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

• Derivatives of sobetiromePublication Number: US-10870616-B2Priority Date: 2016-05-18Grant Date: 2020-12-22
• Process for the preparation of derivatives of sobetiromePublication Number: EP-3936497-A1Priority Date: 2016-05-18
• Subiterol DerivativesPublication Number: CN-113277958-APriority Date: 2016-05-18
• Sobetarom derivativePublication Number: JP-6982004-B2Priority Date: 2016-05-18Grant Date: 2021-12-17
• Derivatives of sobetiromePublication Number: US-2019210950-A1Priority Date: 2016-05-18
• History of SubtirumPublication Number: IL-263050-APriority Date: 2016-05-18
• Derivatives of sorbetyromPublication Number: KR-102331596-B1Priority Date: 2016-05-18Grant Date: 2021-11-25
• Derivatives of sobetiromePublication Number: EP-3457851-B1Priority Date: 2016-05-18Grant Date: 2021-06-23
• Fatty acid amide hydrolase (faah) cleavable prodrugs of thyromimetics and combination with peripherally restricted faah inhibitorsPublication Number: EP-4333844-A1Priority Date: 2021-05-06
• Isotopic thyromimetic compoundsPublication Number: US-2023348364-A1Priority Date: 2020-06-03
• Sobetarom derivativePublication Number: JP-2022033788-APriority Date: 2016-05-18
• Derivatives of sobetiromePublication Number: AU-2017267734-A1Priority Date: 2016-05-18
• Derivatives of sobetiromePublication Number: WO-2017201320-A1Priority Date: 2016-05-18
• Fatty acid amide hydrolase (faah) cleavable prodrugs of thyromimetics and combination with peripherally restricted faah inhibitorsPublication Number: US-2024254075-A1Priority Date: 2021-05-06
• Fatty acid amide hydrolase (FAAH) cleaves prodrugs of thyroxine drugs and combinations with peripherally restricted FAAH inhibitorsPublication Number: CN-117597122-APriority Date: 2021-05-06
• Fatty acid amide hydrolase (faah) cleavable prodrugs of thyromimetics and combination with peripherally restricted faah inhibitorsPublication Number: WO-2022236133-A1Priority Date: 2021-05-06
• Fatty acid amide hydrolase (faah) cleavable prodrugs of thyromimetics and combination with peripherally restricted faah inhibitorsPublication Number: AU-2022271304-A1Priority Date: 2021-05-06
• Fatty acid amide hydrolase (faah) cleavable prodrugs of thyromimetics and combination with peripherally restricted faah inhibitorsPublication Number: CA-3217789-A1Priority Date: 2021-05-06

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 names	ABX-002; ABX002; MA-JD21; MA-JD-21
Routes of administration	Oral[1]
Drug class	Thyromimetic; Thyroid hormone receptor beta (TRβ) agonist
Identifiers
IUPAC name
CAS Number	2156649-32-8
PubChem CID	132160637
DrugBank	DB18157
ChemSpider	129433137
UNII	QTW4WC4BRX
KEGG	D13273
ChEMBL	ChEMBL5314909
Chemical and physical data
Formula	C19H21Cl2NO3
Molar mass	382.28 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,