Sobetirome

Sobetirome
Clinical data
Other names	GC-1
Routes of; administration	Oral
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name 2-[4-[(4-Hydroxy-3-propan-2-ylphenyl)methyl]-3,5-dimethylphenoxy]acetic acid;
CAS Number	211110-63-3;
PubChem CID	9862248;
IUPHAR/BPS	2639;
DrugBank	DB07425;
ChemSpider	8037944;
UNII	XQ31741E9Q;
KEGG	D09381;
ChEBI	CHEBI:79988;
ChEMBL	ChEMBL107400;
CompTox Dashboard (EPA)	DTXSID60891557 ;
Chemical and physical data
Formula	C20H24O4
Molar mass	328.408 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CC(=CC(=C1CC2=CC(=C(C=C2)O)C(C)C)C)OCC(=O)O;
	InChI InChI=1S/C20H24O4/c1-12(2)17-9-15(5-6-19(17)21)10-18-13(3)7-16(8-14(18)4)24-11-20(22)23/h5-9,12,21H,10-11H2,1-4H3,(H,22,23); Key:QNAZTOHXCZPOSA-UHFFFAOYSA-N;

Sobetirome (GC-1) is a thyromimetic drug that binds to the thyroid hormone receptor TRβ1 preferentially compared to TRα1. It has been investigated for the treatment of dyslipidemia, obesity,^[1] Pitt–Hopkins syndrome,^[2] cholestatic liver disease,^[3] multiple sclerosis,^[4] bleomycin-induced lung fibrosis,^[5] and COVID-19 caused ARDS.^[6] It was designated as an orphan drug by the FDA for the treatment of X-linked adrenoleukodystrophy.^[7]

References

^ Lammel Lindemann, Jan; Webb, Paul (2016). "Sobetirome: the past, present and questions about the future". Expert Opinion on Therapeutic Targets. 20 (2): 145–149. doi:10.1517/14728222.2016.1090429. ISSN 1744-7631. PMID 26565124.
^ Bohlen, Joseph F; Cleary, Colin M; Das, Debamitra; Sripathy, Srinidhi Rao; Sadowski, Norah; Shim, Gina; Kenney, Rakaia F; Buchler, Ingrid P; Banerji, Tapasree; Scanlan, Thomas S; Mulkey, Daniel K; Maher, Brady J (1 August 2023). "Promyelinating drugs promote functional recovery in an autism spectrum disorder mouse model of Pitt–Hopkins syndrome". Brain. 146 (8): 3331–3346. doi:10.1093/brain/awad057. PMC 10393406. PMID 37068912.
^ Kosar, Karis; Cornuet, Pamela; Singh, Sucha; Liu, Silvia; Nejak-Bowen, Kari (May 2020). "The Thyromimetic Sobetirome (GC-1) Alters Bile Acid Metabolism in a Mouse Model of Hepatic Cholestasis". The American Journal of Pathology. 190 (5): 1006–1017. doi:10.1016/j.ajpath.2020.01.015. ISSN 0002-9440. PMC 7221298. PMID 32205094.
^ Shah, Kamal; Chauhan, Durgesh Nandini; Chauhan, Nagendra Singh; Mishra, Pradeep (13 May 2020). Recent Advancement in Prodrugs. CRC Press. ISBN 978-1-000-05799-7.
^ Matralis, Alexios; Karampitsakos, Theodoros; Papaioannou, Ourania; Katsaras, Matthaios; Sampsonas, Fotios; Bouros, Demosthenes; Aidinis, Vassilis; Tzouvelekis, Argyrios (5 September 2021). "Biosynthesis and implementation of Thyroid Receptor beta (TRß) agonists (thyromimetics) for the treatment of pulmonary fibrosis". European Respiratory Journal. 58 (suppl 65): OA4334. doi:10.1183/13993003.congress-2021.OA4334. ISSN 0903-1936. S2CID 244680799.
^ Hartley, Pamela. "$100,000 Gift Speeds Exploration of Sobetirome as COVID-19 Treatment". medicine.yale.edu. Retrieved 15 September 2023.
^ "Search Orphan Drug Designations and Approvals". www.accessdata.fda.gov. Retrieved 15 September 2023.

[1] Lammel Lindemann, Jan; Webb, Paul (2016). "Sobetirome: the past, present and questions about the future". Expert Opinion on Therapeutic Targets. 20 (2): 145–149. doi:10.1517/14728222.2016.1090429. ISSN 1744-7631. PMID 26565124.

[2] Bohlen, Joseph F; Cleary, Colin M; Das, Debamitra; Sripathy, Srinidhi Rao; Sadowski, Norah; Shim, Gina; Kenney, Rakaia F; Buchler, Ingrid P; Banerji, Tapasree; Scanlan, Thomas S; Mulkey, Daniel K; Maher, Brady J (1 August 2023). "Promyelinating drugs promote functional recovery in an autism spectrum disorder mouse model of Pitt–Hopkins syndrome". Brain. 146 (8): 3331–3346. doi:10.1093/brain/awad057. PMC 10393406. PMID 37068912.

[3] Kosar, Karis; Cornuet, Pamela; Singh, Sucha; Liu, Silvia; Nejak-Bowen, Kari (May 2020). "The Thyromimetic Sobetirome (GC-1) Alters Bile Acid Metabolism in a Mouse Model of Hepatic Cholestasis". The American Journal of Pathology. 190 (5): 1006–1017. doi:10.1016/j.ajpath.2020.01.015. ISSN 0002-9440. PMC 7221298. PMID 32205094.

[4] Shah, Kamal; Chauhan, Durgesh Nandini; Chauhan, Nagendra Singh; Mishra, Pradeep (13 May 2020). Recent Advancement in Prodrugs. CRC Press. ISBN 978-1-000-05799-7.

[5] Matralis, Alexios; Karampitsakos, Theodoros; Papaioannou, Ourania; Katsaras, Matthaios; Sampsonas, Fotios; Bouros, Demosthenes; Aidinis, Vassilis; Tzouvelekis, Argyrios (5 September 2021). "Biosynthesis and implementation of Thyroid Receptor beta (TRß) agonists (thyromimetics) for the treatment of pulmonary fibrosis". European Respiratory Journal. 58 (suppl 65): OA4334. doi:10.1183/13993003.congress-2021.OA4334. ISSN 0903-1936. S2CID 244680799.

[6] Hartley, Pamela. "$100,000 Gift Speeds Exploration of Sobetirome as COVID-19 Treatment". medicine.yale.edu. Retrieved 15 September 2023.

[7] "Search Orphan Drug Designations and Approvals". www.accessdata.fda.gov. Retrieved 15 September 2023.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

Clinical data

Other names	GC-1
Routes of administration	Oral
Legal status
Legal status	Investigational
Identifiers
IUPAC name 2-[4-[(4-Hydroxy-3-propan-2-ylphenyl)methyl]-3,5-dimethylphenoxy]acetic acid
CAS Number	211110-63-3
PubChem CID	9862248
IUPHAR/BPS	2639
DrugBank	DB07425
ChemSpider	8037944
UNII	XQ31741E9Q
KEGG	D09381
ChEBI	CHEBI:79988
ChEMBL	ChEMBL107400
CompTox Dashboard (EPA)	DTXSID60891557
Chemical and physical data
Formula	C₂₀H₂₄O₄
Molar mass	328.408 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CC1=CC(=CC(=C1CC2=CC(=C(C=C2)O)C(C)C)C)OCC(=O)O
InChI InChI=1S/C20H24O4/c1-12(2)17-9-15(5-6-19(17)21)10-18-13(3)7-16(8-14(18)4)24-11-20(22)23/h5-9,12,21H,10-11H2,1-4H3,(H,22,23) Key:QNAZTOHXCZPOSA-UHFFFAOYSA-N