Current Status Of Peptide Agonists For Cytokine Receptors

Many recombinant cytokines are successfully marketed as drugs, including recombinant forms of human growth hormone (hGH), EPO, G-CSF, interferon (IFN)-a, IFN-P, interleukin (IL)-2, and IL-11 (44). Others are in late stages of clinical development. Scientists have been searching for smaller peptide cytokine agonists that mimic the activity of their larger counterparts to use as probes for understanding the detailed mechanisms of receptor activation. EPO mimetic peptide 1 (EMP1) was the first reported peptidomimetic (45). Subsequently, small-peptide agonists of the EPO and TPO receptors, including the EMP1-related peptides AF13948 (46), PK1 (47), and GW395058 (48), were reported.

SB 247464 W /

Fig. 4. Small-molecule hematopoietic growth factor agonists and antagonists. (A) G-CSFR agonist, SB 247464. (B) TPOR agonist, TM41. (C) EPOR antagonist, biphenyl indole. (D) TPOR agonist, SB 394725. (E) TPOR agonist, salicylaldehyde thiosemicarbazone. (F) TPOR agonist, naphtho[1,2-d]imidazole.

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