| Stereochemistry | ACHIRAL |
| Molecular Formula | C17H12Cl2N6O4 |
| Molecular Weight | 435.221 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)C1=CC(OC2=C(Cl)C=C(C=C2Cl)N3N=C(C#N)C(=O)NC3=O)=NNC1=O
InChI
InChIKey=FDBYIYFVSAHJLY-UHFFFAOYSA-N
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)
| Molecular Formula | C17H12Cl2N6O4 |
| Molecular Weight | 435.221 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
MGL-3196 is a first-in-class, orally administered, small-molecule, liver-directed, THR β-selective agonist. Preclinical, toxicology and Phase 1 clinical data suggest MGL-3196 has an attractive, differentiated profile as a potential treatment for non-alcoholic steatohepatitis (NASH) and dyslipidemias. THR-β selectivity also enhances the safety profile of MGL-3196, compared to non-selective agents. MGL-3196 has shown no suppression of the central thyroid axis, no THR-α effects on heart rate or bone, and no elevation of liver enzymes. These characteristics make MGL-3196 among the most promising molecules in development in this therapeutic area. MGL-3196 is in a Phase 2 clinical trial for the treatment of non-alcoholic steatohepatitis (NASH).
CNS Activity
Originator
Approval Year
Doses
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
Drug as victim
Tox targets
Sourcing
Sample Use Guides
A two-week multiple dose study was conducted at doses of 5, 20, 50, 80, 100, and 200 mg per day in healthy subjects with mildly elevated low density lipoprotein (LDL) cholesterol. MGL-3196 was well-tolerated at all doses with no dose-related adverse events or liver enzyme, ECG or vital-sign changes. Doses ranging from 50 to 200 mg demonstrated highly statistically significant reductions relative to placebo of up to: 30% for LDL cholesterol (range, p = 0.05-<0.0001); 28% for non- high density lipoprotein (HDL) cholesterol (range, p = 0.027-0.0001); 24% for Apolipoprotein B (range, p = 0.008-0.0004), and statistical trends of up to 60% reduction in triglycerides (TG) (range, p = 0.13-0.016).
Route of Administration:
Oral
MGL-3196 is 28-fold selective for THR-β (EC50=0.21 uM) over THR-α (EC50=3.74 uM ) in a functional assay. MGL-3196 shows an IC20 of roughly 30 uM for blockage of the hERG channel. The IC50 for CYP3A4/5 and for CYP2C19 is >50 uM, and there is only weak inhibition (roughly 22 uM) of CYP2C9.
