Navoximod | IDO-IN-7 | CAS#1402837-78-8 | IDO Inhibitor

MedKoo Cat#: 327017 | Name: Navoximod free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Navoximod, also known as IDO-IN-7 and NLG-1488, is an indoleamine 2,3-dioxygenase (IDO) inhibitor. It is also used as an immunomodulator and an antineoplastic.

Chemical Structure

Navoximod free base

CAS#1402837-78-8 (free base)

Theoretical Analysis

MedKoo Cat#: 327017

Name: Navoximod free base

CAS#: 1402837-78-8 (free base)

Chemical Formula: C18H21FN2O2

Exact Mass: 316.1587

Molecular Weight: 316.38

Elemental Analysis: C, 68.34; H, 6.69; F, 6.01; N, 8.85; O, 10.11

Price and Availability

Size	Price	Availability
50mg	USD 550.00	2 Weeks
100mg	USD 950.00	2 Weeks
200mg	USD 1,650.00	2 Weeks
500mg	USD 2,650.00	2 Weeks

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Related CAS #

1793075-63-4 (phosphate) 1402837-78-8 (free base)

Synonym

Navoximod; IDO-IN-7; IDOIN7; IDO IN 7; Navoximod Phosphate; NLG-1488; NLG 1488; NLG1488.

IUPAC/Chemical Name

(1R,4r)-4-((R)-2-((S)-6-fluoro-5H-imidazo[5,1-a]isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol

InChi Key

YGACXVRLDHEXKY-WXRXAMBDSA-N

InChi Code

InChI=1S/C18H21FN2O2/c19-14-3-1-2-13-16-9-20-10-21(16)15(18(13)14)8-17(23)11-4-6-12(22)7-5-11/h1-3,9-12,15,17,22-23H,4-8H2/t11-,12-,15-,17+/m0/s1

SMILES Code

O[C@@H]([C@H]1CC[C@H](O)CC1)C[C@@H](C2=C3C=CC=C2F)N4C3=CN=C4

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Related CAS# 1402837-78-8 (Navoximod free base); 1793075-63-4 (Navoximod phosphate)

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Navoximod (GDC-0919; NLG-919) is a potent IDO (indoleamine-(2,3)-dioxygenase) pathway inhibitor with Ki/EC50 of 7 nM/75 nM.

In vitro activity:

As an initial investigation, this study evaluated levels of kynurenine following graded concentrations of GDC-0919 in this study’s human glioblastoma cell lines in vitro. GDC-0919 demonstrated potent inhibition of kynurenine production, with median effective dose (ED50) concentrations ranging from 7 nM - 1.77 μM and near complete inhibition at 5 μM (Fig. 3A). Reference: Clin Cancer Res. 2018 Aug 1;24(15):3632-3643. https://pubmed.ncbi.nlm.nih.gov/29691296/

In vivo activity:

In B16-F10 tumor-bearing mice, NLG919 was uniformly distributed throughout tumors and decreased kynurenine levels and kynurenine/tryptophan ratios in tumors and plasma for 6-12 h. NLG919 suppressed tumor growth in a dose-dependent manner and exhibited maximum efficacy at 100 mg/kg. Reference: Int J Immunopathol Pharmacol. 2017 Sep;30(3):215-226. https://pubmed.ncbi.nlm.nih.gov/28604143/

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	316.09
	Ethanol	63.0	199.13

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 316.38 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Chen Y, Xiong T, Zhao X, Du J, Sun W, Fan J, Peng X. Tumor Cell-Responsive Photodynamic Immunoagent for Immunogenicity-Enhanced Orthotopic and Remote Tumor Therapy. Adv Healthc Mater. 2023 Feb;12(5):e2202085. doi: 10.1002/adhm.202202085. Epub 2022 Nov 27. PMID: 36377488. 2. Kesarwani P, Prabhu A, Kant S, Kumar P, Graham SF, Buelow KL, Wilson GD, Miller CR, Chinnaiyan P. Tryptophan Metabolism Contributes to Radiation-Induced Immune Checkpoint Reactivation in Glioblastoma. Clin Cancer Res. 2018 Aug 1;24(15):3632-3643. doi: 10.1158/1078-0432.CCR-18-0041. Epub 2018 Apr 24. PMID: 29691296; PMCID: PMC6591719. 3. Xie T, Lv T, Zhang T, Feng D, Zhu F, Xu Y, Zhang L, Gu L, Guo Z, Ding C, Gong J. Interleukin-6 promotes skeletal muscle catabolism by activating tryptophan-indoleamine 2,3-dioxygenase 1-kynurenine pathway during intra-abdominal sepsis. J Cachexia Sarcopenia Muscle. 2023 Mar 7. doi: 10.1002/jcsm.13193. Epub ahead of print. PMID: 36880228. 4. Meng X, Du G, Ye L, Sun S, Liu Q, Wang H, Wang W, Wu Z, Tian J. Combinatorial antitumor effects of indoleamine 2,3-dioxygenase inhibitor NLG919 and paclitaxel in a murine B16-F10 melanoma model. Int J Immunopathol Pharmacol. 2017 Sep;30(3):215-226. doi: 10.1177/0394632017714696. Epub 2017 Jun 12. PMID: 28604143; PMCID: PMC5815254.

In vitro protocol:

In vivo protocol:

1. Xie T, Lv T, Zhang T, Feng D, Zhu F, Xu Y, Zhang L, Gu L, Guo Z, Ding C, Gong J. Interleukin-6 promotes skeletal muscle catabolism by activating tryptophan-indoleamine 2,3-dioxygenase 1-kynurenine pathway during intra-abdominal sepsis. J Cachexia Sarcopenia Muscle. 2023 Mar 7. doi: 10.1002/jcsm.13193. Epub ahead of print. PMID: 36880228. 2. Meng X, Du G, Ye L, Sun S, Liu Q, Wang H, Wang W, Wu Z, Tian J. Combinatorial antitumor effects of indoleamine 2,3-dioxygenase inhibitor NLG919 and paclitaxel in a murine B16-F10 melanoma model. Int J Immunopathol Pharmacol. 2017 Sep;30(3):215-226. doi: 10.1177/0394632017714696. Epub 2017 Jun 12. PMID: 28604143; PMCID: PMC5815254.

1: St-Jean F, Angelaud R, Bachmann S, Carrera DE, Remarchuk T, Piechowicz KA, Niedermann K, Iding H, Meier R, Hou H, Sirois LE, Xu J, Olbrich M, Rege P, Guillemot-Plass M, Gosselin F. Stereoselective Synthesis of the IDO Inhibitor Navoximod. J Org Chem. 2022 Apr 1;87(7):4955-4960. doi: 10.1021/acs.joc.1c02994. Epub 2022 Mar 23. PMID: 35317556. 2: Zhuang Q, Zhao B, Lin Z, Liang Y, Zhao Q, Wang Y, Liao N, Tu H, Zheng Y, Chen H, Zeng Y, Zhang D, Liu X. Navoximod modulates local HSV-1 replication to reshape tumor immune microenvironment for enhanced immunotherapy via an injectable hydrogel. Commun Biol. 2023 Jun 9;6(1):621. doi: 10.1038/s42003-023-04983-z. PMID: 37296221; PMCID: PMC10256817. 3: Chen F, Zhao D, Huang Y, Wen X, Feng S. Synergetic impact of combined navoximod with cisplatin mitigates chemo-immune resistance via blockading IDO1⁺ CAFs-secreted Kyn/AhR/IL-6 and pol ζ-prevented CIN in human oral squamous cell carcinoma. Life Sci. 2023 Dec 15;335:122239. doi: 10.1016/j.lfs.2023.122239. Epub 2023 Nov 7. PMID: 37944638. 4: Ebata T, Shimizu T, Fujiwara Y, Tamura K, Kondo S, Iwasa S, Yonemori K, Shimomura A, Kitano S, Koyama T, Sato N, Nakai K, Inatani M, Yamamoto N. Phase I study of the indoleamine 2,3-dioxygenase 1 inhibitor navoximod (GDC-0919) as monotherapy and in combination with the PD-L1 inhibitor atezolizumab in Japanese patients with advanced solid tumours. Invest New Drugs. 2020 Apr;38(2):468-477. doi: 10.1007/s10637-019-00787-3. Epub 2019 May 24. PMID: 31124055; PMCID: PMC7066107. 5: Ma S, Suchomel J, Yanez E, Yost E, Liang X, Zhu R, Le H, Siebers N, Joas L, Morley R, Royer-Joo S, Pirzkall A, Salphati L, Ware JA, Morrissey KM. Investigation of the absolute bioavailability and human mass balance of navoximod, a novel IDO1 inhibitor. Br J Clin Pharmacol. 2019 Aug;85(8):1751-1760. doi: 10.1111/bcp.13961. Epub 2019 Jun 14. PMID: 30973970; PMCID: PMC6624388. 6: Wang S, Ma S, Chen E, Wang J, Le H, Hanlon SP, Binder M, Lee W, Khojasteh SC, Salphati L. Mass Balance of the Indoleamine 2,3-Dioxygenase Inhibitor Navoximod (GDC-0919) in Rats and Dogs: Unexpected Cyanide Release from Imidazo[5,1-a]isoindole and Species Differences in Glucuronidation. Drug Metab Dispos. 2023 Jul;51(7):862-872. doi: 10.1124/dmd.123.001289. Epub 2023 Apr 14. PMID: 37059472. 7: Nayak-Kapoor A, Hao Z, Sadek R, Dobbins R, Marshall L, Vahanian NN, Jay Ramsey W, Kennedy E, Mautino MR, Link CJ, Lin RS, Royer-Joo S, Liang X, Salphati L, Morrissey KM, Mahrus S, McCall B, Pirzkall A, Munn DH, Janik JE, Khleif SN. Phase Ia study of the indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor navoximod (GDC-0919) in patients with recurrent advanced solid tumors. J Immunother Cancer. 2018 Jun 20;6(1):61. doi: 10.1186/s40425-018-0351-9. PMID: 29921320; PMCID: PMC6009946. 8: Jung KH, LoRusso P, Burris H, Gordon M, Bang YJ, Hellmann MD, Cervantes A, Ochoa de Olza M, Marabelle A, Hodi FS, Ahn MJ, Emens LA, Barlesi F, Hamid O, Calvo E, McDermott D, Soliman H, Rhee I, Lin R, Pourmohamad T, Suchomel J, Tsuhako A, Morrissey K, Mahrus S, Morley R, Pirzkall A, Davis SL. Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced Solid Tumors. Clin Cancer Res. 2019 Jun 1;25(11):3220-3228. doi: 10.1158/1078-0432.CCR-18-2740. Epub 2019 Feb 15. PMID: 30770348; PMCID: PMC7980952. 9: Kumar S, Waldo JP, Jaipuri FA, Marcinowicz A, Van Allen C, Adams J, Kesharwani T, Zhang X, Metz R, Oh AJ, Harris SF, Mautino MR. Discovery of Clinical Candidate (1R,4r)-4-((R)-2-((S)-6-Fluoro- 5H-imidazo[5,1-a]isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol (Navoximod), a Potent and Selective Inhibitor of Indoleamine 2,3-Dioxygenase 1. J Med Chem. 2019 Jul 25;62(14):6705-6733. doi: 10.1021/acs.jmedchem.9b00662. Epub 2019 Jul 2. PMID: 31264862.