Murepavadin

Synonym(s): POL7080  |  RG 7929

Class: Lipopolysaccharide synthesis inhibitor (LptD inhibitor)

Spectrum of activity:	Gram-negative
Details of activity:	Hospital-acquired bacterial pneumonia/ ventilator-associated bacterial pneumonia (caused by Pseudomonas aeruginosa)
Propensity to select resistant mutants:	Yes 10-10
Description:	Failed in Phase 3 due to nephrotoxicity, developed for inhalation therapy
Institute where first reported:	Polyphor (Roche licensee), Switzerland
Year first mentioned:	2008
Highest developmental phase:	Phase 3 (NCT03582007)
Development status:	Inactive
Reason Dropped:	Latent nephrotoxicity; Polyphor continued preclinical development of inhalation formulation and been granted clinical trial in UK on 2020

Chemical structure(s):
Canonical SMILES:	CC[C@H](C)[C@H]1C(=O)N[C@@H](CCN)C(=O)N[C@@H](CCCN)C(=O)N[C@H](CCN)C(=O)N[C@@H](CCN)C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H](CCN)C(=O)N[C@@H](CCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N4CCC[C@@H]4C(=O)N5CCC[C@H]5C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC6=CNC7=C6C=CC=C7)C(=O)N1
Isomeric SMILES:	CC[C@H](C)[C@H]1C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N2CCC[C@@H]2C(=O)N3CCC[C@H]3C(=O)N[C@H](C(=O)N[C@H](C(=O)N1)CC4=CNC5=CC=CC=C54)[C@@H](C)O)CO)C)CCN)CCN)CC6=CNC7=CC=CC=C76)CCN)CCN)CCCN)CCN
InChI:	InChI=1S/C73H112N22O16/c1-5-38(2)58-70(108)88-52(24-30-79)65(103)83-47(17-10-25-74)62(100)85-49(21-27-76)63(101)86-51(23-29-78)66(104)89-53(33-41-35-80-45-15-8-6-13-43(41)45)67(105)87-50(22-28-77)64(102)84-48(20-26-75)61(99)82-39(3)60(98)91-55(37-96)72(110)95-32-12-19-57(95)73(111)94-31-11-18-56(94)69(107)93-59(40(4)97)71(109)90-54(68(106)92-58)34-42-36-81-46-16-9-7-14-44(42)46/h6-9,13-16,35-36,38-40,47-59,80-81,96-97H,5,10-12,17-34,37,74-79H2,1-4H3,(H,82,99)(H,83,103)(H,84,102)(H,85,100)(H,86,101)(H,87,105)(H,88,108)(H,89,104)(H,90,109)(H,91,98)(H,92,106)(H,93,107)/t38-,39-,40+,47-,48-,49+,50-,51-,52-,53-,54-,55-,56-,57+,58-,59-/m0/s1
InChI Key:	RIDRXGOBXZLKHZ-NZUANIILSA-N

External links:
Structure link:	https://pubchem.ncbi.nlm.nih.gov/compound/91824766
Guide to Pharmacology:	murepavadin
Main Source:	http://www.polyphor.com/products/pol7080
Citations:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125514/pdf/e00490-18.pdf http://www.researchgate.net/publication/267910502_Mechanism_of_Action_of_POL7080_a_Novel_Anti-Pseudomonal_Compound