CHIR-090
featured

We are open as normal during COVID-19 pandemic. Order online, same day shipping out from North Carolina, USA

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 526733

CAS#: 728865-23-4

Description: CHIR-090 is a very potent and selective LpxC inhibitor. CHIR-090 has excellent antibiotic activity against Pseudomonas aeruginosa and Escherichia coli. CHIR-090 is also a two-step slow, tight-binding inhibitor of E. coli LpxC with Ki = 4.0 nM, Ki* = 0.5 nM, k5 = 1.9 min-1, and k6 = 0.18 min-1. CHIR-090 at low nanomolar levels inhibits LpxC orthologues from diverse Gram-negative pathogens, including P. aeruginosa, Neisseria meningitidis, and Helicobacter pylori. In contrast, CHIR-090 is a relatively weak competitive and conventional inhibitor (lacking slow, tight-binding kinetics) of LpxC from Rhizobium leguminosarum (Ki = 340 nM), a Gram-negative plant endosymbiont that is resistant to this compound. CHIR-090 is an excellent lead for the further development of new antibiotics targeting the lipid A pathway.


Price and Availability

Size Price Shipping out time Quantity
10mg USD 150 Same day
25mg USD 250 Same day
50mg USD 450 Same day
100mg USD 750 Same day
200mg USD 1250 Same day
500mg USD 1850 Same day
1g USD 2950 2 Weeks
2g USD 4250 2 Weeks
5g USD 8950 2 Weeks
Inquire bulk and customized quantity

Pricing updated 2020-10-31. Prices are subject to change without notice.

CHIR-090, purity > 98%, is in stock. The same day shipping after order is received.


Chemical Structure

img

Theoretical Analysis

MedKoo Cat#: 526733
Name: CHIR-090
CAS#: 728865-23-4
Chemical Formula: C24H27N3O5
Exact Mass: 437.1951
Molecular Weight: 437.496
Elemental Analysis: C, 65.89; H, 6.22; N, 9.60; O, 18.28


Synonym: CHIR-090; CHIR 090; CHIR090.

IUPAC/Chemical Name: N-[(2S,3R)-3-hydroxy-1-(hydroxyamino)-1-oxobutan-2-yl]-4-[2-[4-(morpholin-4-ylmethyl)phenyl]ethynyl]benzamide

InChi Key: FQYBTYFKOHPWQT-VGSWGCGISA-N

InChi Code: InChI=1S/C24H27N3O5/c1-17(28)22(24(30)26-31)25-23(29)21-10-8-19(9-11-21)3-2-18-4-6-20(7-5-18)16-27-12-14-32-15-13-27/h4-11,17,22,28,31H,12-16H2,1H3,(H,25,29)(H,26,30)/t17-,22+/m1/s1

SMILES Code: O=C(N[C@@H]([C@H](O)C)C(NO)=O)C1=CC=C(C#CC2=CC=C(CN3CCOCC3)C=C2)C=C1


Technical Data

Appearance:
White to off-white solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Certificate of Analysis:

Safety Data Sheet (SDS):

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code:
2934.99.9001


References

1: Titecat M, Liang X, Lee CJ, Charlet A, Hocquet D, Lambert T, Pagès JM, Courcol R, Sebbane F, Toone EJ, Zhou P, Lemaitre N. High susceptibility of MDR and XDR Gram-negative pathogens to biphenyl-diacetylene-based difluoromethyl-allo-threonyl-hydroxamate LpxC inhibitors. J Antimicrob Chemother. 2016 Jun 20. pii: dkw210. [Epub ahead of print] PubMed PMID: 27330072.

2: Kalinin D, Holl R. Insights into the zinc-dependent deacetylase LpxC: biochemical properties and inhibitor design. Curr Top Med Chem. 2016 Apr 13. [Epub ahead of print] PubMed PMID: 27072691.

3: Vincent IM, Ehmann DE, Mills SD, Perros M, Barrett MP. Untargeted Metabolomics To Ascertain Antibiotic Modes of Action. Antimicrob Agents Chemother. 2016 Mar 25;60(4):2281-91. doi: 10.1128/AAC.02109-15. Print 2016 Apr. PubMed PMID: 26833150; PubMed Central PMCID: PMC4808186.

4: Yao J, Bruhn DF, Frank MW, Lee RE, Rock CO. Activation of Exogenous Fatty Acids to Acyl-Acyl Carrier Protein Cannot Bypass FabI Inhibition in Neisseria. J Biol Chem. 2016 Jan 1;291(1):171-81. doi: 10.1074/jbc.M115.699462. Epub 2015 Nov 13. PubMed PMID: 26567338; PubMed Central PMCID: PMC4697154.

5: Walkup GK, You Z, Ross PL, Allen EK, Daryaee F, Hale MR, O'Donnell J, Ehmann DE, Schuck VJ, Buurman ET, Choy AL, Hajec L, Murphy-Benenato K, Marone V, Patey SA, Grosser LA, Johnstone M, Walker SG, Tonge PJ, Fisher SL. Translating slow-binding inhibition kinetics into cellular and in vivo effects. Nat Chem Biol. 2015 Jun;11(6):416-23. doi: 10.1038/nchembio.1796. Epub 2015 Apr 20. PubMed PMID: 25894085; PubMed Central PMCID: PMC4536915.

6: Oddo A, Holl R. Design and stereoselective synthesis of a C-aryl furanoside as a conformationally constrained CHIR-090 analogue. Carbohydr Res. 2012 Oct 1;359:59-64. doi: 10.1016/j.carres.2012.06.006. Epub 2012 Jun 18. PubMed PMID: 22925765.

7: Caughlan RE, Jones AK, Delucia AM, Woods AL, Xie L, Ma B, Barnes SW, Walker JR, Sprague ER, Yang X, Dean CR. Mechanisms decreasing in vitro susceptibility to the LpxC inhibitor CHIR-090 in the gram-negative pathogen Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2012 Jan;56(1):17-27. doi: 10.1128/AAC.05417-11. Epub 2011 Oct 24. PubMed PMID: 22024823; PubMed Central PMCID: PMC3256010.

8: Mansoor UF, Vitharana D, Reddy PA, Daubaras DL, McNicholas P, Orth P, Black T, Siddiqui MA. Design and synthesis of potent Gram-negative specific LpxC inhibitors. Bioorg Med Chem Lett. 2011 Feb 15;21(4):1155-61. doi: 10.1016/j.bmcl.2010.12.111. Epub 2010 Dec 28. PubMed PMID: 21273067.

9: Cole KE, Gattis SG, Angell HD, Fierke CA, Christianson DW. Structure of the metal-dependent deacetylase LpxC from Yersinia enterocolitica complexed with the potent inhibitor CHIR-090 . Biochemistry. 2011 Jan 18;50(2):258-65. Epub 2010 Dec 20. PubMed PMID: 21171638; PubMed Central PMCID: PMC3070812.

10: Bodewits K, Raetz CR, Govan JR, Campopiano DJ. Antimicrobial activity of CHIR-090, an inhibitor of lipopolysaccharide biosynthesis, against the Burkholderia cepacia complex. Antimicrob Agents Chemother. 2010 Aug;54(8):3531-3. doi: 10.1128/AAC.01600-09. Epub 2010 Jun 1. PubMed PMID: 20516283; PubMed Central PMCID: PMC2916346.

11: Barb AW, Zhou P. Mechanism and inhibition of LpxC: an essential zinc-dependent deacetylase of bacterial lipid A synthesis. Curr Pharm Biotechnol. 2008 Feb;9(1):9-15. Review. PubMed PMID: 18289052; PubMed Central PMCID: PMC3022321.

12: Barb AW, Jiang L, Raetz CR, Zhou P. Structure of the deacetylase LpxC bound to the antibiotic CHIR-090: Time-dependent inhibition and specificity in ligand binding. Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18433-8. Epub 2007 Nov 19. Erratum in: Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):21020. PubMed PMID: 18025458; PubMed Central PMCID: PMC2141794.

13: Barb AW, McClerren AL, Snehelatha K, Reynolds CM, Zhou P, Raetz CR. Inhibition of lipid A biosynthesis as the primary mechanism of CHIR-090 antibiotic activity in Escherichia coli. Biochemistry. 2007 Mar 27;46(12):3793-802. Epub 2007 Mar 3. PubMed PMID: 17335290; PubMed Central PMCID: PMC2709454.

14: McClerren AL, Endsley S, Bowman JL, Andersen NH, Guan Z, Rudolph J, Raetz CR. A slow, tight-binding inhibitor of the zinc-dependent deacetylase LpxC of lipid A biosynthesis with antibiotic activity comparable to ciprofloxacin. Biochemistry. 2005 Dec 20;44(50):16574-83. PubMed PMID: 16342948; PubMed Central PMCID: PMC2742919.