Parameter | Value | Method/Reference |
---|---|---|
Molecular weight (g/mol) | 435.88 | CAS ID: 366789-02-8 |
Log P | 1.5 | Mueck et al., 2014 |
Compound type | Neutral | |
B/P | 0.71 | Grillo et al. 2012 |
fu | 0.065 | Grillo et al., 2012 |
Main plasma binding protein | Human serum albumin | (US Food and Drug Administration, 2011a)— |
Absorption model | ADAM model | |
fu,gut | 0.21 | Predicted |
Peff,man (10−4 cm/s) | 3.020492 | Predicted |
Permeability assay | Caco-2 | Gnoth et al., 2011 |
Apical pH: Basolateral pH | 7.4: 7.4 | Gnoth et al., 2011 |
Activity | Passive and active | Gnoth et al., 2011 |
Papp,A:B (10−6 cm/s) | 8 | Gnoth et al., 2011 |
Reference compound | Multiple | Gnoth et al., 2011 |
Reference compound Papp,A:B (10−6 cm/s) | 0 | Gnoth et al., 2011 |
Scalar | 1.284077 | Predicted |
Solubility pH Type | Intrinsic | |
Solubility (mg/ml) | 0.01 | Takács-Novák et al., 2013 |
Transporter | ABCB1 (P-gp/MDR1) | |
Jmax (pmol/min) | 37.83 | Determined experimentally |
Km (μM) | 9.416 | Determined experimentally |
fu,inc | 1 | Predicted |
Insert growth area of the Transwell (cm2) | 0.33 | Determined experimentally |
System | MDCK | Determined experimentally |
RAF/REF | 1.5 | |
Distribution model | Full PBPK model | |
VSS (l/kg) | 0.3824139 | Predicted: method 2 |
Enzyme | CYP3A4 | Predicted in Simcyp using the Retrograde Calculator |
Pathway | Pathway 1 | |
CLint (μl/min per picomoles) | 0.06353705 | |
Enzyme | CYP2J2 | Predicted in Simcyp using the Retrograde Calculator |
Pathway | Pathway 1 | |
CLint (μl/min per picomoles) | 5.685421 | |
CLint (HLM) (μl/min per milligram protein) | 7.998799 | Predicted in Simcyp using the Retrograde Calculator |
Mechanistic kidney model | ||
CLPD,basal (ml/min per million proximal tubular cells) | 1.09E−05 | Determined experimentally |
CLPD,apical (ml/min per million proximal tubular cells) | 1.09E−05 | Determined experimentally |
fu,kidney,cell | 0.3788975 | Predicted in Simcyp |
fu,urine | 1 | |
Transporter | SLC22A8 (OAT3) | |
Function | Uptake | |
CLint,T (μl/min per million cells) | 43 | Scaled using sensitivity analysis |
Transporter | ABCB1 (P-gp/MDR1) | |
Function | Efflux | |
Jmax (pmol/min per million cells) | 80.921 | Determined experimentally |
Km (μM) | 9.416 | Determined experimentally |
RAF/REF | 4 |
ADAM, advanced dissolution, absorption, and metabolism; B/P, blood to plasma partition ratio; CAS, Chemical Abstracts Service; CLint, in vitro intrinsic clearance; CLint,T, in vitro transporter-mediated intrinsic clearance; fu, fraction unbound in plasma; fu,gut, fraction unbound in the enterocytes; fu,inc, fraction unbound in the in vitro incubation; fu,urine, fraction unbound in the urine; fu,kidney,cell, fraction unbound in the kidney cell; HLM, human liver microsomes; ID, identification; log P, common logarithm of the octanol:water partition coefficient; Papp,A:B, apical-basolateral in vitro apparent permeability; Peff,man, human jejunum effective permeability; RAF/REF, relative activity factor/relative expression factor; Vss, volume of distribution at steady state.