ZOLIFLODACIN


Synonyms	AZD-0914 AZD0914 ETX-0914 ETX0914 Zoliflodacin
Status
Molecule Category	UNKNOWN
UNII	FWL2263R77


Active Pharmaceutical Ingredients Bioactive chemicals	Exact Similarity SubStructure	Threshold (%) >= 70

Structure


InChI Key	ZSWMIFNWDQEXDT-ZESJGQACSA-N
Smiles	C[C@@H]1CN2c3c(cc4c(N5C(=O)OC[C@@H]5C)noc4c3F)CC3(C(=O)NC(=O)NC3=O)[C@H]2[C@H](C)O1
InChI	InChI=1S/C22H22FN5O7/c1-8-7-33-21(32)28(8)17-12-4-11-5-22(18(29)24-20(31)25-19(22)30)16-10(3)34-9(2)6-27(16)14(11)13(23)15(12)35-26-17/h4,8-10,16H,5-7H2,1-3H3,(H2,24,25,29,30,31)/t8-,9+,10-,16+/m0/s1

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C22H22FN5O7
Molecular Weight	487.44
AlogP	1.2
Hydrogen Bond Acceptor	9.0
Hydrogen Bond Donor	2.0
Number of Rotational Bond	1.0
Polar Surface Area	143.31
Molecular species	NEUTRAL
Aromatic Rings	2.0
Heavy Atoms	35.0

Bioactivity

Mechanism of Action	Action	Reference
DNA gyrase inhibitor	INHIBITOR	PubMed

Assay Description	Organism	Bioactivity	Reference
Fluorescence Polarisation Assay: In a black, 384-well polystyrene assay plate, 30 microliters/well of 5 nM Escherichia coli DNA gyrase A/B tetramer and 130 micrograms/mL of topological^ relaxed plasmid containing the triplex-forming sequence TTCTTCTTCTTCTTCTTCTTCTTCTTC (SEQ ID NO: 1) in an assay buffer consisting of 35 mM Tris-HCI (pH 7.5), 24 mM KCI, 4 mM MgCI2, 2 mM dithiothreitol, 1.8 mM spermidine, 5% (v/v) glycerol, 200 nM bovine serum albumin, 0.8%dimethylsulfoxide, and 0.3 mM ATP were incubated at ambient temperature for (typically 30 minutes) in the absence or presence of 5 -10 different concentrations of test compound. The supercoiling reactions were quenched by the addition of 10 microliters/well of 40 nM oligodeoxynucleotide probe in 3X triplex-forming buffer consisting of 150 mM NaCI, and 150 mM sodium acetate at pH 3.5. The oligodeoxynucleotide probe was 5'-BODIPY-FL-labeled TTCTTCTTC (SEQ ID NO:2). After 60 minutes, the fluorescence anisotropy of the BODIPY- FL was measured in a Tecan Ultra plate.	Escherichia coli	169.0 nM
Inhibition of recombinant Escherichia coli DNA gyrase AB expressed in Escherichia coli BL21 (DE3) using relaxed pJT519 DNA as substrate preincubated for 20 mins followed by 5'-BODIPY-TMR-TTCTTCTTCT addition and measured after 1 hr by fluorescence anisotropy	Escherichia coli	170.0 nM

Cross References

Resources	Reference
ChEMBL	CHEMBL3544978
DrugBank	DB12817
FDA SRS	FWL2263R77
Guide to Pharmacology	10875
PubChem	76685216
SureChEMBL	SCHEMBL15879500

CONTENTS


PREMIER has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 875508. The JU receives support from the EU’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The views reflect only the authors’ perspective and the JU is not responsible for any use that may be made of the information this manuscript contains. Elements of the website have been developed under projects PREMIER and the Biocenter Finland Drug Discovery and Chemical Biology network. CSC-IT is thanked for providing computational resources. Content of the website is provided without guarantee for correctness. Data has been collected and integrated from multiple public sources, for the largest: FDA, HUGO Gene Nomenclature Committee, ChEMBL, IUPHAR/BPS guide to pharmacology, Reactome, UniProt, and Ensembl. Credit is given to Ensembl for collecting species images (provided under public domain licences such as Wikimedia and NHGRI).

PREMIER has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 875508. The JU receives support from the EU’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The views reflect only the authors’ perspective and the JU is not responsible for any use that may be made of the information this manuscript contains.

Elements of the website have been developed under projects PREMIER and the Biocenter Finland Drug Discovery and Chemical Biology network. CSC-IT is thanked for providing computational resources. Content of the website is provided without guarantee for correctness. Data has been collected and integrated from multiple public sources, for the largest: FDA, HUGO Gene Nomenclature Committee, ChEMBL, IUPHAR/BPS guide to pharmacology, Reactome, UniProt, and Ensembl. Credit is given to Ensembl for collecting species images (provided under public domain licences such as Wikimedia and NHGRI).