CJC-1295 With DAC

What Is CJC-1295 With DAC?

CJC-1295 With DAC is the long-acting form of CJC-1295: the same DPP-IV-resistant GHRH 1-29 analogue, tetra-substituted at positions 2, 8, 15, and 27, with a maleimido-propionyl-lysine appended at the C-terminus. That maleimide tether is the Drug Affinity Complex. After administration, the maleimide group covalently binds the free cysteine-34 thiol on circulating serum albumin, so the active GHRH analogue rides albumin's clearance curve and remains in circulation for 6 to 8 days instead of 30 minutes.

The consequence is sustained occupation of the GHRH receptor on pituitary somatotrophs across the entire interval. Teichman et al. (2006, JCEM) is the landmark human pharmacokinetic and pharmacodynamic paper: a single administration produced 2- to 10-fold GH elevation and 1.5- to 3-fold IGF-1 elevation that remained significant for 14 to 28 days in healthy adults. The shape of the GH curve, not just its duration, is the clinically important difference. Native GHRH and CJC-1295 No DAC produce discrete pulses; the DAC form produces continuously elevated GH and IGF-1 with small residual pulsatility on top. Because hepatic IGF-1 output and somatotroph signalling are tuned to pulse pattern, continuous exposure is associated with greater insulin resistance and receptor downregulation. The 2006 trial also reported rising GH binding protein at higher exposures, and an unexplained death at one site that investigators did not attribute to the drug contributed to a halt in clinical development. No sponsor has since advanced the compound into Phase 3.