Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTHYDUM)

• DTT Name: Bombesin receptor (BS)
• Synonyms: BB
• Gene Name: NMBR
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: NMBR_HUMAN ; GRPR_HUMAN ; BRS3_HUMAN
• TTD ID: T68887
• Sequence:
  MPSKSLSNLSVTTGANESGSVPEGWERDFLPASDGTTTELVIRCVIPSLYLLIITVGLLG
  NIMLVKIFITNSAMRSVPNIFISNLAAGDLLLLLTCVPVDASRYFFDEWMFGKVGCKLIP
  VIQLTSVGVSVFTLTALSADRYRAIVNPMDMQTSGALLRTCVKAMGIWVVSVLLAVPEAV
  FSEVARISSLDNSSFTACIPYPQTDELHPKIHSVLIFLVYFLIPLAIISIYYYHIAKTLI
  KSAHNLPGEYNEHTKKQMETRKRLAKIVLVFVGCFIFCWFPNHILYMYRSFNYNEIDPSL
  GHMIVTLVARVLSFGNSCVNPFALYLLSESFRRHFNSQLCCGRKSYQERGTSYLLSSSAV
  RMTSLKSNAKNMVTNSVLLNGHSMKQEMAL
• Function: Bombesin receptor activity. G protein-coupled receptor activity. Receptor for neuromedin-B. G protein-coupled receptor signaling pathway. Phospholipase C-activating G protein-coupled receptor signaling pathway.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BAY-86-7548	DM195JA	Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]
Demobesin	DMPXLMB	Breast cancer	2C60-2C65	Phase 1	[1]

20 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
bag-1	DMSWQED	Discovery agent	N.A.	Investigative	[3]
bantag-1	DM4OT8M	Discovery agent	N.A.	Investigative	[4]
bombesin	DMDFQ0Y	Discovery agent	N.A.	Investigative	[5]
kuwanon H	DMVQDNR	Discovery agent	N.A.	Investigative	[6]
MK-5046	DMS7C6R	Discovery agent	N.A.	Investigative	[7]
ML-18	DMHJCN6	Discovery agent	N.A.	Investigative	[8]
neuromedin B	DMCXJLH	Discovery agent	N.A.	Investigative	[9]
PD 165929	DM5J4NA	Discovery agent	N.A.	Investigative	[1]
PD 168368	DMFNQEA	Discovery agent	N.A.	Investigative	[10]
PD 176252	DM7AY6K	Discovery agent	N.A.	Investigative	[10]
phenylacetyl-Ala,DTrp-phenthylamide	DM5A8KR	Discovery agent	N.A.	Investigative	[11]
PMID12723954C21b	DM3EZ9Q	Discovery agent	N.A.	Investigative	[12]
PMID20167483C22e	DM8NGEQ	Discovery agent	N.A.	Investigative	[13]
PMID24412111C9f	DM6O7MK	Discovery agent	N.A.	Investigative	[14]
PMID24412111C9g	DM8JQL4	Discovery agent	N.A.	Investigative	[14]
PMID24900283C8a	DM6TYD0	Discovery agent	N.A.	Investigative	[15]
PMID25497965C17c	DMO6NEX	Discovery agent	N.A.	Investigative	[16]
ranatensin	DMI7NAF	Discovery agent	N.A.	Investigative	[17]
[(N4-Bzdig)0]BB(7-14)	DMD4BSJ	Discovery agent	N.A.	Investigative	[18]
[3H]bag-2	DMKL9X7	Discovery agent	N.A.	Investigative	[3]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 38).
• [2] Plasma pharmacokinetics, whole-body distribution, metabolism, and radiation dosimetry of 68Ga bombesin antagonist BAY 86-7548 in healthy men. J Nucl Med. 2013 Jun;54(6):867-72.
• [3] Regulation of energy homeostasis by bombesin receptor subtype-3: selective receptor agonists for the treatment of obesity. Cell Metab. 2010 Feb 3;11(2):101-12.
• [4] Comparative pharmacology of bombesin receptor subtype-3, nonpeptide agonist MK-5046, a universal peptide agonist, and peptide antagonist Bantag-1 for human bombesin receptors. J Pharmacol Exp Ther. 2013 Oct;347(1):100-16.
• [5] Expression and characterization of cloned human bombesin receptors. Mol Pharmacol. 1995 Jan;47(1):10-20.
• [6] Non-peptide bombesin receptor antagonists, kuwanon G and H, isolated from mulberry. Biochem Biophys Res Commun. 1995 Aug 15;213(2):594-9.
• [7] Antiobesity effect of MK-5046, a novel bombesin receptor subtype-3 agonist. J Pharmacol Exp Ther. 2011 Feb;336(2):356-64.
• [8] ML-18 is a non-peptide bombesin receptor subtype-3 antagonist which inhibits lung cancer growth. Peptides. 2015 Feb;64:55-61.
• [9] Insights into bombesin receptors and ligands: Highlighting recent advances. Peptides. 2015 Oct;72:128-44.
• [10] Characterization of putative GRP- and NMB-receptor antagonist's interaction with human receptors. Peptides. 2009 Aug;30(8):1473-86.
• [11] Pharmacology of putative selective hBRS-3 receptor agonists for human bombesin receptors (BnR): affinities, potencies and selectivity in multiple native and BnR transfected cells. Peptides. 2010 Aug;31(8):1569-78.
• [12] Design of selective peptidomimetic agonists for the human orphan receptor BRS-3. J Med Chem. 2003 May 8;46(10):1918-30.
• [13] Discovery of substituted biphenyl imidazoles as potent, bioavailable bombesin receptor subtype-3 agonists. Bioorg Med Chem Lett. 2010 Mar 15;20(6):1913-7.
• [14] Discovery of novel chiral diazepines as bombesin receptor subtype-3 (BRS-3) agonists with low brain penetration. Bioorg Med Chem Lett. 2014 Feb 1;24(3):750-5.
• [15] Discovery of benzodiazepine sulfonamide-based bombesin receptor subtype 3 agonists and their unusual chirality. ACS Med Chem Lett. 2011 Oct 3;2(12):933-7.
• [16] Synthesis and biological evaluation of novel chiral diazepine derivatives as bombesin receptor subtype-3 (BRS-3) agonists incorporating an antedrug approach. Bioorg Med Chem. 2015 Jan 1;23(1):89-104.
• [17] Pharmacology and cell biology of the bombesin receptor subtype 4 (BB4-R). Biochemistry. 1999 Jun 1;38(22):7307-20.
• [18] Potent bombesin-like peptides for GRP-receptor targeting of tumors with 99mTc: a preclinical study. J Med Chem. 2005 Jan 13;48(1):100-10.