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Tubulin inhibitor payloads

aka auristatins, maytansinoids, microtubule payloads

Tubulin inhibitor payloads were the first generation of modern ADC payloads: drugs that jam the cell's scaffolding so it cannot divide. Nerve and eye side effects are typical.

Auristatins (MMAE, MMAF) and maytansinoids (DM1, DM4) bind tubulin and arrest mitosis, so they work best in rapidly dividing tumours. Whether the released form crosses membranes decides the bystander effect: MMAE and DM4 do, MMAF and DM1 do not. Peripheral neuropathy (MMAE), keratopathy (MMAF, DM4) and thrombocytopenia (DM1) are the characteristic toxicities. Most are substrates for P-glycoprotein.

Category
ADC chemistry

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