BRINP2-related peptide

BRINP2-related peptide
Clinical data
Other names	BRINP2-related peptide; BRP
Routes of; administration	Subcutaneous, Intravenous, Intraperitoneal
Drug class	Peptide-based metabolic modulator
Legal status
Legal status	Investigational;
Pharmacokinetic data
Metabolism	Proteolytic degradation (Arg-Arg cleavage site)
Chemical and physical data
Formula	C68H117N25O14S
Molar mass	1540.91 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(N)=O;
	InChI InChI=1S/C68H117N25O14S/c1-10-37(8)53(93-57(99)43(21-16-24-81-68(76)77)85-62(104)48(29-40-31-78-33-82-40)90-64(106)52(70)38(9)94)65(107)91-46(27-36(6)7)58(100)84-41(19-14-22-79-66(72)73)55(97)83-42(20-15-23-80-67(74)75)56(98)86-44(25-34(2)3)59(101)88-47(28-39-17-12-11-13-18-39)61(103)89-49(30-51(69)95)63(105)87-45(26-35(4)5)60(102)92-50(32-108)54(71)96/h11-13,17-18,31,33-38,41-50,52-53,94,108H,10,14-16,19-30,32,70H2,1-9H3,(H2,69,95)(H2,71,96)(H,78,82)(H,83,97)(H,84,100)(H,85,104)(H,86,98)(H,87,105)(H,88,101)(H,89,103)(H,90,106)(H,91,107)(H,92,102)(H,93,99)(H4,72,73,79)(H4,74,75,80)(H4,76,77,81)/t37-,38+,41-,42-,43-,44-,45-,46-,47-,48-,49-,50-,52-,53-/m0/s1; Key:HMJIRJDBVYKLDC-KVBBLKIJSA-N;

BRINP2-related peptide (BRP) is a peptide developed at Stanford which displays anti-obesity action similar to semaglutide. It does this without significant muscle loss or anxiety and without impacting bowel movement when administered to mice and pigs.^[2] BRP primarily stimulates receptors in the hypothalamus and is consistent with GPCR activation leading to stimulation of CREB and Fos activity in neuronal cells.^[1]

BRP is a peptide derived from the BRINP2 protein, corresponding to amino acids 386–397 (THRILRRLFNLC) of BRINP2.^[1]^[3] This 12-amino acid peptide is flanked by KK and KR recognition sites within the BRINP2 protein, which are cleaved by proprotein convertases to release the peptide. BRP has been detected in human cerebrospinal fluid by mass spectrometry.^[1] Additionally, BRP undergoes C-terminal amidation, resulting in the sequence THRILRRLFNLC-NH₂. The non-amidated form of the peptide is inactive.^[1]

References

^ ^a ^b ^c ^d ^e Coassolo L, B Danneskiold-Samsøe N, Nguyen Q, Wiggenhorn A, Zhao M, Wang DC, et al. (March 2025). "Prohormone cleavage prediction uncovers a non-incretin anti-obesity peptide". Nature. 641 (8061): 192–201. Bibcode:2025Natur.641..192C. doi:10.1038/s41586-025-08683-y. PMC 12043402. PMID 40044869.
^ Conger K (5 March 2025). "Stanford scientists develop potential Ozempic alternative". Stanford Medicine News. Retrieved 8 March 2025.
^ WO 2024/030214, Svensson KJ, Voilquin L, "Brinp2-Derived Peptide Compositions for Treating Obesity and Weight Management", published 8 February 2024, assigned to The Board of Trustees of the Leland Stanford Junior University.

[Coassolo_2025-1] Coassolo L, B Danneskiold-Samsøe N, Nguyen Q, Wiggenhorn A, Zhao M, Wang DC, et al. (March 2025). "Prohormone cleavage prediction uncovers a non-incretin anti-obesity peptide". Nature. 641 (8061): 192–201. Bibcode:2025Natur.641..192C. doi:10.1038/s41586-025-08683-y. PMC 12043402. PMID 40044869.

[StanfordBRP-2] Conger K (5 March 2025). "Stanford scientists develop potential Ozempic alternative". Stanford Medicine News. Retrieved 8 March 2025.

[BRPPatent-3] WO 2024/030214, Svensson KJ, Voilquin L, "Brinp2-Derived Peptide Compositions for Treating Obesity and Weight Management", published 8 February 2024, assigned to The Board of Trustees of the Leland Stanford Junior University.

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