CYP Enzyme

Direct IC50 (mM)a

Remogliflozinb

GSK279782b

GSK333081c

GSK1997711c

GSK1997714c

GSK355993c

1A2

>100

>100

>100

>300

>300

>300

2A6

>100

>100

NTd

NT

NT

NT

2B6

>100

>100

NT

NT

NT

NT

2C8

>100

>100

NT

NT

NT

NT

2C9

>100

>100

>100

>300

>300

>300

2C19

>100

>100

>100

>300

>300

>300

2D6

>100

>100

>100

>300

>300

>300

3A4

>100

>100

>100

>300

>300

>300

aDirection inhibition studies added the inhibitor with probe substrate together. Assays were initiated with addition of cofactor.
b
CYP HPLC-LC/MS Inhibition method with probes substrates: CYP 1A2 Phenacetin; 2A6 – Coumarin; 2B6 – Buproprion; 2C8 – Rosiglitazone; 2C9 – Diclofenac; 2C19 – Mephenytoin; 2D6 – Bufuraol; 3A4 – Atorvastatin, Midazolam, and Nifedipine
cCYP Flourescence Inhibition Method with probe substrates: CYP 1A2- ethoxyresorufin; 2C9 – 7-methoxy-4-trifluromethylcoumarin-3-acetic acid; 2C19 – 3-butyryl-7- methoxycoumarin; 2D6 – 4-methylaminomethyl-7-methoxycoumarin; 3A4 – diethoxyfluorescein and 7-benzyloxyquinoline
dNT = not tested
Table 3: Inhibition of Cytochrome P450 Enzymes by Remogliflozin etabonate, Remogliflozin and Metabolites.