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. NLG919 is potent and selective inhibitor of IDO pathway with Ki value of 7nM and EC50 value of 75nM in a cell-based assays, with 15-20 fold more selectivity to IDO than TDO. Using human pDCsIDO1+ in allogeneic MLR reactions, NLG919 could block IDO-induced T cell suppression and restored robust T cell responses with EC50 value of 90nM, as well as with EC50 of 130nM in study using mouse pDCsIDO1+ from tumor-draining lymph nodes. Oral administration of NLG919 dissolved in the water at 3 mg/mL markedly enhanced the anti-tumor responses of naïve and reduced the tumor growth in mice bearing large established B16F10 tumors. An addition of subcutaneous administration at 1 mg/dose twice a day via injection plus 360 µg/day via an SC osmotic pump could enhance antitumor activity[1].
作用机制
The 4-phenylimidazole structure of NLG919 could inhibit IDO1 enzyme activity in noncompetitive manner and bound the heme iron at the IDO1-active site.[2]
IDO-IN-7 细胞实验
Cell Line
Concentration
Treated Time
Description
References
CTLL-2 cells
100 µM
24 hours
Increased IL-2 secretion by approximately 80%
Nat Commun. 2025 Jan 15;16(1):687.
PANC02 cells
750 ng/mL
5 hours
Evaluate the cellular uptake capability of PGEM carrier
Acta Biomater. 2020 Apr 1;106:289-300.
CT26 colorectal tumor cells
1 µM
24 hours
Evaluate cytotoxicity of HCNSP and HCNCP, results showed cell viability over 80%
Adv Sci (Weinh). 2020 Feb 25;7(8):1903332.
CT26 murine colorectal tumor cells
4.0 μg/mL
24 hours
Confirmed the inhibitory effect of NJ NPs on IFN-γ-induced IDO-1 activity, demonstrating a significant reduction in the Kyn/Trp ratio.
Acta Pharm Sin B. 2022 Jun;12(6):2695-2709.
4T1 murine breast tumor cells
10 µM
24 hours
Evaluated the photoactivity and ROS generation of PHPNJ NPs, showing significantly increased ROS production under acidic conditions (pH 6.5).
Acta Pharm Sin B. 2022 Jun;12(6):2695-2709.
MDA-MB-231 cells
100 µM
24 hours
Induced ICD, reduced proportion of Tregs among CD4+ T cells
Nat Commun. 2025 Jan 15;16(1):687.
4T1 cells
100 µM
24 hours
Induced immunogenic cell death (ICD), increased ATP release by 5.2-fold, HMGB1 release by 2.4-fold, and CRT surface exposure by ~30%
Nat Commun. 2025 Jan 15;16(1):687.
B16 tumor cells
50 µM
24 hours
Evaluate the cytotoxicity of NCSNPs on B16 tumor cells and their effect on inducing pyroptosis. Results showed that NCSNPs significantly induced pyroptosis and inhibited tumor cell proliferation.
Adv Sci (Weinh). 2024 May;11(20):e2305382.
Lymphocyte-HeLa cells co-culture system
20 µM
3 days
Assess whether BN@HM-OVA can reverse the inhibition of T cell proliferation caused by IDO. Results showed that BN@HM-OVA nanovaccine effectively stimulated T cell proliferation.
Bioact Mater. 2022 Mar 11;16:107-119.
CT26 colorectal tumor cells
1 µM
4 hours
Detect intracellular ROS generation, results showed significant increase in ROS upon laser irradiation
Adv Sci (Weinh). 2020 Feb 25;7(8):1903332.
HeLa cells
0–30 µM
48 hours
Evaluate the inhibitory effect of NLG-919 on IDO enzyme activity. Results showed that BN@HM-OVA nanovaccine inhibited IDO activity in a concentration-dependent manner.
Bioact Mater. 2022 Mar 11;16:107-119.
HeLa cells
50 nM–20 µM
48 hours
To evaluate the inhibitory effect of PEG2k-Fmoc-NLG on IDO activity, results showed that PEG2k-Fmoc-NLG(L) and PEG2k-Fmoc-NLG(S) could inhibit IDO activity, but were less active than free NLG919.
Nat Commun. 2016 Nov 7;7:13443.
HOS cells
10 µM
48 hours
Evaluate the anti-tumor activity of NP-Pt-IDOi on HOS cells, results showed NP-Pt-IDOi had the highest cytotoxicity and promoted apoptosis
Mater Today Bio. 2023 May 24;20:100675.
HeLa cells
50 nM –20 µM
48 hours
To test the IDO inhibitory activity of PSSN10, results showed PSSN10 blocked IDO function in a concentration-dependent manner.
Acta Pharmacol Sin. 2017 Jun;38(6):823-834.
Panc02 cells
25 μg/mL
6 hours
To evaluate intracellular H2S release and ROS production. Results showed that H2S levels and ROS signal intensity were significantly increased in SPNDNH group.
Adv Sci (Weinh). 2023 Dec;10(35):e2305150.
Human umbilical vein endothelial cells (HUVECs)
10–60 µM
Evaluate the toxicity of NCSNPs on normal cells. Results showed that NCSNPs had minimal impact on the viability of HUVECs, indicating their safety for normal cells.
Adv Sci (Weinh). 2024 May;11(20):e2305382.
IDO-IN-7 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Female Balb/C mice
4T1 mammary tumor model
Intraperitoneal injection
10 mg/kg
Once a day, started on day 12 and stopped on day 26 of experiments
The combination of NLG919 with PLG-CA4 and PI3Kγ inhibitor significantly suppressed the growth of breast cancer and improved the tumor suppression rate.
Adv Sci (Weinh). 2019 Apr 18;6(12):1900327
C57BL/6 mice
PANC02 pancreatic cancer model
Intravenous injection
10 mg/kg (NLG dosage)
Two injections at an interval of 2 days, followed by laser irradiation at 24 h after the second injection, and then three more injections at an interval of four days.
Evaluate the anti-tumor effect of N/PGEM/dp-16 NPs under laser irradiation. Results showed that N/PGEM/dp-16 NPs combined with laser irradiation significantly inhibited tumor growth, with negligible toxicity to liver and kidney.
Biomaterials. 2021 Feb;269:120629
C57 mice
Panc02 tumor-bearing model
Tail vein injection
16 mg/kg
Administered on the 1st, 4th, and 7th days
NLG919 improved the 5-FU-induced tumor immunosuppressive microenvironment by inhibiting the Kyn-AHR axis, enhancing the effect of chemoimmunotherapy.
J Nanobiotechnology. 2024 May 16;22(1):257
C57BL/6 mice
E.G7-OVA tumor model
Intratumoral injection
2 mg/kg per injection
Every 4 days for 3 times
Evaluate the antitumor efficacy of BN@HM-OVA nanovaccine in the E.G7-OVA tumor model. Results showed that BN@HM-OVA significantly inhibited tumor growth and prolonged survival in mice.
Bioact Mater. 2022 Mar 11;16:107-119.
C57BL/6 mice
B16F10 tumor model
Intratumoral injection
2.5 mg/kg
On Day 0, 3, and 6, total of three doses
Evaluate the antitumor efficacy of PPF NPs combined with irradiation, showing significant tumor suppression with complete tumor eradication in 30% of mice and successful rejection of a second tumor inoculation
J Nanobiotechnology. 2021 Jun 14;19(1):182
C57BL/6JGpt mice
KPC pancreatic cancer mouse model
Intravenous injection
2.8 mg/kg
Every 3 days until tumor volume reached 1500 mm³
Evaluate the antitumor efficacy of DNMCs in the KPC pancreatic cancer mouse model, results showed that DNMCs significantly inhibited tumor growth without substantial weight loss.
Mater Today Bio. 2025 Jan 13;31:101487
C57BL/6 mice
PANC02 pancreatic tumor model
Intravenous injection
20 mg/kg
Every five days for a total of 6 times
Evaluate the anti-tumor effect of PGEM carrier co-loaded with PTX and NLG919
Acta Biomater. 2020 Apr 1;106:289-300.
Mice
B16 tumor model
Intravenous injection
20 mg/kg NLG, 31.2 mg/kg SNAP
Every 2 days, duration not specified
Evaluate the antitumor efficacy of NCSNPs in the B16 tumor model. Results showed that NCSNPs significantly inhibited tumor growth and promoted immune responses.
Adv Sci (Weinh). 2024 May;11(20):e2305382.
C57BL/6 mice
Orthotopic pancreatic cancer model
Intravenous injection
200 μg/mL
Injection on day 0, 2, and 4; US irradiation on day 1, 3, and 5, repeated three times
To evaluate antitumor and anti-metastasis effects. Results showed that tumor growth was almost completely inhibited and metastasis was significantly restricted in SPNDNH+US group.
Adv Sci (Weinh). 2023 Dec;10(35):e2305150.
BALB/c mice
4T1.2 breast cancer model
Intravenous injection
25 mg/kg
Once every 3 days for 5 times
To evaluate the in vivo antitumor activity of PEG2k-Fmoc-NLG(L), results showed that PEG2k-Fmoc-NLG(L) significantly inhibited tumor growth and enhanced T-cell immune responses.
Nat Commun. 2016 Nov 7;7:13443.
Mice
Orthotopic osteosarcoma model
Intravenous injection
3.5 mg/kg Pt, 25 mg/kg NLG919
Three injections, lasting 20 days
Evaluate the anti-tumor activity of NP-Pt-IDOi in the orthotopic osteosarcoma mouse model, results showed NP-Pt-IDOi significantly inhibited tumor growth, activated the STING pathway, and remodeled the tumor microenvironment
Mater Today Bio. 2023 May 24;20:100675.
BALB/c mice
4T1 breast cancer model
Tail vein injection
4 mg/kg (Ce6 concentration) and 2.4 mg/kg (NLG919 concentration)
Every 3.5 days for a total of 4 cycles
Evaluate the therapeutic effect of NLG919@CF nanoparticles combined with anti-PD-1 antibody on breast cancer bone metastasis. Results showed that tumor volume and bone destruction were significantly reduced in the NLG919@CF + L + anti-PD-1 group.
J Nanobiotechnology. 2024 Sep 14;22(1):566
BALB/c mice
CT26 tumor-bearing mouse model
Intravenous injection
5 mg/kg
Every 5 days, total 2 times
Evaluate the antitumor effect of RIMNA in vivo, results showed that RIMNA combined with laser irradiation significantly inhibited the growth of primary and distant tumors and prolonged the survival time of mice.
J Nanobiotechnology. 2024 Sep 5;22(1):542
Balb/c mice
CT26 colorectal tumor model
Intravenous injection
5.0 mg/kg PPa and 2.6 mg/kg NLG919
Every 3 days for 3 times
Evaluate antitumor efficacy of HCNSP, results showed HCNSP+Laser significantly inhibited tumor growth and prolonged survival
Adv Sci (Weinh). 2020 Feb 25;7(8):1903332.
Female BALB/c mice
4T1 tumor model
In situ injection
5.7 mg/kg Abe and 31.8 mg/kg NLG919
Single dose, sustained for 7 days
Reduced tumor recurrence and pulmonary metastasis, prolonged survival, inhibited IDO-1 activity, increased CTL infiltration and activity
Nat Commun. 2025 Jan 15;16(1):687.
Mice
Orthotopic glioblastoma model
Oral
6 mg/mL
Continuously starting at day 7
IDO blockade synergized with chemo-radiation therapy to significantly prolong survival in mice bearing intracranial glioblastoma and triggered widespread complement deposition within tumors.
J Immunother Cancer. 2014 Jul 7;2:21
BALB/c female mice
Bilateral 4T1 tumor model
Intravenous injection
6 μmol/kg
Every two days for a total of three injections
Evaluate the inhibitory effect of PpIX-NLG@Lipo on primary and distant tumors in vivo
Theranostics. 2019 Jul 29;9(19):5542-5557
BALB/c mice
4T1 breast cancer model
Tail vein injection
6.5 mg/kg
Every 3 days, 3 times in total
To evaluate the anti-tumor effect of NLG919@Lip-pep1, results showed a tumor growth inhibition rate of 73% and significantly reduced lung metastatic nodules
Acta Pharm Sin B. 2023 May;13(5):2176-2187
Balb/c mice
Subcutaneous CT26 colon tumor model and orthotopic 4T1 breast tumor model
Intravenous injection
DOX 5 mg/kg, aNLG919 25 mg/kg
Injections at day 0, 3, and 6
To evaluate the antitumor efficacy of DNCaNPs, showing significant tumor growth suppression and extended survival
Nanomicro Lett. 2020 Nov 22;13(1):29.
BALB/c mice
4T1 breast tumor model and CT26 colorectal tumor model
Intravenous injection
NLG919 10 mg/kg, JQ1 15 mg/kg
Every 3 days for 5 doses
Assessed the antitumor efficacy and immunomodulatory effects of PHPNJ NPs, showing significant tumor growth inhibition, prolonged survival, enhanced CD8? T cell infiltration, and reduced Tregs.
Acta Pharm Sin B. 2022 Jun;12(6):2695-2709.
BALB/c mice
4T1 breast cancer model
Intravenous injection
NLG919 5 mg/kg, MSA-2 2.4 mg/kg
Every 2 days for a total of 3 times
Evaluated antitumor efficacy of MN NPs, showing significant tumor growth inhibition and immune activation
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