Submission Details
Molecule(s):
PET-UNK-10339a1d-1
Duplicate of:
ALP-POS-a9ad2217-2
CN(C(=O)[C@@H]1CC[C@H](C(=O)N2CCCC2)O1)C(C(=O)Nc1cncc2ccccc12)c1cccc(Cl)c1
Design Rationale:
MAT-POS-a13804f0-4 exhibits excellent potency (actually more potent than in enzyme inhibition assay) in the cell-based assay . Capping amide NH with methyl makes the molecular structure look less peptidic and has the potential to improve pharmacokinetic behavior. There are a number of explanations for the observation that MAT-POS-a13804f0-4 is more potent in the cell-based assay than in the enzyme inhibition assay (mutant enzyme in cell-based assay; active transport of inhibitor into cells).
Other Notes:
Following the MAT-POS-a13804f0-4 design, I've submitted the design with the configuration of one of the chiral centers unspecified. I have not included a PDB file with this submission because of the uncertainty in both binding mode and configuration of the unspecified chiral center.