TC14012, a serum-stable derivative of T140, is a selective and peptidomimetic CXCR4 antagonist with an IC50 of 19.3 nM. TC14012 is a potent CXCR7 agonist with an EC50 of 350 nM for recruiting β-arrestin 2 to CXCR7. TC14012 has anti-HIV activity and anti-cancer activity[2].In Vitro: TC14012 (1 mM) inhibits more than 95% the infection of the CXCR4-expressing cells by the HXB2 (X4) or 89.6 (dual-tropic) strain whereas TC14012 (1 mM) does not inhibit all the infection of the CCR5-expressing cells by the SF162 (R5) or 89.6 (dualtropic) strain.
TC14012 leads to erk 1/2 phosphorylation in U373 cells, which express endogenous CXCR7 but not CXCR4. Upon stimulation with TC14012, CXCR7 and the CXCR7-Cter4 chimera are able to recruit arrestin, whereas CXCR4 and CXCR4-Cter7 remain silent[2].