade 5 enterocolitis (level 2). Dose level 5 is the recommended phase II
dose. The most frequent adverse events were fatigue (58.6%), anemia (51.7%),
hyperglycemia (48.3%), infection (44.8%), and nausea (41.4%). There were 4
partial responses (2 breast, 1 NSCLC, 1 thymic tumor). No drug-drug interactions
CONCLUSIONS: Docetaxel plus indoximod was well tolerated with no increase in
expected toxicities or pharmacokinetic interactions. It was active in a
pretreated population of patients with metastatic solid tumors.