Table 1.

DILIsym Input Parameters for the CGRP Compounds, Including Parameters Related to Mitochondrial Toxicity, ROS Generation, and Bile Acid Transporter Inhibition

Mechanism	Parameter	Unit	DILIsym Parameter Valuea
			Telcagepant—High	Telcagepant—Low	Rimegepant	Zavegepant	Atogepant	Ubrogepant
Mitochondrial dysfunction	Coefficient for ETC inhibition 1	µM	3470	3470	3470	1600	38 170	Not used
	Coefficient for ETC Inhibition 3	µM	1.89	Removed	1.89	2	0.1	4,217
	Max inhibitory effect for ETC inhibition 3	Dimensionless	0.45	Removed	0.45	1.5	0.2	0.4
	Uncoupler 1 effect Km	mM	No effect	No effect	No effect		No effect	15 300
	Uncoupler 1 effect Vmax	Dimensionless	No effect	No effect	No effect		No effect	22.5
	Uncoupler 1 effect Hill	Dimensionless	No effect	No effect	No effect		No effect	4.3
Oxidative stress	RNS/ROS production rate constant 1	ml/nmol/h	3.5 × 10−4	3.5 × 10−4	3.5 × 10−4	No ROS production	3.41 × 10−4	1.65 ×10−4
Bile acid transporter inhibitionb	BSEP inhibition constant	µM	19.0	19.0	27.2	341	144.2	No inhibition
	BSEP inhibition alpha value	Dimensionless	4.32	4.32	Competitive	1.368	0.64	No inhibition
	NTCP inhibition constant	µM	No inhibition	No inhibition	No inhibition	No inhibition	No inhibition	No inhibition
	MRP4 inhibition constant	µM	42.4	42.4	No inhibition	No inhibition	42	75.3

^aValues shown in the table for DILIsym input parameters should not be interpreted in isolation with respect to clinical implications, but rather, should be combined with exposure in DILIsym to produce simulations that have predictive and insightful value.

^bIC₅₀ values were used for transporters other than BSEP, where K_i was measured; alpha value of 5 assumed when IC₅₀ measured.