PF-06380101 is an auristatin microtubule inhibitor and is a cytotoxic Dolastatin 10 analogue. When compared to other synthetic auristatin analogues that are used in the preparation of ADCs, PF-06380101 displays excellent potencies in tumor cell proliferation assays and differential ADME properties.

PF-06380101 is anticipated to be of low risk to perpetrate pharmacokinetic drug interactions with compounds for which CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and/or CYP3A4/5-mediated metabolism constitutes the primary mechanism of clearance. PF-06380101 preferentially distributes into human plasma relative to whole blood and that PF-06380101 is a P-glycoprotein (P-gp) substrate. PF-06380101 exhibited a mean systemic clearance (Cl) of 70 mL/min/kg and a volume of distribution (Vss) of 14.70 L/kg after an IV dose of 20a at 20 μg/kg to Wistar Han rats, resulting in a terminal elimination half-life (t1/2) of approximately 6 h. The utility of the new auristatin analogues as ADC payloads including the development of the lead analogue 20a (PF-06380101) will be reported in due course.