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Endocrinol Metab : Endocrinology and Metabolism


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Michael D. Culler  (Culler MD) 1 Article
Endocrine Research
Therapeutic Effect of a Novel Chimeric Molecule Targeting Both Somatostatin and Dopamine Receptors on Growth Hormone-Secreting Pituitary Adenomas
Jean Kim, Ju Hun Oh, Heather Harlem, Michael D. Culler, Cheol Ryong Ku, Eun Jig Lee
Endocrinol Metab. 2020;35(1):177-187.   Published online March 19, 2020
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  • 4 Web of Science
  • 5 Crossref
AbstractAbstract PDFPubReader   ePub   

Acromegaly is a rare disease primarily caused by growth hormone (GH)-secreting pituitary adenomas, and its treatment is costly. Moreover, some patients are unresponsive to treatment. Hence, there are increasing efforts to develop new drugs with improved effectiveness for this disease. BIM23B065 is a novel chimeric molecule that acts on both somatostatin and dopamine receptors. This study aimed to investigate the effects of BIM23B065 compared with those of a somatostatin receptor analog and a dopamine agonist.


The effects of BIM23B065 on the proliferation, GH and insulin-like growth factor-1 (IGF-1) levels, and extracellular signal-regulated kinase (ERK) 1/2 and cyclic AMP response element binding (CREB) phosphorylation of GH3 cells were investigated with MTS assay, enzyme-linked immunosorbent assay, and Western blotting, respectively. The dosage and treatment duration of BIM23B065 were tested in animal models of GH-secreting pituitary adenoma. The effect of BIM23B065 (3 mg/kg/day) on changes in IGF-1 levels before and after treatment was further investigated.


In vitro, BIM23B065 treatment decreased GH release in the culture media and downregulated ERK 1/2 and CREB phosphorylation to 22% and 26%, respectively. In vivo, IGF-1 expression decreased to 50 % after 4 weeks of treatment with BIM23B065 using an osmotic pump implant. Moreover, magnetic resonance imaging results showed that the tumor size decreased significantly following treatment with BIM23B065 for 4 weeks.


The novel chimeric molecule was effective in decreasing IGF-1 and GH levels and may serve as an effective therapeutic agent for acromegaly.


Citations to this article as recorded by  
  • Pituitary Tumorigenesis—Implications for Management
    Rodanthi Vamvoukaki, Maria Chrysoulaki, Grigoria Betsi, Paraskevi Xekouki
    Medicina.2023; 59(4): 812.     CrossRef
  • Current and Emerging Medical Therapies in Pituitary Tumors
    Nicolas Sahakian, Frédéric Castinetti, Thierry Brue, Thomas Cuny
    Journal of Clinical Medicine.2022; 11(4): 955.     CrossRef
  • Characterization of the ability of a, second-generation SST-DA chimeric molecule, TBR-065, to suppress GH secretion from human GH-secreting adenoma cells
    Thomas Cuny, Thomas Graillon, Célines Defilles, Rakesh Datta, Shengwen Zhang, Dominique Figarella-Branger, Henry Dufour, Grégory Mougel, Thierry Brue, Tanya Landsman, Heather A. Halem, Michael D. Culler, Anne Barlier, Alexandru Saveanu
    Pituitary.2021; 24(3): 351.     CrossRef
  • Efficacy of a Novel Second-Generation Somatostatin-Dopamine Chimera (TBR-065) in Human Medullary Thyroid Cancer: A Preclinical Study
    Alessandra Dicitore, Maria Celeste Cantone, Germano Gaudenzi, Davide Saronni, Silvia Carra, Maria Orietta Borghi, Manuela Albertelli, Diego Ferone, Leo J. Hofland, Luca Persani, Giovanni Vitale
    Neuroendocrinology.2021; 111(10): 937.     CrossRef
  • Emerging drugs for the treatment of acromegaly
    Claudia Campana, Giuliana Corica, Federica Nista, Francesco Cocchiara, Giulia Graziani, Keyvan Khorrami, Marta Franco, Mara Boschetti, Diego Ferone, Federico Gatto
    Expert Opinion on Emerging Drugs.2020; 25(4): 409.     CrossRef
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