SPR741

SPR741
	Skeletal formula of SPR741
	peptide depiction (DAB = Diaminobutyric acid)
Clinical data
Other names	NAB741
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name (2S,3R)-2-acetamido-3-hydroxy-N-[(2R)-3-hydroxy-1-oxo-1-[[(3S,6S,9S,12S,15R,18S,21S)-6,9,18-tris(2-aminoethyl)-15-benzyl-3-[(1R)-1-hydroxyethyl]-12-(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]propan-2-yl]butanamide;
CAS Number	1179330-52-9;
PubChem CID	53323381;
IUPHAR/BPS	13250;
ChEMBL	ChEMBL1631770;
Chemical and physical data
Formula	C23H24N3O7P
Molar mass	485.433 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@H]([C@H]1C(=O)NCC[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)N1)CCN)CCN)CC(C)C)CC2=CC=CC=C2)CCN)NC(=O)[C@@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)C)O;
	InChI InChI=1S/C44H73N13O13/c1-22(2)19-31-40(66)52-27(11-15-45)36(62)51-29(13-17-47)39(65)57-34(23(3)59)43(69)48-18-14-30(53-42(68)33(21-58)56-44(70)35(24(4)60)49-25(5)61)38(64)50-28(12-16-46)37(63)55-32(41(67)54-31)20-26-9-7-6-8-10-26/h6-10,22-24,27-35,58-60H,11-21,45-47H2,1-5H3,(H,48,69)(H,49,61)(H,50,64)(H,51,62)(H,52,66)(H,53,68)(H,54,67)(H,55,63)(H,56,70)(H,57,65)/t23-,24-,27+,28+,29+,30+,31+,32-,33-,34+,35+/m1/s1; Key:JBFNEVNUGGFPBQ-DDMCRLCFSA-N;

SPR741 is an experimental antibiotic related to Polymyxin B. It shows activity against a number of bacterial pathogens, especially Acinetobacter baumannii and Klebsiella pneumoniae, acting as an antibiotic adjuvant which disrupts the outer membrane of Gram-negative bacteria and allows other antibiotics to more effectively penetrate into the cell.^[1]^[2]^[3]^[4]

References

^ Eckburg PB, Lister T, Walpole S, Keutzer T, Utley L, Tomayko J, et al. (September 2019). "Safety, Tolerability, Pharmacokinetics, and Drug Interaction Potential of SPR741, an Intravenous Potentiator, after Single and Multiple Ascending Doses and When Combined with β-Lactam Antibiotics in Healthy Subjects". Antimicrobial Agents and Chemotherapy. 63 (9). doi:10.1128/AAC.00892-19. PMC 6709486. PMID 31262767.
^ Vaara M (January 2019). "Polymyxin Derivatives that Sensitize Gram-Negative Bacteria to Other Antibiotics". Molecules. 24 (2): 249. doi:10.3390/molecules24020249. PMC 6359160. PMID 30641878.
^ She P, Liu Y, Xu L, Li Y, Li Z, Liu S, et al. (2022). "SPR741, Double- or Triple-Combined With Erythromycin and Clarithromycin, Combats Drug-Resistant Klebsiella pneumoniae, Its Biofilms, and Persister Cells". Frontiers in Cellular and Infection Microbiology. 12: 858606. doi:10.3389/fcimb.2022.858606. PMC 8971605. PMID 35372124.
^ Li Z, She P, Liu Y, Xu L, Li Y, Liu S, et al. (January 2023). "Triple combination of SPR741, clarithromycin, and erythromycin against Acinetobacter baumannii and its tolerant phenotype". Journal of Applied Microbiology. 134 (1). doi:10.1093/jambio/lxac023. PMID 36626755.

[1] Eckburg PB, Lister T, Walpole S, Keutzer T, Utley L, Tomayko J, et al. (September 2019). "Safety, Tolerability, Pharmacokinetics, and Drug Interaction Potential of SPR741, an Intravenous Potentiator, after Single and Multiple Ascending Doses and When Combined with β-Lactam Antibiotics in Healthy Subjects". Antimicrobial Agents and Chemotherapy. 63 (9). doi:10.1128/AAC.00892-19. PMC 6709486. PMID 31262767.

[2] Vaara M (January 2019). "Polymyxin Derivatives that Sensitize Gram-Negative Bacteria to Other Antibiotics". Molecules. 24 (2): 249. doi:10.3390/molecules24020249. PMC 6359160. PMID 30641878.

[3] She P, Liu Y, Xu L, Li Y, Li Z, Liu S, et al. (2022). "SPR741, Double- or Triple-Combined With Erythromycin and Clarithromycin, Combats Drug-Resistant Klebsiella pneumoniae, Its Biofilms, and Persister Cells". Frontiers in Cellular and Infection Microbiology. 12: 858606. doi:10.3389/fcimb.2022.858606. PMC 8971605. PMID 35372124.

[4] Li Z, She P, Liu Y, Xu L, Li Y, Liu S, et al. (January 2023). "Triple combination of SPR741, clarithromycin, and erythromycin against Acinetobacter baumannii and its tolerant phenotype". Journal of Applied Microbiology. 134 (1). doi:10.1093/jambio/lxac023. PMID 36626755.

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