| Stereochemistry | RACEMIC |
| Molecular Formula | C12H9FN2O2 |
| Molecular Weight | 232.2105 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
FC1=CC2=C(NC=C2C3CC(=O)NC3=O)C=C1
InChI
InChIKey=MXKLDYKORJEOPR-UHFFFAOYSA-N
InChI=1S/C12H9FN2O2/c13-6-1-2-10-7(3-6)9(5-14-10)8-4-11(16)15-12(8)17/h1-3,5,8,14H,4H2,(H,15,16,17)
| Molecular Formula | C12H9FN2O2 |
| Molecular Weight | 232.2105 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | RACEMIC |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Optical Activity | ( + / - ) |
PF-06840003 is a highly selective orally bioavailable Indoleamine 2,3-dioxygenase-1 (IDO-1) inhibitor with a potent antineoplastic activity. PF-06840003 reversed IDO-1-induced T-cell anergy in vitro. In vivo, PF-06840003 reduced intratumoral kynurenine levels in mice by >80% and inhibited tumor growth in multiple preclinical syngeneic models in mice, in combination with immune checkpoint inhibitors. A Phase 1 study of PF-06840003 in patients with Malignant Gliomas is ongoing.
CNS Activity
Originator
Approval Year
Cmax
AUC
T1/2
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
Drug as victim
Tox targets
Sourcing
Patents
Sample Use Guides
The assay was performed in 96-well flat bottom plates seeded with P815 cells overexpressing hlDO1 at a concentration of 2 χ 10^5 cells/well in a final volume of 200 μΙ. To determine IDO1 activity, the cells were incubated 24 hours at 37 °C at 5% C02 in IMDM (Invitrogen) supplemented with 2% FBS and 2% penicillin/streptomycin in the presence of the compounds (Compound 1, PF-06840003) of the present invention, at different concentrations. The plates were then centrifuged 5 min at 1000 rpm, and 100 μΙ of the supernatant were collected in a conical plate, 30 uL of TCA 30% were added and a further centrifugated at 3000 x g for 1 0 minutes. 100 μΙ of the supernatant were collected in a flat bottomed plate and 1 00 μΙ of 2% (w/v) 4-(dimethylamino)-benzaldehyde in acetic acid and incubated for 5 min at room temperature. Kynurenine concentrations were determined by measuring the absorbance at 480 nm.
