Prolanta Structure

Prolanta™ (referenced in the scientific literature as G129R) is a prolactin receptor antagonist with a single amino acid mutation.

Human prolactin binds with its cell surface receptor (the prolactin receptor) through dimerization (or binding two receptors simultaneously), activating various pathways that stimulate cancer cell proliferation as well as resistance to chemotherapy. To counter the effect of human prolactin, we have developed an analogue protein (Prolanta™) with a single mutation at position 129, substituting an arginine amino acid for the existing glycine (thus the name G129R). This mutation allows Prolanta™ to bind to one prolactin receptor but not the second receptor. Thus, this binding interferes with the binding of normal prolactin.

Prolanta Structure

Our founding scientists demonstrated that a single amino acid substitution mutation at position 129 of the human prolactin resulted in a receptor-specific antagonist (Chen, Ramamoorthy et al. 1999; Beck, Peirce et al. 2002; Chen, Holle et al. 2002). The glycine to arginine substitution prevents the binding of this mutated ligand at the second prolactin receptor site, thereby disrupting dimerization of the receptors necessary for activation. In addition, our collaborators at MD Anderson Cancer Center have determined that Prolanta™ induces autophagy (cell death) in ovarian cancer cells (Wen, Zand et al. 2014).

The active ingredient of Prolanta™, the G129R protein, is produced in an E. coli expression system under cGMP conditions. The original expression system was licensed from Monsanto and has been fully characterized and the data was submitted to FDA in the IND. Prolanta is stored at 2-8°C in a lyophilized form and reconstituted with sterile water-for-injection immediately prior to use. Studies indicate that the drug produced under current methods should be stable for longer than one year. The contract manufacturer for Prolanta is BioVectra Inc., Prince Edward Island, Canada (USA FDA Registration No. 3004063541).


Beck, M. T., S. K. Peirce, et al. (2002). “Regulation of bcl-2 gene expression in human breast cancer cells by prolactin and its antagonist, hPRL-G129R.” Oncogene 21(33): 5047-55.

Chen, N. Y., L. Holle, et al. (2002). “In vivo studies of the anti-tumor effects of a human prolactin antagonist, hPRL-G129R.” Int J Oncol 20(4): 813-8.

Chen, W. Y., P. Ramamoorthy, et al. (1999). “A human prolactin antagonist, hPRL-G129R, inhibits breast cancer cell proliferation through induction of apoptosis.” Clin Cancer Res 5(11): 3583-93.

Wen, Y., B. Zand, B. Ozpolat, M.J. Szczepanski, C. Lu, E. Yuca, A.R. Carroll, N. Alpay, C. Bartholomeusz, I. Tekedereli, Y. Kang, R. Rupaimoole, C.V. Pecot, H.J. Dalton, A. Hernandez, A. Lokshin, S.K. Lutgendorf, J. Liu, W.N. Hittelman, W.Y. Chen, G. Lopez-Berestein, M. Szajnik, N.T. Ueno, R.L. Coleman, and A.K. Sood. (2014) Antagonism of tumoral prolactin receptor promotes autophagy-related cell death. Cell Rep 7(2): p. 488-500.