Mechanism of activation of TPO receptor by some TPO nonpeptide mimetics. TPO nonpeptide mimetics such as eltrombopag activate the TPO receptor by a mechanism different from TPO (see “TPO nonpeptide mimetics”). Although drawn here to suggest direct binding of eltrombopag to the TM region of the TPO receptor, eltrombopag may bind elsewhere on the TPO receptor but may have its effect mediated by unique structures in the TM region. Most TPO nonpeptide mimetics do not compete for binding with rhTPO and have a biologic effect additive to that of rhTPO. Illustration by Paulette Dennis.