Percentage of unchanged GDC-0834 and metabolites formed by incubation of 10 μM GDC-0834 in cryopreserved hepatocytes of the mouse, rat, dog, monkey, and human for 3 h
Percentage composition is semiquantitative and is based on peak areas of UV peaks and calculated relative to the parent compound (GDC-0834) at the 0-h time point.
| Analyte | Retention Time | M | R | D | C | H | Biotransformation Pathway |
|---|---|---|---|---|---|---|---|
| min | |||||||
| GDC-0834 | 22.6 | 44.1 | 79.5 | 83.1 | 46.5 | 19.9 | |
| M1 | 9.1 | 22.3 | 8.6 | 12.2 | 3.6 | 61.5 | Amide hydrolysis |
| M2 | 13.0 | 1.1 | 0.4 | 0.4 | 0.4 | 1.2 | Oxidation |
| M3 | 18.2 | 2.8 | 3.1 | 2.0 | 8.6 | 0.3 | N-Demethylation |
| M4 | 6.56 | 1.8 | N.D. | 1.2 | N.D. | N.D. | Amide hydrolysis + N-demethylation |
| M5 | 14.1 | 2.8 | 0.7 | 1.3 | 0.7 | 2.6 | Desaturation |
| M6 | 20.2 | 2.2 | N.D. | 4.3 | N.D. | N.D. | N-Demethylation |
| M7 | 20.3 | N.D. | N.D. | N.D. | 5.1 | N.D. | Oxidation |
| M8 | 21.2 | N.D. | 3.3 | N.D. | N.D. | N.D. | Oxidation |
M, mouse hepatocytes; R, rat hepatocytes; D, male beagle dog hepatocytes; C, male cynomolgus monkey hepatocytes; H, pooled human hepatocytes; N.D., not detected.