Therapeutic Targets Database
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Target Validation Information
TTD IDTTDC00230
Target NameGastrin-releasing peptide receptor    
Type of TargetClinical trial target    
Drug Potency against Target[N40,Pro1,Tyr4]BBIC50 = 0.06 nM[1]
[(N4-Bzdig)0]BB(7-14)IC50 = 0.08 nM[1]
[N40,Pro1,Tyr4,Nle 14]BBIC50 = 0.15 nM[1]
[(N4-Bzdig)0,Nle14]BB(7-14)IC50 = 0.6 nM[1]
Universal ligandIC50 = 0.72 nM[1]
[Tyr4]BombesinIC50 = 0.85 nM[1]
Ac-His-Trp-Ala-Val-Gly-His-Leu-Met-NH2IC50 = 1.8 nM[2]
Ac-His-Trp-Ala-Val-Ala-His-Leu-Met-NH2IC50 = 180 nM[2]
Ac-His-Trp-Ala-Val-D-Ala-His-Leu-Met-NH2IC50 = 3.2 nM[2]
(CH3)CCO-His-Trp-Ala-Val-Gly-His-Leu-Met-NH2IC50 = 4.1 nM[2]
JMV 1802Ki = 0.8 nM[3]
JMV 1535Ki = 1 nM[3]
JMV 1799Ki = 1.2 nM[3]
JMV 1719Ki = 11 nM[3]
JMV 1801Ki = 2 nM[3]
JMV 1803Ki = 2 nM[3]
JMV 1813Ki = 2 nM[3]
JMV 1693Ki = 53 nM[3]
(D)Phe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2Ki = 6.3 nM[3]
Action against Disease ModelRC-3095RC-3095 at 1 nM concentration effectively inhibited the bombesin-stimulated growth of CFPAC-1 cells in cultures. In the presence of 1 microM RC-3095 in the culture medi uM, the bombesin-induced growth of CFPAC-1 cells was totally suppressed.[4]
The Effect of Target Knockout, Knockdown or Genetic VariationsPharmacologic/receptor-knockout studies show involvement of these receptors in a n uMber of new processes/diseases. Neuromedin B/BB1-receptor is an important physiological regulator of pituitary-thyroid function; in mediating behavior, especially feas/anxiety; in mediating satiety through different cascades than gastrin-releasing peptide/BB2 receptors and for its autocrine t uMor-growth effects. Gastrin-releasing peptide/BB2-receptor plays important roles in mediating signals for pruritus, lung development/injury, small intestinal mucosal defense, and central nervous system processes such as learning/memory. The signaling mechanisms of its potent growth effects are being elucidated and their possible therapeutic targets identified. BB3-receptor knockout mice provided insights for their obesity/glucose intolerance and demonstrated that this receptor may be important in the lung response to injury, t uMor growth and gastrointestinal motility. Each receptor is frequently overexpressed in h uMan t uMors and has potent growth effects. This effect is being explored to develop new antit uMor treatments, such as bombesin-receptor ligands conjugated to cytotoxic agents.[5]
Ref 1J Med Chem. 2005 Jan 13;48(1):100-10.Potent bombesin-like peptides for GRP-receptor targeting of tumors with 99mTc: a preclinical study. To Reference
Ref 2J Med Chem. 1991 Jul;34(7):2102-7.Gastrin releasing peptide antagonists with improved potency and stability. To Reference
Ref 3J Med Chem. 2000 Jun 15;43(12):2356-61.Synthesis and biological evaluation of bombesin constrained analogues. To Reference
Ref 4Oncogene. 2005 Aug 4;24(33):5262-8.Lipid modification of GRN163, an N3'-->P5' thio-phosphoramidate oligonucleotide, enhances the potency of telomerase inhibition. To Reference
Ref 5Curr Opin Endocrinol Diabetes Obes. 2008 Feb;15(1):58-64.Bombesin-related peptides and their receptors: recent advances in their role in physiology and disease states. To Reference



 

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