Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTC1MVT)

• DTT Name: Gastrin-releasing peptide receptor (GRPR)
• Synonyms: GRPR; GRP-preferring bombesin receptor; GRP-R; Bombesin/gastrin-releasing peptide receptor
• Gene Name: GRPR
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: GRPR_HUMAN
• TTD ID: T99816
• Sequence:
  MALNDCFLLNLEVDHFMHCNISSHSADLPVNDDWSHPGILYVIPAVYGVIILIGLIGNIT
  LIKIFCTVKSMRNVPNLFISSLALGDLLLLITCAPVDASRYLADRWLFGRIGCKLIPFIQ
  LTSVGVSVFTLTALSADRYKAIVRPMDIQASHALMKICLKAAFIWIISMLLAIPEAVFSD
  LHPFHEESTNQTFISCAPYPHSNELHPKIHSMASFLVFYVIPLSIISVYYYFIAKNLIQS
  AYNLPVEGNIHVKKQIESRKRLAKTVLVFVGLFAFCWLPNHVIYLYRSYHYSEVDTSMLH
  FVTSICARLLAFTNSCVNPFALYLLSKSFRKQFNTQLLCCQPGLIIRSHSTGRSTTCMTS
  LKSTNPSVATFSLINGNICHERYV
• Function: Receptor for gastrin-releasing peptide (GRP). Signals via association with G proteins that activate a phosphatidylinositol-calcium second messenger system, resulting in Akt phosphorylation. Contributes to the regulation of food intake. Contributes to the perception of prurient stimuli and transmission of itch signals in the spinal cord that promote scratching behavior, but does not play a role in the perception of pain. Contributes primarily to nonhistaminergic itch sensation. Contributes to long-term fear memory, but not normal spatial memory.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  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

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
177Lu-labelled NeoBOMB1	DM2TSMD	Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]
ASP-7147	DMGDF2X	Irritable bowel syndrome	DD91.0	Phase 2	[1]
RC-3095	DMIG98L	Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
177-Lu-NeoB	DM6JLNT	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[2]
177Lu-AMBA	DMFG1YA	Breast cancer	2C60-2C65	Phase 1	[4]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BIM-26226	DM9F4LP	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[5]

27 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(CH3)CCO-His-Trp-Ala-Val-Gly-His-Leu-Met-NH2	DMD0P4G	Discovery agent	N.A.	Investigative	[6]
(D)Phe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2	DMQN14X	Discovery agent	N.A.	Investigative	[7]
177Lu-labelled RM2	DMLC2VE	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
Ac-His-Trp-Ala-Val-Ala-His-Leu-Met-NH2	DMCA4QR	Discovery agent	N.A.	Investigative	[6]
Ac-His-Trp-Ala-Val-D-Ala-His-Leu-Met-NH2	DMUINVT	Discovery agent	N.A.	Investigative	[6]
Ac-His-Trp-Ala-Val-Gly-His-Leu-Met-NH2	DMUGO9M	Discovery agent	N.A.	Investigative	[6]
bantag-1	DM4OT8M	Discovery agent	N.A.	Investigative	[9]
bombesin	DMDFQ0Y	Discovery agent	N.A.	Investigative	[10]
JMV 1535	DMP1B9D	Discovery agent	N.A.	Investigative	[7]
JMV 1693	DMARTN3	Discovery agent	N.A.	Investigative	[7]
JMV 1719	DM82HW9	Discovery agent	N.A.	Investigative	[7]
JMV 1799	DMX3P68	Discovery agent	N.A.	Investigative	[7]
JMV 1801	DMTX694	Discovery agent	N.A.	Investigative	[7]
JMV 1802	DMGT6DN	Discovery agent	N.A.	Investigative	[7]
JMV 1803	DM248HC	Discovery agent	N.A.	Investigative	[7]
JMV 1813	DMSICYK	Discovery agent	N.A.	Investigative	[7]
kuwanon H	DMVQDNR	Discovery agent	N.A.	Investigative	[11]
MK-5046	DMS7C6R	Discovery agent	N.A.	Investigative	[9]
neuromedin B	DMCXJLH	Discovery agent	N.A.	Investigative	[10]
PD 168368	DMFNQEA	Discovery agent	N.A.	Investigative	[12]
PD 176252	DM7AY6K	Discovery agent	N.A.	Investigative	[13]
ranatensin	DMI7NAF	Discovery agent	N.A.	Investigative	[14]
[(N4-Bzdig)0,Nle14]BB(7-14)	DMVWCTL	Discovery agent	N.A.	Investigative	[15]
[(N4-Bzdig)0]BB(7-14)	DMD4BSJ	Discovery agent	N.A.	Investigative	[15]
[N40,Pro1,Tyr4,Nle 14]BB	DM6EAHF	Discovery agent	N.A.	Investigative	[15]
[N40,Pro1,Tyr4]BB	DMVFHNM	Discovery agent	N.A.	Investigative	[15]
[Tyr4]Bombesin	DMA6VNI	Discovery agent	N.A.	Investigative	[15]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Irritable bowel syndrome	DD91.0	Rectal colon tissue	9.39E-01	0.02	0.07
Breast cancer	2C82	Breast tissue	1.29E-01	-0.04	-0.08
Type 2 diabetes	5A11	Liver tissue	6.26E-01	-0.29	-0.6

References

• [1] Astellas and Drais Partner To Develop Third Astellas Compound through Tacurion
• [2] 68Ga/177Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in Oncology. J Nucl Med. 2017 Feb;58(2):293-299.
• [3] Lipid modification of GRN163, an N3'-->P5' thio-phosphoramidate oligonucleotide, enhances the potency of telomerase inhibition. Oncogene. 2005 Aug 4;24(33):5262-8.
• [4] Multimodality imaging and preclinical evaluation of 177Lu-AMBA for human prostate tumours in a murine model. Anticancer Res. 2010 Oct;30(10):4039-48.
• [5] Effect of the gastrin-releasing peptide antagonist BIM 26226 and lanreotide on an acinar pancreatic carcinoma. Eur J Pharmacol. 1998 Apr 17;347(1):77-86.
• [6] Gastrin releasing peptide antagonists with improved potency and stability. J Med Chem. 1991 Jul;34(7):2102-7.
• [7] Synthesis and biological evaluation of bombesin constrained analogues. J Med Chem. 2000 Jun 15;43(12):2356-61.
• [8] Radiopharmaceutical therapy in cancer: clinical advances and challenges. Nat Rev Drug Discov. 2020 Sep;19(9):589-608.
• [9] 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.
• [10] Expression and characterization of cloned human bombesin receptors. Mol Pharmacol. 1995 Jan;47(1):10-20.
• [11] Non-peptide bombesin receptor antagonists, kuwanon G and H, isolated from mulberry. Biochem Biophys Res Commun. 1995 Aug 15;213(2):594-9.
• [12] Comparative pharmacology of the nonpeptide neuromedin B receptor antagonist PD 168368. J Pharmacol Exp Ther. 1999 Sep;290(3):1202-11.
• [13] PD 176252--the first high affinity non-peptide gastrin-releasing peptide (BB2) receptor antagonist. Bioorg Med Chem Lett. 1998 Sep 22;8(18):2589-94.
• [14] Pharmacology and cell biology of the bombesin receptor subtype 4 (BB4-R). Biochemistry. 1999 Jun 1;38(22):7307-20.
• [15] 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.