Natural Product (NP) Details

General Information of the NP (ID: NP2215)
Name
Colistin
Synonyms
colistin; Polymyxin E; 1066-17-7; Colobreathe; Promixin; Colistin,(S); CHEMBL499783; SCHEMBL1979092; GTPL10794; Colistin sulfate, >19000 IU/mg; N-[(2S)-4-amino-1-[[(2S,3R)-1-[[(2S)-4-amino-1-oxo-1-[[(3S,6S,9S,12S,15R,18S,21S)-6,9,18-tris(2-aminoethyl)-3-[(1R)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]-5-methylheptanamide; AB01566924_01; 066C177; Q418946; SR-01000872582; SR-01000872582-1; N-[(1S)-3-amino-1-[[(1S,2R)-1-[[(1S)-3-amino-1-[[(3S,6S,9S,12S,15R,18S,21S)-6,9,18-tris(2-aminoethyl)-3-[(1R)-1-hydroxyethyl]-12,15-diisobutyl-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]carbamoyl]propyl]carbamoyl]-2-hydroxy-propyl]carbamoyl]propyl]-5-methyl-heptanamide; N-[(1S)-3-amino-1-{[(1S,2R)-1-{[(1S)-3-amino-1-{[(3S,6S,9S,12S,15R,18S,21S)-6,9,18-tris(2-aminoethyl)-3-[(1R)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptaazacyclotricosan-21-yl]carbamoyl}propyl]carbamoyl}-2-; N-[(1S)-3-amino-1-{[(1S,2R)-1-{[(1S)-3-amino-1-{[(3S,6S,9S,12S,15R,18S,21S)-6,9,18-tris(2-aminoethyl)-3-[(1R)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptaazacyclotricosan-21-yl]carbamoyl}propyl]carbamoyl}-2-hydroxypropyl]carbamoyl}propyl]-5-methylheptanamide
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Species Origin Bacillus polymyxa ...     Click to Show/Hide
Bacillus polymyxa
SuperKingdom: Bacteria
Phylum: Firmicutes
Class: Bacilli
Order: Bacillales
Family: Paenibacillaceae
Genus: Paenibacillus
Species: Bacillus polymyxa
Disease Glanders [ICD-11: 1B92] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -6.694
 
MDCK Permeability
 -5.206
 
PAMPA
 +++
 
HIA
 +++
 
Distribution
VDss
 -0.685
 
PPB
 -9.8%
 
BBB
 - - -
 
Metabolism
CYP1A2 inhibitor
 - - -
CYP1A2 substrate
 - - -
CYP2C19 inhibitor
 - - -
CYP2C19 substrate
 - - -
CYP2C9 inhibitor
 - - -
CYP2C9 substrate
 - - -
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 - - -
CYP3A4 substrate
 - - -
CYP2B6 inhibitor
 - - -
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 - - -
HLM Stability
 - - -
 
Excretion
CLplasma
 1.173
 
T1/2
 1.999
Toxicity
DILI
 - - -
 
Rat Oral Acute Toxicity
 - - -
 
FDAMDD
 +
 
Respiratory
 - - -
 
Human Hepatotoxicity
 ++
 
Ototoxicity
 +++
 
Drug-induced Nephrotoxicity
 +
 
Drug-induced Neurotoxicity
 +++
 
Hematotoxicity
 - -
 
Genotoxicity
 +++
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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Formula
C52H98N16O13
PubChem CID
5311054
Canonical SMILES
CCC(C)CCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC1=O)CCN)CC(C)C)CC(C)C)CCN)CCN)C(C)O
InChI
1S/C52H98N16O13/c1-9-29(6)11-10-12-40(71)59-32(13-19-53)47(76)68-42(31(8)70)52(81)64-35(16-22-56)44(73)63-37-18-24-58-51(80)41(30(7)69)67-48(77)36(17-23-57)61-43(72)33(14-20-54)62-49(78)38(25-27(2)3)66-50(79)39(26-28(4)5)65-45(74)34(15-21-55)60-46(37)75/h27-39,41-42,69-70H,9-26,53-57H2,1-8H3,(H,58,80)(H,59,71)(H,60,75)(H,61,72)(H,62,78)(H,63,73)(H,64,81)(H,65,74)(H,66,79)(H,67,77)(H,68,76)/t29?,30-,31-,32+,33+,34+,35+,36+,37+,38+,39-,41+,42+/m1/s1
InChIKey
YKQOSKADJPQZHB-QNPLFGSASA-N
CAS Number
CAS 1066-17-7
TTD Drug ID
D0K7NQ
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Eravacycline      Infectious gastroenteritis/colitis     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model Acinetobacter baumannii Microorganism model Acinetobacter baumannii
                    Experimental
                    Result(s)		 Eravacycline and colistin combination may be a potential therapeutic option for the treatment of CRAB related infections.
    β. A List of Drug(s) Whose Resistance can be Reversed by This NP
          Niclosamide      Cestodes infection     Click to Show/Hide the Molecular Data of This Drug
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation		 Increase Zeta potential
                    In-vitro Model Acinetobacter baumannii Microorganism model Acinetobacter baumannii
Klebsiella pneumoniae Microorganism model Klebsiella pneumoniae
                    Experimental
                    Result(s)		 Niclosamide has potentiated the effect of colistin against Col-S and Col-R A.
          N-acetylcysteine      Liver disease     Click to Show/Hide the Molecular Data of This Drug
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation		 Increase Biofilm susceptibility
                    In-vitro Model Acinetobacter baumannii Microorganism model Acinetobacter baumannii
                    Experimental
                    Result(s)		 N-acetylcysteine, at concentrations achievable by topical administration, was shown to revert the colistin-resistant phenotype in A. baumannii, and to exert a relevant activity against biofilms of colistin-susceptible and colistin-resistant A. baumannii strains.
Target and Pathway
Target(s) Bacterial Dihydropteroate synthetase (Bact folP)  Molecule Info  [5]
References
Reference 1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Reference 2 In vitro activity of eravacycline in combination with colistin against carbapenem-resistant A. baumannii isolates. J Antibiot (Tokyo). 2019 Aug;72(8):600-604.
Reference 3 Synergistic Activity of Niclosamide in Combination With Colistin Against Colistin-Susceptible and Colistin-Resistant Acinetobacter baumannii and Klebsiella pneumoniae. Front Cell Infect Microbiol. 2018 Oct 3;8:348.
Reference 4 In vitro synergism of colistin in combination with N-acetylcysteine against Acinetobacter baumannii grown in planktonic phase and in biofilms. J Antimicrob Chemother. 2018 Sep 1;73(9):2388-2395.
Reference 5 Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant gram-negative bacteria. Ann Pharmacother. 1999 Sep;33(9):960-7.
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