Liothyronine(T3)
From DrugPedia: A Wikipedia for Drug discovery
| Line 1: | Line 1: | ||
'''Liothyronine(T3)''' | '''Liothyronine(T3)''' | ||
| - | Pubchem(5920) | + | '''Pubchem(5920)''' |
A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3. | A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3. | ||
| - | KEGG Pathway(C02465) | + | '''KEGG Pathway(C02465)''' |
| - | Tyrosine metabolism | + | *Tyrosine metabolism |
| - | Neuroactive ligand-receptor interaction | + | *Neuroactive ligand-receptor interaction |
Autoimmune thyroid disease | Autoimmune thyroid disease | ||
| + | |||
Comment Thyroid hormone | Comment Thyroid hormone | ||
More active than T4 | More active than T4 | ||
| Line 97: | Line 98: | ||
|- | |- | ||
|} | |} | ||
| - | + | {| border="1;width:100%; height:200px;style=text-align:center" | |
| - | Organism | + | |+'''Table I:''' |
| - | rat LDLo oral 7500mg/kg (7500mg/kg) Roczniki Panstwowego Zakladu Higieny. Vol. 32, Pg. 197, 1981. | + | |- |
| - | + | ! style="background:brown; color:white" |Organism | |
| + | ! style="background:brown; color:white" |Test Type | ||
| + | ! style="background:brown; color:white" |Route | ||
| + | ! style="background:brown; color:white" |Reported Dose (Normalized Dose) | ||
| + | ! style="background:brown; color:white" |Effect | ||
| + | ! style="background:brown; color:white" |Source | ||
| + | |- | ||
| + | |rat | ||
| + | |LDLo | ||
| + | |oral | ||
| + | |7500mg/kg (7500mg/kg) | ||
| + | |Roczniki Panstwowego Zakladu Higieny. Vol. 32, Pg. 197, 1981. | ||
| + | |- | ||
| + | |} | ||
Reference1 | Reference1 | ||
Nature Chemical Biology 4, 548 - 556 (2008) | Nature Chemical Biology 4, 548 - 556 (2008) | ||
Revision as of 06:25, 24 October 2008
Liothyronine(T3)
Pubchem(5920)
A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3.
KEGG Pathway(C02465)
- Tyrosine metabolism
- Neuroactive ligand-receptor interaction
Autoimmune thyroid disease
Comment Thyroid hormone More active than T4
| MMDB ID | PDB ID | Reference |
|---|---|---|
| 10776 | 1BSX | Darimont BD, Wagner RL, Apriletti JW, Stallcup MR, Kushner PJ, Baxter JD, Fletterick RJ, Yamamoto KRStructure and specificity of nuclear receptor-coactivator interactionsGenes Dev. v12, p.3343-3356 |
| 28583 | 1SN5 | Eneqvist T, Lundberg E, Karlsson A, Huang S, Santos CR, Power DM, Sauer-Eriksson AEHigh resolution crystal structures of piscine transthyretin reveal different binding modes for triiodothyronine and thyroxineJ. Biol. Chem. v279, p.26411-26416 |
| 31718 | 1XZX | Sandler B, Webb P, Apriletti JW, Huber BR, Togashi M, Cunha Lima ST, Juric S, Nilsson S, Wagner R, Fletterick RJ, Baxter JDThyroxine-thyroid hormone receptor interactionsJ. Biol. Chem. v279, p.55801-55808 |
| 40533 | 2H6W | Nascimento AS, Dias SM, Nunes FM, Aparicio R, Ambrosio AL, Bleicher L, Figueira AC, Santos MA, de Oliveira Ne, Fischer H, Togashi M, Craievich AF, Garratt RC, Baxter JD, Webb P, Polikarpov IStructural rearrangements in the thyroid hormone receptor hinge domain and their putative role in the receptor functionJ. Mol. Biol. v360, p.586-598 |
| 40534 | 2H77 | Nascimento AS, Dias SM, Nunes FM, Aparicio R, Ambrosio AL, Bleicher L, Figueira AC, Santos MA, de Oliveira Ne, Fischer H, Togashi M, Craievich AF, Garratt RC, Baxter JD, Webb P, Polikarpov IStructural rearrangements in the thyroid hormone receptor hinge domain and their putative role in the receptor functionJ. Mol. Biol. v360, p.586-598 |
| 40535 | PDB ID: 2H79 | Nascimento AS, Dias SM, Nunes FM, Aparicio R, Ambrosio AL, Bleicher L, Figueira AC, Santos MA, de Oliveira Ne, Fischer H, Togashi M, Craievich AF, Garratt RC, Baxter JD, Webb P, Polikarpov IStructural rearrangements in the thyroid hormone receptor hinge domain and their putative role in the receptor functionJ. Mol. Biol. v360, p.586-598 |
| 59297 | 2PIV | Estebanez-Perpina E, Arnold LA, Nguyen P, Rodrigues ED, Mar E, Bateman R, Pallai P, Shokat KM, Baxter JD, Guy RK, Webb P, Fletterick RJA surface on the androgen receptor that allosterically regulates coactivator bindingProc. Natl. Acad. Sci. U. S. A. v104, p.16074-16079 |
| 59298 | 2PIW | Estebanez-Perpina E, Arnold LA, Nguyen P, Rodrigues ED, Mar E, Bateman R, Pallai P, Shokat KM, Baxter JD, Guy RK, Webb P, Fletterick RJA surface on the androgen receptor that allosterically regulates coactivator bindingProc. Natl. Acad. Sci. U. S. A. v104, p.16074-16079 |
| Physical Property | Value | Units | Temp (deg C) | Source |
|---|---|---|---|---|
| Melting Point | 236.5 dec | deg C | EXP | |
| log P (octanol-water) | 2.960 (none) | EST | ||
| Water Solubility | 3.96 | mg/L | 37 | EXP |
| Vapor Pressure | 3.90E-16 | mm Hg | 25 | EST |
| Henry's Law Constant | 3.41E-18 | atm-m3/mole | 25 | EST |
| Atmospheric OH Rate Constant | 4.82E-11 | cm3/molecule-sec | 25 | EST |
| Organism | Test Type | Route | Reported Dose (Normalized Dose) | Effect | Source |
|---|---|---|---|---|---|
| rat | LDLo | oral | 7500mg/kg (7500mg/kg) | Roczniki Panstwowego Zakladu Higieny. Vol. 32, Pg. 197, 1981. |
Reference1 Nature Chemical Biology 4, 548 - 556 (2008) Published online: 10 August 2008 | doi:10.1038/nchembio.106
Cytosporone B is an agonist for nuclear orphan receptor Nur77
Yanyan Zhan1,3, Xiping Du1,3, Hangzi Chen1, Jingjing Liu1, Bixing Zhao1, Danhong Huang1, Guideng Li1, Qingyan Xu1, Mingqing Zhang1, Bart C Weimer2, Dong Chen2, Zhe Cheng1, Lianru Zhang1, Qinxi Li1, Shaowei Li1, Zhonghui Zheng1, Siyang Song1, Yaojian Huang1, Zhiyun Ye1, Wenjin Su1, Sheng-Cai Lin1, Yuemao Shen1 & Qiao Wu1
Abstract
Nuclear orphan receptor Nur77 has important roles in many biological processes. However, a physiological ligand for Nur77 has not been identified. Here, we report that the octaketide cytosporone B (Csn-B) is a naturally occurring agonist for Nur77. Csn-B specifically binds to the ligand-binding domain of Nur77 and stimulates Nur77-dependent transactivational activity towards target genes including Nr4a1 (Nur77) itself, which contains multiple consensus response elements allowing positive autoregulation in a Csn-B–dependent manner. Csn-B also elevates blood glucose levels in fasting C57 mice, an effect that is accompanied by induction of multiple genes involved in gluconeogenesis. These biological effects were not observed in Nur77-null (Nr4a1-/-) mice, which indicates that Csn-B regulates gluconeogenesis through Nur77. Moreover, Csn-B induced apoptosis and retarded xenograft tumor growth by inducing Nur77 expression, translocating Nur77 to mitochondria to cause cytochrome c release. Thus, Csn-B may represent a promising therapeutic drug for cancers and hypoglycemia, and it may also be useful as a reagent to increase understanding of Nur77 biological function.
