Zosurabalpin

Synonym(s): RG6006

Class: Antimicrobial peptide (macrocyclic peptide)

Spectrum of activity:	Gram-negative
Details of activity:	Active against carbapenem-resistant Acinetobacter baumannii; targets the LptB2FGC complex in the Gram-negative inner membrane blocking lipopolysaccharide transport
Propensity to select resistant mutants:	Yes, at 10^-7 to 10^-9 mutation frequency
Description:	Synthetic compound from the Tranzyme Pharma compound library (RO7075573) which was further modified to produce this second-generation antibiotic; >5-log reduction in neutropenic mouse thigh Acinetobacter baumannii infection model
Institute where first reported:	Roche Pharma Research and Early Development, Immunology, Infectious Disease and Ophthalmology, Roche Innovation Center Basel, F. Hoffmann-La Roche, Basel, Switzerland
Year first mentioned:	2024
Highest developmental phase:	Phase 1 (NCT05614895)
Development status:	Active (as of 2024)

Chemical structure(s):
Canonical SMILES:	CN1[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)NCC4=C(C=CC=C4SC5=NC=CC=C5CN[C@@H](CCCN)C(=O)N[C@@H](CCCCN)C1=O)C6=CC=C(C=C6)C(=O)O
Isomeric SMILES:	CN1[C@H](C(=O)NCC2=C(C=CC=C2SC3=C(CN[C@H](C(=O)N[C@H](C1=O)CCCCN)CCCN)C=CC=N3)C4=CC=C(C=C4)C(=O)O)CC5=CNC6=CC=CC=C65
InChI:	InChI=1S/C43H50N8O5S/c1-51-37(23-30-25-47-34-12-3-2-10-32(30)34)40(53)49-26-33-31(27-16-18-28(19-17-27)43(55)56)11-6-15-38(33)57-41-29(9-8-22-46-41)24-48-35(14-7-21-45)39(52)50-36(42(51)54)13-4-5-20-44/h2-3,6,8-12,15-19,22,25,35-37,47-48H,4-5,7,13-14,20-21,23-24,26,44-45H2,1H3,(H,49,53)(H,50,52)(H,55,56)/t35-,36-,37-/m0/s1
InChI Key:	NJFUXFYUHIHHOJ-FSEITFBQSA-N
Structure link:	https://pubchem.ncbi.nlm.nih.gov/compound/148636827

External links:
Guide to Pharmacology:	zosurabalpin
Main Source:	https://www.nature.com/articles/s41586-023-06873-0
Citation:	https://academic.oup.com/ofid/article/10/Supplement_2/ofad500.1749/7446954
Patent:	US2019321440A1