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Thursday, 8 October 2026

Sumonerimod

 

Sumonerimod

CAS 2433782-42-2

MFC25H26F3NO3 MW445.5

3-(5-((4-cyclopentyl-3-(trifluoromethyl)benzyl)oxy)-3-methyl-1H-indol-2-yl)propanoic acid,

3-(5-{[4-cyclopentyl-3-(trifluoromethyl)phenyl]methoxy}-3-methyl-1Hindol-2-yl)propanoic acid
sphingosine-1-phosphate receptor 1 agonist, immunomodulator, S1P1 agonist 6, 49KZ2L5DUV, CBP-307, Icanbelimod, CBP 307

Sumonerimod is a selective Sphingosine-1-phosphate receptor 1 ($\text{S1P}_1$) agonist developed primarily for autoimmune and inflammatory diseases (such as ulcerative colitis and Crohn's disease).

PAT

WO2020114475A1

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2020114475&_cid=P12-MUZ8I1-71620-1

Reference Example 72: Preparation of Intermediate I-74

ntermediate I-73 (4.3 g) was dissolved in dichloromethane (30 mL). The reaction mixture was cooled to -40 °C, and a dichloromethane solution (50 mL) of N-bromosuccinimide (NBS, 1.98 g, 11.1 mmol) was slowly added dropwise. After the addition was complete, the reaction mixture was heated to 0 °C and stirred at 0 °C for 2 h. The reaction mixture was washed with water (20 mL), the organic phase was separated, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by silica gel chromatography to obtain intermediate I-74.

[0395]

LC-MS(ESI)[M-H] -464。

[0396]Reference Example 73: Preparation of Intermediate I-75

Intermediate I-74 (1.0 g, 2.15 mmol) was dissolved in a mixture of 1,4-dioxane and water (10 mL, 4:1) at room temperature, followed by the addition of methylboric acid (1.29 g, 21.46 mmol), potassium carbonate (0.89 g, 6.44 mmol), and tetrakis(triphenylphosphine)palladium (243 mg, 0.21 mmol). The reaction mixture was stirred at 90 °C for 7 h under argon protection. The reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure to obtain the residue. The residue was dissolved in dichloromethane (20 mL), and water (10 mL) was added. The aqueous phase was separated and extracted with dichloromethane (20 mL × 2). The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the residue. The residue was purified by silica gel chromatography to obtain intermediate I-75.

[0399]

LC-MS(ESI)[M-H] -400.0.

[0400]Reference Example 74: Preparation of Intermediate I-76

Intermediate I-75 (470 mg, 1.17 mmol) was dissolved in tetrahydrofuran (10 mL) at room temperature, and ethoxycarbonylmethylene triphenylphosphine (490 mg, 1.41 mmol) was added. The reaction mixture was stirred at 80 °C for 15 h. After cooling the reaction solution to room temperature, the organic solvent was removed by concentration under reduced pressure to obtain the residue. The residue was purified by reversed-phase preparative liquid chromatography to obtain intermediate I-76.

[0403]

LC-MS(ESI)[M-H] -470.2.

[0404]Reference Example 75: Preparation of Intermediate I-77

Intermediate I-76 (110 mg, 0.23 mmol) was dissolved in ethyl acetate (2 mL), and PtO₂ (50 mg) was added

. The reaction mixture was stirred at room temperature for 2 h under a hydrogen atmosphere. After filtration, the filtrate was concentrated under reduced pressure to give intermediate I-77.

[0407]

LC-MS(ESI)[M+H] +474.2.

Example 16: Preparation of Compound 16

Intermediate I-77 (110 mg) was dissolved in tetrahydrofuran (2 mL), and lithium hydroxide monohydrate (29 mg, 0.70 mmol) and water (0.5 mL) were added. After stirring at room temperature for 3 h, the reaction solution was purified by preparative liquid chromatography to obtain compound 16.

[0809]

LC-MS(ESI)[M-H] -444.1.

[0810]

1H NMR(400MHz,MeOH-d 4)δ7.71(s,1H),7.66(d,J=8.2Hz,1H),7.57(d,J=8.2Hz,1H),7.13(d,J=8.7Hz,1H),6.98(d,J=2.3Hz,1H),6.76(dd,J=8.7,2.4Hz,1H),5.10(s,2H),3.41–3.35(m,1H),3.00(t,J=7.7Hz,2H),2.63(t,J=7.7Hz,2H),2.18(s,3H),2.10–2.02(m,2H),1.95–1.86(m,2H),1.78–1.60(m,4H).

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References

///////////sumonerimod, anax labs, sphingosine-1-phosphate receptor 1 agonist, immunomodulator, S1P1 agonist 6, 49KZ2L5DUV, CBP-307, Icanbelimod, CBP 307

#sumonerimod, #anax labs, #sphingosine-1-phosphate receptor 1 agonist, #immunomodulator, #S1P1 agonist 6, #49KZ2L5DUV, #CBP-307, #Icanbelimod, #CBP 307

Saturday, 3 October 2026

Sosimerasib

 

Sosimerasib

Cas 2839563-01-6

MF C36H39ClFN7O4 MW688.2 g/mol

(4R,7R)-16-chloro-9-[2-(dimethylamino)ethyl]-15-(2-fluoro-6-hydroxyphenyl)-4-methyl-12-(4-methyl-2-propan-2-yl-3-pyridinyl)-5-prop-2-enoyl-2,5,9,12,14-pentazatetracyclo[8.8.0.02,7.013,18]octadeca-1(10),13,15,17-tetraene-8,11-dione

(2R,4aR,8M)-11-chloro-6-[2-(dimethylamino)ethyl]-10-(2-fluoro-6-hydroxyphenyl)-2-methyl-8-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-3-(prop-2-enoyl)-2,3,4,4a,6,8-hexahydro-1Hpyrazino[1',2':4,5]pyrazino[2,3-c][1,8]naphthyridine-5,7-dione
Kirsten rat sarcoma viral oncogene homolog inhibitor, antineoplastic, HBI-2438, JMKX1899, HBI 2438, JMKX 1899, 2VHH89PP6W

Sosimerasib is an orally active KRASG12C inhibitor. Sosimerasib can be used in research related to non-small cell lung cancer.

Sosimerasib (also known as HBI-2438 or JMKX1899) is an orally active, covalent small molecule inhibitor that targets the KRAS G12C mutation. Developed natively in China, it secured conditional marketing approval from the National Medical Products Administration (NMPA) in February 2026, making it China's first domestically discovered and registered KRAS G12C inhibitor.

The drug is designed to selectively lock the mutant KRAS protein in its inactive, GDP-bound state, preventing downstream oncogenic signaling pathways that drive tumor growth.

Mechanism and Clinical Indications

Sosimerasib specifically binds to the cysteine residue at position 12 of the mutated KRAS protein. It has shown distinct clinical advantages, including central nervous system (CNS) penetration, which makes it effective against brain metastases. Its primary therapeutic applications include:

  • Non-Small Cell Lung Cancer (NSCLC): It is indicated for patients with locally advanced or metastatic non-squamous NSCLC harboring the KRAS G12C mutation, particularly those who have progressed after receiving standard platinum-based chemotherapy or immune checkpoint inhibitors.
  • Colorectal Cancer (CRC) and Solid Tumors: It is being clinically evaluated as a monotherapy or combination treatment for other advanced solid tumors, showing promising anti-tumor activity in KRAS G12C-mutated colorectal cancer.

Efficacy Data

Data presented across recent oncology conferences highlight substantial therapeutic efficacy:

  • NSCLC Outcomes: In a pivotal Phase II trial involving 145 previously treated patients, a once-daily 500 mg dose of sosimerasib achieved an Objective Response Rate (ORR) of 52.4% and a Disease Control Rate (DCR) of 87.6%. The median progression-free survival (PFS) was documented at 7.2 months.
  • Colorectal Cancer Outcomes: Data from the 2026 ASCO Annual Meeting for advanced CRC patients demonstrated a confirmed ORR of 31.6% and a median PFS of 8.3 months.

Safety and Side Effects

Sosimerasib possesses a manageable safety profile, with rare occurrences of treatment discontinuations (around 1.8% to 2.1%) due to toxicity. The most common treatment-related adverse events (TRAEs) include:

  • Elevated liver enzymes (Alanine aminotransferase/ALT and Aspartate aminotransferase/AST increases)
  • Anaemia
  • Decreased white blood cell count or elevated gamma-glutamyl transferase

Commercial and Development Background

The compound was originally discovered by Shanghai Jiyu Pharmaceutical Technology. It is being co-developed and commercialized through partnerships with HUYA Bioscience International (Huyabio) and Zhejiang Hangyu Pharmaceutical. Within the Chinese market, it joins foreign-developed alternatives like sotorasib (Amgen) and adagrasib (Bristol Myers Squibb), marking a major milestone for independent biomedical innovation in the region. Ongoing Phase III trials are evaluating sosimerasib in combination regimens (such as with the FAK inhibitor IN10018) as a first-line treatment option.

PAT

[US20220389029]

https://patentscope.wipo.int/search/en/detail.jsf?docId=US380594568&_cid=P20-MUT7JP-65582-1

Embodiment 29: Preparation of Compound 29

      Step 1: Preparation of Compound 29-1
 Compound 25-3 (700 mg, 1 mmol) and cesium carbonate (977 mg, 3 mmol) were dissolved in N,N-dimethylformamide (20 mL), and compound 26-1 (432 mg, 3 mmol) was added thereto at room temperature (25° C.). After the addition was completed, under nitrogen atmosphere, the system was heated to 120° C. and stirred for 2 hours. The system was filtered and concentrated to obtain a crude product, the crude product was purified by silica gel column chromatography (dichloromethane/methanol (v/v)=1/10) to obtain compound 29-1.
      MS (ESI) m/z (M+H) +=778.2.
      Step 2: Preparation of Compound 29-2
 Compound 29-1 (150 mg, 0.2 mmol), hydrochloric acid (6N, 7 mL) were added to a mixed solution of methanol (0.6 mL) and tetrahydrofuran (6 mL). The system was heated to 55° C. and stirred for 10 min. The system was concentrated to obtain crude product compound 29-2, which was directly used in the next reaction without further purification.
      MS (ESI) m/z (M+H) +=634.2.
      Step 3: Preparation of Compound 29
 Compound 29-2 (140 mg, 0.2 mmol) was dissolved in dichloromethane (10 mL), and the system was cooled to 0° C., triethylamine (0.3 mL, 2.1 mmol) and acryloyl chloride (27 mg, 0.3 mmol) were added dropwise thereto, the reaction was carried out at 0° C. for 0.5 hours. The system was quenched with methanol and then concentrated to obtain a crude product. The crude product was dissolved in methanol (5 mL), potassium carbonate (140 mg) was added thereto, after the addition was completed, the system was stirred at room temperature (20° C.) for 30 min. The pH of the system was adjusted to 6 with hydrochloric acid, the mixture was extracted with dichloromethane (20 mL) and water (20 mL); and the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product, the crude product was purified by high performance liquid chromatography (separation conditions: chromatographic column Welch Xtimate® C18 21.2×250 mm, 10 μm; column temperature: 25° C., mobile phase: water (10 mM/L NH 4HCO 3)-acetonitrile; acetonitrile 40%-60% 9 min; flow rate 30 mL/min) to obtain compound 29.
      MS (ESI) m/z (M+H) +=688.2.
      Step 4: Preparation of Compounds 29A and 29B
  Diastereoisomeric compound 29 was purified by SFC («Column_3»; mobile phase: [CO 2-ethanol (0.1% ammonia)]; ethanol %: 25%; flow rate: 60 mL/min; column temperature: 38° C.). After concentration, compound 29A and compound 29B were obtained.
      Compound 29A:
      1H NMR (400 MHz, DMSO-d 6) δ 10.06 (brs, 1H), 8.37 (d, J=4.9 Hz, 1H), 8.18 (s, 1H), 7.29-7.05 (m, 2H), 6.97 (dd, J=16.8, 10.6 Hz, 0.75H), 6.79 (dd, J=16.7, 10.7 Hz, 0.25H), 6.69-6.46 (m, 2H), 6.07 (dd, J=16.8, 2.5 Hz, 1H), 5.68 (dd, J=10.5, 2.4 Hz, 1H), 4.95 (d, J=13.9 Hz, 0.25H), 4.82-4.66 (m, 0.75H), 4.54 (d, J=14.0 Hz, 1H), 4.40-4.12 (m, 2H), 3.94 (dd, J=20.5, 4.4 Hz, 1H), 3.68 (dd, J=14.2, 4.4 Hz, 1H), 3.14-2.90 (m, 1H), 2.43-2.34 (m, 2H), 2.27-2.08 (m, 2H), 1.97-1.82 (m, 9H), 1.56-1.45 (m, 3H), 0.97 (dd, J=6.6, 2.2 Hz, 3H), 0.78 (t, J=6.0 Hz, 3H).
      MS (ESI) m/z (M+H) +=688.3.
      SFC 100% ee. Retention time was 3.559 min.
      Separation conditions: chromatographic column: «Column_2»; mobile phase: [CO 2-ethanol (0.05% DEA)]; ethanol %: 5%-40% 5 min, 40% 2.5 min, 5% 2.5 min; flow rate: 2.5 mL/min; column temperature: 35° C.
      Compound 29B:
      1H NMR (400 MHz, DMSO-d 6) δ 10.18 (brs, 1H), 8.45 (d, J=4.9 Hz, 1H), 8.26 (s, 1H), 7.29-7.20 (m, 2H), 7.04 (dd, J=16.8, 10.4 Hz, 0.75H), 6.86 (dd, J=17.6, 10.4 Hz, 0.25H), 6.72-6.60 (m, 2H), 6.14 (d, J=16.4 Hz, 1H), 5.75 (d, J=10.7 Hz, 1H), 5.03 (d, J=13.8 Hz, 0.25H), 4.80 (d, J=7.8 Hz, 0.75H), 4.61 (d, J=14.1 Hz, 1H), 4.43-4.30 (m, 1H), 4.28-4.15 (m, 1H), 4.04-3.89 (m, 1H), 3.75 (dd, J=14.5, 4.4 Hz, 1H), 3.28-3.10 (m, 2H), 2.75-2.65 (m, 1H), 2.39-2.28 (m, 1H), 2.28-2.17 (m, 1H), 2.06-1.96 (m, 6H), 1.81 (d, J=9.5 Hz, 3H), 1.53 (d, J=6.8 Hz, 3H), 1.11 (d, J=6.9 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H).
      MS (ESI) m/z (M+H) +=688.3.
      HPLC retention time was 5.269 min.
      Separation conditions: chromatographic column: Waters XBridge 4.6*100 mm, 3.5 μm; column temperature: 40° C.; mobile phase: water (10 mM ammonium bicarbonate)-acetonitrile; acetonitrile: 5%-95% 7 min; flow rate: 1.2 mL/min. SFC 100% ee. Retention time was 4.349 min.
      Separation conditions: chromatographic column: «Column_2»; mobile phase: [CO 2-ethanol (0.05% DEA)]; ethanol %: 5%-40% 5 min, 40% 2.5 min, 5% 2.5 min; flow rate: 2.5 mL/min; column temperature: 35° C.

PAT

US20230227472

https://patentscope.wipo.int/search/en/detail.jsf?docId=US402823590&_cid=P20-MUT7F9-60174-1

Step 3: Preparation of Compound 29

Compound 29-2 (140 mg, 0.2 mmol) was dissolved in dichloromethane (10 mL), and the system was cooled to 0° C., triethylamine (0.3 mL, 2.1 mmol) and acryloyl chloride (27 mg, 0.3 mmol) were added dropwise thereto, the reaction was carried out at 0° C. for 0.5 hours. The system was quenched with methanol and then concentrated to obtain a crude product. The crude product was dissolved in methanol (5 mL), potassium carbonate (140 mg) was added thereto, after the addition was completed, the system was stirred at room temperature (20° C.) for 30 min. The pH of the system was adjusted to 6 with hydrochloric acid, the mixture was extracted with dichloromethane (20 mL) and water (20 mL); and the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product, the crude product was purified by high performance liquid chromatography (separation conditions: chromatographic column Welch Xtimate® C18 21.2×250 mm, 10 μm; column temperature: 25° C., mobile phase: water (10 mM/L NH 4HCO 3)-acetonitrile; acetonitrile 40%-60% 9 min; flow rate 30 mL/min) to obtain compound 29.
      MS (ESI) m/z (M+H) +=688.2.

Step 4: Preparation of Compounds 29A and 29B

Diastereoisomeric compound 29 was purified by SFC («Column_3»; mobile phase: [CO 2-ethanol (0.1% ammonia)]; ethanol %: 25%; flow rate: 60 mL/min; column temperature: 38° C.). After concentration, compound 29A and compound 29B were obtained.

Compound 29A:

      1H NMR (400 MHz, DMSO-d 6) δ 10.06 (brs, 1H), 8.37 (d, J=4.9 Hz, 1H), 8.18 (s, 1H), 7.29-7.05 (m, 2H), 6.97 (dd, J=16.8, 10.6 Hz, 0.75H), 6.79 (dd, J=16.7, 10.7 Hz, 0.25H), 6.69-6.46 (m, 2H), 6.07 (dd, J=16.8, 2.5 Hz, 1H), 5.68 (dd, J=10.5, 2.4 Hz, 1H), 4.95 (d, J=13.9 Hz, 0.25H), 4.82-4.66 (m, 0.75H), 4.54 (d, J=14.0 Hz, 1H), 4.40-4.12 (m, 2H), 3.94 (dd, J=20.5, 4.4 Hz, 1H), 3.68 (dd, J=14.2, 4.4 Hz, 1H), 3.14-2.90 (m, 1H), 2.43-2.34 (m, 2H), 2.27-2.08 (m, 2H), 1.97-1.82 (m, 9H), 1.56-1.45 (m, 3H), 0.97 (dd, J=6.6, 2.2 Hz, 3H), 0.78 (t, J=6.0 Hz, 3H).
      MS (ESI) m/z (M+H) +=688.3.
      SFC 100% ee. Retention time was 3.559 min.
      Separation conditions: chromatographic column: «Column_2»; mobile phase: [CO 2-ethanol (0.05% DEA)]; ethanol %: 5%-40% 5 min, 40% 2.5 min, 5% 2.5 min; flow rate: 2.5 mL/min; column temperature: 35° C.

Compound 29B:

      1H NMR (400 MHz, DMSO-d 6) δ 10.18 (brs, 1H), 8.45 (d, J=4.9 Hz, 1H), 8.26 (s, 1H), 7.29-7.20 (m, 2H), 7.04 (dd, J=16.8, 10.4 Hz, 0.75H), 6.86 (dd, J=17.6, 10.4 Hz, 0.25H), 6.72-6.60 (m, 2H), 6.14 (d, J=16.4 Hz, 1H), 5.75 (d, J=10.7 Hz, 1H), 5.03 (d, J=13.8 Hz, 0.25H), 4.80 (d, J=7.8 Hz, 0.75H), 4.61 (d, J=14.1 Hz, 1H), 4.43-4.30 (m, 1H), 4.28-4.15 (m, 1H), 4.04-3.89 (m, 1H), 3.75 (dd, J=14.5, 4.4 Hz, 1H), 3.28-3.10 (m, 2H), 2.75-2.65 (m, 1H), 2.39-2.28 (m, 1H), 2.28-2.17 (m, 1H), 2.06-1.96 (m, 6H), 1.81 (d, J=9.5 Hz, 3H), 1.53 (d, J=6.8 Hz, 3H), 1.11 (d, J=6.9 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H).
      MS (ESI) m/z (M+H) +=688.3.
      HPLC retention time was 5.269 min.
      Separation conditions: chromatographic column: Waters XBridge 4.6*100 mm, 3.5 μm; column temperature: 40° C.; mobile phase: water (10 mM ammonium bicarbonate)-acetonitrile; acetonitrile: 5%-95% 7 min; flow rate: 1.2 mL/min. SFC 100% ee. Retention time was 4.349 min.
      Separation conditions: chromatographic column: «Column_2»; mobile phase: [CO 2-ethanol (0.05% DEA)]; ethanol %: 5%-40% 5 min, 40% 2.5 min, 5% 2.5 min; flow rate: 2.5 mL/min; column temperature: 35° C.

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References

[1]. Jia Zhong, et al. Sosimerasib monotherapy in patients with previously treated KRAS G12C–mutated non-small cell lung cancer: Primary results of a phase 2 study. Journal of Clinical Oncology Volume 43, Number 16_suppl June 2025.

///////////sosimerasib, anax labs, Kirsten rat sarcoma viral oncogene homolog inhibitor, antineoplastic, HBI-2438, JMKX1899, HBI 2438, JMKX 1899, 2VHH89PP6W

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Thursday, 1 October 2026

Tiratricol

 

Tiratricol

CAS 51-24-1, 1477-04-9 (hydrochloride salt)

MFC14H9I3O4 MW621.93 g/mol

9/28/2026, Emcitate, FDA 2026, APPROVALS 2026, Triac

2-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]acetic acid

  • 3,3',5-TRIIODOTHYROACETIC ACID
  • Triiodothyroacetic acid

To treat peripheral thyrotoxicosis in patients with MCT8 deficiency

Tiratricol is a monocarboxylic acid that is (4-hydroxy-3,5-diiodophenyl)acetic acid in which the phenolic hydroxy group has been replaced by a 4-hydroxy-3-iodophenoxy group. It is a thyroid hormone analogue that has been used in the treatment of thyroid hormone resistance syndrome. It has a role as an antiviral agent, a nutraceutical, a thyroid hormone, an anti-obesity agent, an EC 1.3.5.2 [dihydroorotate dehydrogenase (quinone)] inhibitor and a human metabolite. It is a monocarboxylic acid, a member of phenols, an aromatic ether and an organoiodine compound

Tiratricol (also known as TRIAC or triiodothyroacetic acid), sold under the brand name Emcitate, is a thyroid hormone analogue. Triiodothyroacetic acid is also a physiologic thyroid hormone that is present in the normal organism in low concentrations. Tiratricol is an analogue of a naturally circulating metabolite of the active thyroid hormone T3.[1] MCT8 is a specific thyroid hormone transporter.[1] While T3 and T4 thyroid hormones rely on MCT8 to enter several tissues such as the brain, tiratricol can enter cells independently of MCT8.[1] Once inside cells, tiratricol activates the thyroid hormone receptor in a similar way to endogenous T3.[1]

The most common side effects are excessive sweating, irritability, anxiety and nightmares.[1]

Medical uses

Tiratricol is indicated in the management of thyroid hormone resistance syndrome.[3]

In the United States, Tiratricol is indicated for the treatment of peripheral thyrotoxicosis in adults and pediatric patients with MCT8 deficiency (Allan–Herndon–Dudley syndrome).[4][5]

Society and culture

Legal status

Tiratricol is not approved for sale in Canada. It was once an approved medication in Brazil, but its marketing authorization was suspended in 2003, effectively prohibiting its sale.[6] Tiratricol is available in France for therapy of thyroid hormone resistance and adjuvant therapy of thyroid cancer.[7]

In December 2024, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Emcitate, intended for the treatment of MCT8 deficiency (Allan-Herndon-Dudley syndrome).[1][8] The applicant for this medicinal product is Rare Thyroid Therapeutics International AB.[1] Emcitate is a hybrid medicine of Téatrois, which has been authorized in France.[1] Emcitate contains the same active substance as Téatrois but has a different indication.[1] Tiratricol was authorized for medical use in the European Union in February 2025.[1][2] Tiratricol was approved for medical use in the United States kn September 2026.[5]

Research

Tiratricol has been investigated for use in reducing goiter.[9]

It has also shown some effectiveness in reducing the atrophy caused when using corticosteroids.[10]

Tiratricol has also been widely marketed, under various trade names, as a weight loss aid. In 1999 and 2000, the United States Food and Drug Administration and Health Canada both issued warnings to the public regarding the use of dietary supplements containing tiratricol.[11][12]

LIT

C. E. Wilkinson (Biochem. J. 63, 601, 1956): The primary landmark study describing the controlled iodination approach to yield triiodothyroacetic acid.

Meltzer et al. (J. Org. Chem. 26, 1418, 1961): Advanced methods for the synthesis and purification of thyroacetic acid derivatives.

PAT

British Patent GB 803149 (1958)

https://patentscope.wipo.int/search/en/detail.jsf?docId=GB134699786&_cid=P10-MUQCJP-66503-1

EXAMPLE 1 3:5:31 - triiodo - 4 - (41 - hydroxyphenoxy)
phenyl acetic acid (Triac)
An aqueous solution of iodine (N: 40 mls.) was added dropwise with stirring during hour to a solution of 3:5-diiodo-4-(41hydroxyphenoxy)phenyl acetic acid (Diac) (9.92 g.; 0.02 mol.) in aqueous ethylamine (33%: 120 mls.). After a further hour the solution was acidified with hydrochloric acid (5N) at 10-15 (ice-bath cooling). The precipitate, which became gummy on filtration, was triturated with water containing a few drops of hydrochloric acid and again filtered.

The solid was then ground with water containing a little hydrochloric acid, filtered, washed with water and dried over phosphorus pentoxide (12.10 g.; m.p. 161-72 ). The crude product was dissolved in methanol (240 mls.) and stirred during the dropwise addition of water (180 mls.). After standing overnight, the mixture was decanted from the tarry material which had separated. Water (60 mls.) was added in one portion, and the milky solution allowed to stand several hours until crystallisation was complete. The product was collected and dried over phosphorus pentoxide, 7.1 g. (63%) m.p. 181-3 (after sinteringg at about 60 , effervescing at 100 and resolidifying at about 115 ). A sample from a previous experiment was dried by heating slowly to 100 in high vacuum over phosphorus pentoxide. Found: C, 27.3; H, 1.5; I, 61.2, C14H9O4I3 requires C, 27.0; H, 1.5; I, 61.2%.

To prepare the sodium salt of Triac 42.8 g. of Triac was dissolved in a hot solution of sodium carbonate (7.3 g.) in water (420 mis.) and filtered. A solution of salt (35%; 42 mis.) was added and the mixture cooled, finally in the refrigerator. The product was collected and dried to constant weight over phosphorus pentoxide (34.1 g.).

PAT

British Patent GB 805761 (1958)

PAT

US Patent US8071134B2

https://patentscope.wipo.int/search/en/detail.jsf?docId=US42563548&_cid=P10-MUQCHB-64862-1

PAT

Chinese Patent CN113181152B

https://patentscope.wipo.int/search/en/detail.jsf?docId=CN333439736&_cid=P10-MUQCEZ-62879-1

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References

  1. "Emcitate EPAR". European Medicines Agency (EMA). 12 December 2024. Retrieved 16 December 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  2. "Emcitate PI". Union Register of medicinal products. 17 February 2025. Retrieved 27 February 2025.
  3. Carvalho GA, Ramos HE (2004). "[Thyroid hormone resistance syndrome]" (PDF). Arq Bras Endocrinol Metabol (in Portuguese). 48 (1): 83–92. doi:10.1590/S0004-27302004000100010. PMID 15611821.
  4. "EMCITATE — Now Approved". EMCITATE® — Now Approved. Retrieved 29 September 2026.
  5. "Egetis Therapeutics Announces U.S. FDA Approval of EMCITATE® (tiratricol) for Patients with MCT8 Deficiency". Egetis Therapeutics. Retrieved 29 September 2026.
  6. "Anvisa suspende Tiratricol" (in Portuguese). Brazilian Society of Endocrinology and Metabolism. Archived from the original on 9 October 2007. Retrieved 8 August 2007.
  7. Laboratoires DB PHARMA: Teatrois Deprecated link archived 2015-01-19 at archive.today information
  8. "First treatment for peripheral thyrotoxicosis in patients with Allan-Herndon-Dudley syndrome". European Medicines Agency (EMA) (Press release). 13 December 2024. Retrieved 16 December 2024.
  9. Brenta G, Schnitman M, Fretes O, et al. (November 2003). "Comparative efficacy and side effects of the treatment of euthyroid goiter with levo-thyroxine or triiodothyroacetic acid". J. Clin. Endocrinol. Metab. 88 (11): 5287–92. doi:10.1210/jc.2003-030095. PMID 14602763.
  10. Yazdanparast P, Carlsson B, Oikarinen A, Risteli J, Lavin T, Faergemann J (November 2006). "Action of topical thyroid hormone analogue, triiodothyroacetic acid in reversing glucocorticoid-induced skin atrophy in humans". Thyroid. 16 (11): 1157–62. doi:10.1089/thy.2006.16.1157. PMID 17123343.
  11. "FDA Warns Against Consuming Dietary Supplements Containing Tiratricol" (Press release). U.S. Food and Drug Administration. 21 November 2000. Archived from the original on 22 January 2001. Retrieved 8 August 2007.
  12. "Health Canada issues warning on products containing Tiratricol (TRIAC)" (Press release). Health Canada. 2 December 1999. Retrieved 8 August 2007.
Ball-and-stick model of the tiratricol molecule
Clinical data
Trade namesEmcitate
Other names3,3',5-triiodothyroacetic acid
TRIAC
AHFS/Drugs.comInternational Drug Names
Drug classThyroid hormone
ATC codeH03AA04 (WHO) D11AX08 (WHO)
Legal status
Legal statusEU: Rx-only[1][2]
Pharmacokinetic data
MetabolismLiver glucuronidation
ExcretionBile duct
Identifiers
IUPAC name
CAS Number51-24-1 X mark
PubChem CID5803
IUPHAR/BPS2637
DrugBankDB03604 check
ChemSpider5598 check
UNII29OQ9EU4R1
KEGGD07214 check
ChEBICHEBI:40021
ChEMBLChEMBL41632 check
CompTox Dashboard (EPA)DTXSID2045232 Edit this at Wikidata
ECHA InfoCard100.000.079 Edit this at Wikidata
Chemical and physical data
FormulaC14H9I3O4
Molar mass621.935 g·mol−1
3D model (JSmol)Interactive image
SMILES
InChI

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