Elunetirom

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Elunetirom

CAS 2156649-32-8

MF C19H21Cl2NO3 MW382.3 g/mol

2-[3,5-dichloro-4-[(4-hydroxy-3-propan-2-ylphenyl)methyl]phenoxy]-N-methylacetamide

2-(3,5-dichloro-4-{[4-hydroxy-3-(propan-2-yl)phenyl]methyl}phenoxy)-N-methylacetamide
thyroid hormone beta receptor agonist, ABX-002, MA-JD21, ABX 002, MA JD21, QTW4WC4BRX, MA-JD-21,

Elunetirom (ABX-002/MA-JD21) is an oral, brain-penetrant thyroid hormone receptor beta agonist being developed by Autobahn Therapeutics for major depressive disorder (MDD) and bipolar depression. As of early 2026, it is in Phase 2 clinical trials, aiming to treat these disorders with fewer peripheral side effects than traditional treatments.

Key Facts About Elunetirom

  • Mechanism: It is a prodrug converted into an active metabolite that selectively targets TR\(\beta \) in the central nervous system (CNS), boosting brain energy and plasticity.
  • Development Stage: Currently in Phase 2 trials for major depressive disorder (MDD) and bipolar depression.
  • Target Indications: Primarily for psychiatric conditions, with preclinical research for neurodegenerative diseases like multiple sclerosis and adrenomyeloneuropathy.
  • Benefits: Designed to offer a favorable safety profile compared to synthetic thyroid hormones, minimizing systemic side effects.

Clinical Status (2025–2026)
As of early 2026, Autobahn Therapeutics has reported positive Phase 1 data, confirming its, safety, tolerability, and ability to engage with brain targets.

  • Phase 2 Focus: Evaluating its potential as an add-on (adjunctive) therapy for depression.
  • Preclinical Findings: Studies suggest it may help repair myelin (remyelination) and treat cognitive impairment.

Elunetirom, also known by its developmental code names ABX-002 and MA-JD21, is a thyroid hormone receptor agonist which is under development for the treatment of major depressive disorder, bipolar depression, multiple sclerosis, and adrenomyeloneuropathy.[1][2] It is a prodrug of LL-340001 and acts as a potent, selective, and centrally penetrant agonist of the thyroid hormone receptor beta (TRβ).[1][2] The drug produces psychoplastogenic effects similar to those of brain-derived neurotrophic factor (BDNF) in rodents.[2] In addition, it has been found to improve cognitive impairment caused by old age or scopolamine treatment in rodents.[2] Eunetirom is under development by Autobahn Therapeutics.[1] As of December 2025, it is in phase 2 clinical trials for treatment of major depressive disorder and bipolar depression and is in the preclinical research stage of development for multiple sclerosis and adrenomyeloneuropathy.[1]

SYN

[WO2022236133A1]

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2022236133&_cid=P21-MP3GH3-29154-1

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2017201320&_cid=P21-MP3GLZ-35721-1

xample 16. Preparation of 2-(3. 5-dichloro-4-(4-hvdroxy-3-isopropylbenzyl) phenoxy)-N-methylacetamide (MA-JD21; 10b)

0142] 2-(3, 5-dichloro-4-(4-hydroxy-3-isopropylbenzyl) phenoxy) acetic acid (100 mg, 0.27 mmol, 1 equiv.) was dissolved in methanol (5 mL) in a sealed tube. Sulfuric acid (1 drop) added to it and the reaction was sealed and heated to 65°C for one hour while stirring. It was cooled to room temperature and TLC analysis (ethyl acetate: hexane 1 : 1) shows complete conversion to the intermediate methyl ester. To this was then added 40% methyl amine in water (320μ1, 4mmol, 15 equiv.). The reaction is resealed and heated to 65°C for one hour. The reaction flask was cooled to room temperature and sodium hydroxide (0.5N, 10 mL) added to it. The reaction product was extracted with dichoromethane (3 x 50 mL). The organic layers were combined, dried on anhydrous Mg2S04, filtered and concentrated. Purification by flash chromatography (50% hexane in ethylacetate) gave the product as a white solid (65 mg, 0.17 mmol, 63%). XH NMR (400 MHz, MeOH-c¾): 5=7.12 (s, 2H), 7.01 (d, IH, J=1.98Hz), 6.77 (dd, IH, J=8.21Hz, 2.26Hz), 6.62 (d, IH, J=8.21Hz), 4.56 (s, 2H), 4.15 (s, 2H), 3.23 (septet, IH, J=7.14Hz), 2.85 (s, 3H), 1.17 (d, 6H, J= 6.93Hz). HRMS exact mass calculated for C19H21CI2NO3 [M + H] +: m/z 384.09455, found m/z 384.09473.

PAT

ADVT

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References

References

  1.  “Autobahn Therapeutics”. AdisInsight. 2 December 2025. Retrieved 7 January 2026.
  2.  Harris J, Baccei J, Franey B, Vivian JA, MacKenna D, Stratton W, et al. (January 2026). “ACNP 64th Annual Meeting: Poster Abstracts P584-P872”. Neuropsychopharmacology. 51 (Suppl 1). Nature Publishing Group: 410–571. doi:10.1038/s41386-025-02281-2. PMID 41507446.

Clinical data
Other namesABX-002; ABX002; MA-JD21; MA-JD-21
Routes of
administration		Oral[1]
Drug classThyromimetic; Thyroid hormone receptor beta (TRβ) agonist
Identifiers
IUPAC name
CAS Number2156649-32-8
PubChem CID132160637
DrugBankDB18157
ChemSpider129433137
UNIIQTW4WC4BRX
KEGGD13273
ChEMBLChEMBL5314909
Chemical and physical data
FormulaC19H21Cl2NO3
Molar mass382.28 g·mol−1
3D model (JSmol)Interactive image
SMILES
InChI

///////////elunetirom, ANAX LABS, thyroid hormone beta receptor agonist, ABX-002, MA-JD21, ABX 002, MA JD21, QTW4WC4BRX, MA-JD-21,

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