Resmetirom
Resmetirom · MGL-3196 · 2-(3,5-dichloro-4-((5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yl)oxy)phenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carbonitrile · CS-2429 · VIA3196 · VIA-3196 · MGL-3196(Resmetirom) · Resmetirom(MGL-3196)
식별자 및 물리적 특성
| CAS No. | 920509-32-6 |
|---|---|
| 분자식 | C17H12Cl2N6O4 |
| 평균 분자량 | 435.2 g/mol |
| 단동위원소 질량 | 434.0297083 g/mol |
| SMILES | CC(C)c1cc(Oc2c(Cl)cc(-n3nc(C#N)c(=O)[nH]c3=O)cc2Cl)n[nH]c1=O |
| InChIKey | FDBYIYFVSAHJLY-UHFFFAOYSA-N |
| PubChem CID | 15981237 |
| ChEMBL | CHEMBL3261331 |
| EC No. | 187-988-8 |
| DTXSID | DTXSID601352610 |
화학 및 물리적 성질
| XLogP | 2.7 |
|---|---|
| 극성 표면적 | 136 |
| 수소 결합 공여자 수 | 2 |
| 수소 결합 수용자 수 | 7 |
| 회전 가능 결합 수 | 4 |
| 무거운 원자 수 | 29 |
| 형식 전하 | 0 |
| 복잡도 | 878 |
| 의약품 | Pharmaceuticals -> Listed in ZINC15 |
| Human Drugs | Breast FeedingLactationMilk, HumanFDA approved drugs -> Active ingredientEMA approved medicines: Human medicine |
| 밀도 | 1.65±0.1 g/cm3(Predicted) |
| 저장 조건 | Inert atmosphere,Store in freezer, under -20°C |
| 용해도 | DMSO:59.0(Max Conc. mg/mL)135.56(Max Conc. mM) |
| 물리적 상태 | 결정성 고체 |
| pKa(산도 계수) | 3.96±0.40(Predicted) |
| 색상 | Yellow to orange |
| InChI | InChI=1S/C17H12Cl2N6O4/c1-7(2)9-5-13(22-23-15(9)26)29-14-10(18)3-8(4-11(14)19)25-17(28)21-16(27)12(6-20)24-25/h3-5,7H,1-2H3,(H,23,26)(H,21,27,28) |
| InChIKey | FDBYIYFVSAHJLY-UHFFFAOYSA-N |
| SMILES | N1=C(C#N)C(=O)NC(=O)N1C1=CC(Cl)=C(OC2=NNC(=O)C(C(C)C)=C2)C(Cl)=C1 |
안전 및 규제
| Hepatotoxicity | Mild, transient serum aminotransferase elevations develop in a high proportion of patients receiving resmetirom, generally within the first 4 weeks of therapy. These elevations are typically mild, self-limited, and not associated with symptoms or jaundice. Furthermore, these early changes were usually followed by a decrease in serum enzymes which were often within normal range 3 to 6 months later. These improvements in liver related enzymes correlated to some extent with the decrease in hepatic fat and histologic evidence of steatohepatitis. After 52 weeks of treatment, liver biopsies demonstrated resolution of NASH in 26% to 30% of patients. Whether these changes are sustained or increase with further therapy is not known. Therapy does not result in weight loss, and the improvements in hepatic histology and fibrosis may be lost once therapy is discontinued. |
|---|---|
| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation |
| 신호 어 | Warning |
| 유해·위험 문구 | 암호 유해·위험 문구 위험 등급 범주 신호 어 그림 문자 P- 코드 H302 |
용도
개요
MGL-3196 is an agonist of thyroid hormone receptor β (TRβ; EC50s = 0.21 and 3.74 μM for TRβ and TRα, respectively). It also inhibits ether-a-go-go-related gene (ERG) potassium channels (IC50 = 30 μM). MGL-3196 is a liver-directed compound, with a liver to plasma ratio of 8:1 in mice with diet-induced obesity (DIO), which reduces the likelihood of adverse effects from systemic exposure. It does not affect the expression of α-myosin heavy chain (α-MHC) in a rat model of hypothyroidism, an effect mediated by TRα, indicating low potential for cardiac adverse effects. MGL-3196 lowers non-HDL cholesterol and liver triglycerides without affecting thyroid stimulating hormone (Tsh) levels in rat and rabbit models of hypercholesterolemia. It also lowers plasma glucose levels and improves insulin sensitivity in DIO mice. Formulations containing MGL-3196 are in clinical trials for the treatment of non-alcoholic steatohepatitis (NASH) and familial hypercholesterolemia.
용도
Resmetirom (MGL-3196) is a liver-directed, orally active, selective thyroid hormone receptor-beta agonist. It works by blocking the formation of fat in the liver and can be used to treat non-alcoholic steatohepatitis (NASH).