| Stereochemistry | ABSOLUTE |
| Molecular Formula | C16H14F3IN2O4 |
| Molecular Weight | 482.193 |
| Optical Activity | ( - ) |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OC[C@@H](O)CONC(=O)C1=C(NC2=C(F)C=C(I)C=C2)C(F)=C(F)C=C1
InChI
InChIKey=SUDAHWBOROXANE-SECBINFHSA-N
InChI=1S/C16H14F3IN2O4/c17-11-3-2-10(16(25)22-26-7-9(24)6-23)15(14(11)19)21-13-4-1-8(20)5-12(13)18/h1-5,9,21,23-24H,6-7H2,(H,22,25)/t9-/m1/s1
| Molecular Formula | C16H14F3IN2O4 |
| Molecular Weight | 482.193 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
PD-0325901 is an orally bioavailable inhibitor of mitogen-activated protein kinase kinases (MAPK/ERK kinases or MEK) with potential antineoplastic activity. MEK inhibitor PD325901, a derivative of MEK inhibitor CI-1040, selectively binds to and inhibits MEK, which may result in the inhibition of the phosphorylation and activation of MAPK/ERK and the inhibition of tumor cell proliferation. PD-0325901 is tested in clinical trials against non-small cell lung cancer, neurofibromatosis, melanoma and breast cancer.
Originator
Approval Year
Cmax
AUC
T1/2
Doses
AEs
PubMed
Sample Use Guides
In clinical trials against KRAS-mutant NSCLC PD-0325901 was administered orally twice daily, 3 weeks out of every 4 in each cycle. The initial dose for phase 1 of the study was be 2 mg twice daily.
Route of Administration:
Oral
MTT assay was used to evaluate effect of PD-0325901 on tumor cell proliferation. Briefly, cells (800/well) were seeded into a 96-well plate, and after 5 days of treatment with the indicated concentrations of PD0325901, 10 μL of 5 mg/mL MTT (Sigma) was added to cell culture, followed by addition of 100 μL of 10% sodium dodecyl sulfate (SDS) solution 4 hours later. After incubation for another 12 hours, the plates were read on a microplate reader at a test wavelength of 570 nm and a reference wavelength of 670 nm. PD-0325901 demonstrated potent inhibition of cells harboring BRAF or RAS mutations (KAK1, KAT5, KAT7, KAT10, NPA, DRO, and C643) with IC50 ranging from 0.059 to 0.783 uM.
