Target Information

Target General Information

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Target ID

T68887 (Former ID: TTDI01778)

Target Name

Bombesin receptor (BS)

Synonyms

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Gene Name

NMBR; GRPR; BRS3

Target Type

Clinical trial target

[1]

Disease

[+] 2 Target-related Diseases

Breast cancer [ICD-11: 2C60-2C6Y]

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

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.

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BioChemical Class

GPCR rhodopsin

UniProt ID

NMBR_HUMAN ; GRPR_HUMAN ; BRS3_HUMAN

Sequence

MPSKSLSNLSVTTGANESGSVPEGWERDFLPASDGTTTELVIRCVIPSLYLLIITVGLLG
NIMLVKIFITNSAMRSVPNIFISNLAAGDLLLLLTCVPVDASRYFFDEWMFGKVGCKLIP
VIQLTSVGVSVFTLTALSADRYRAIVNPMDMQTSGALLRTCVKAMGIWVVSVLLAVPEAV
FSEVARISSLDNSSFTACIPYPQTDELHPKIHSVLIFLVYFLIPLAIISIYYYHIAKTLI
KSAHNLPGEYNEHTKKQMETRKRLAKIVLVFVGCFIFCWFPNHILYMYRSFNYNEIDPSL
GHMIVTLVARVLSFGNSCVNPFALYLLSESFRRHFNSQLCCGRKSYQERGTSYLLSSSAV
RMTSLKSNAKNMVTNSVLLNGHSMKQEMAL

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Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 2 Clinical Trial Drugs

BAY-86-7548

Drug Info

Phase 1

Solid tumour/cancer

[2]

Demobesin

Drug Info

Phase 1

Breast cancer

[3]

Mode of Action

[+] 4 Modes of Action

Enhancer

[+] 1 Enhancer drugs

BAY-86-7548

Drug Info

[4]

Antagonist

[+] 7 Antagonist drugs

Demobesin

Drug Info

[1]

bantag-1

Drug Info

[6]

kuwanon H

Drug Info

[8]

ML-18

Drug Info

[10]

PD 165929

Drug Info

[1]

PD 168368

Drug Info

[12]

PD 176252

Drug Info

[12]

Agonist

[+] 13 Agonist drugs

bag-1

Drug Info

[5]

bombesin

Drug Info

[7]

MK-5046

Drug Info

[9]

neuromedin B

Drug Info

[11]

phenylacetyl-Ala,DTrp-phenthylamide

Drug Info

[13]

PMID12723954C21b

Drug Info

[14]

PMID20167483C22e

Drug Info

[15]

PMID24412111C9f

Drug Info

[16]

PMID24412111C9g

Drug Info

[16]

PMID24900283C8a

Drug Info

[17]

PMID25497965C17c

Drug Info

[18]

ranatensin

Drug Info

[19]

[3H]bag-2

Drug Info

[5]

Inhibitor

[+] 1 Inhibitor drugs

[(N4-Bzdig)0]BB(7-14)

Drug Info

[20]

Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 1 KEGG Pathways

Neuroactive ligand-receptor interaction

Reactome

[+] 2 Reactome Pathways

Peptide ligand-binding receptors

G alpha (q) signalling events

WikiPathways

[+] 2 WikiPathways

GPCRs, Class A Rhodopsin-like

Peptide GPCRs

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 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).

REF 2

ClinicalTrials.gov (NCT01205321) PET/CT Imaging for Radiation Dosimetry, Plasma Pharmacokinetics, Biodistribution, Safety and Tolerability and Diagnostic Performance of BAY86-7548 in Patients With Prostate Cancer and Healthy Volunteers. U.S. National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT00989105) Technetium Tc 99m Demobesin-4 for Imaging Procedures in Patients With Prostate Cancer. U.S. National Institutes of Health.

REF 4

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.

REF 5

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.

REF 6

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.

REF 7

Expression and characterization of cloned human bombesin receptors. Mol Pharmacol. 1995 Jan;47(1):10-20.

REF 8

Non-peptide bombesin receptor antagonists, kuwanon G and H, isolated from mulberry. Biochem Biophys Res Commun. 1995 Aug 15;213(2):594-9.

REF 9

Antiobesity effect of MK-5046, a novel bombesin receptor subtype-3 agonist. J Pharmacol Exp Ther. 2011 Feb;336(2):356-64.

REF 10

ML-18 is a non-peptide bombesin receptor subtype-3 antagonist which inhibits lung cancer growth. Peptides. 2015 Feb;64:55-61.

REF 11

Insights into bombesin receptors and ligands: Highlighting recent advances. Peptides. 2015 Oct;72:128-44.

REF 12

Characterization of putative GRP- and NMB-receptor antagonist's interaction with human receptors. Peptides. 2009 Aug;30(8):1473-86.

REF 13

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.

REF 14

Design of selective peptidomimetic agonists for the human orphan receptor BRS-3. J Med Chem. 2003 May 8;46(10):1918-30.

REF 15

Discovery of substituted biphenyl imidazoles as potent, bioavailable bombesin receptor subtype-3 agonists. Bioorg Med Chem Lett. 2010 Mar 15;20(6):1913-7.

REF 16

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.

REF 17

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.

REF 18

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.

REF 19

Pharmacology and cell biology of the bombesin receptor subtype 4 (BB4-R). Biochemistry. 1999 Jun 1;38(22):7307-20.

REF 20

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.

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