ERAVACYCLINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H31FN4O8
Molecular Weight	558.5554
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC3=C(F)C=C(NC(=O)CN4CCCC4)C(O)=C3C(=O)C1=C(O)[C@]5(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@]5([H])C2

InChI

InChIKey=HLFSMUUOKPBTSM-ISIOAQNYSA-N

InChI=1S/C27H31FN4O8/c1-31(2)20-13-8-11-7-12-14(28)9-15(30-16(33)10-32-5-3-4-6-32)21(34)18(12)22(35)17(11)24(37)27(13,40)25(38)19(23(20)36)26(29)39/h9,11,13,20,34,36-37,40H,3-8,10H2,1-2H3,(H2,29,39)(H,30,33)/t11-,13-,20-,27-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf | https://www.drugbank.ca/drugs/DB12329 | https://www.ncbi.nlm.nih.gov/pubmed/29869646

Eravacycline, known as Xerava by Tetraphase Pharmaceuticals, is a fully synthetic fluorocycline antibiotic of the tetracycline class with activity against clinically significant gram-negative, gram-positive aerobic, and facultative bacteria. This includes most of those bacteria resistant to cephalosporins, fluoroquinolones, β-lactam/β-lactamase inhibitors, multidrug-resistant strains, and carbapenem-resistant Enterobacteriaceae, and the majority of anaerobic pathogens. It was first approved by the FDA on August 27, 2018. Eravacycline disrupts bacterial protein synthesis by binding to the 30S ribosomal subunit thus preventing the incorporation of amino acid residues into elongating peptide chains.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Escherichia coli 82 Target ID: CHEMBL354 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22354310	Inhibitor 8297
30S ribosomal protein S4 2 Target ID: P0A7V8 Gene ID: 947793.0 Gene Symbol: rpsD Target Organism: Escherichia coli (strain K12) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26863149 \| https://www.ncbi.nlm.nih.gov/pubmed/22354310	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Intra-abdominal infections 49 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf https://adisinsight.springer.com/drugs/800032231	Curative		Approved 8429	XERAVA Approved Use XERAVA is a tetracycline class antibacterial indicated for the treatment of complicated intra-abdominal infections in patients 18 years of age and older. (1.1) Limitations of Use XERAVA is not indicated for the treatment of complicated urinary tract infections (cUTI). (1.1) To reduce the development of drug -resistant bacteria and maintain the effectiveness of XERAVA and other antibacterial drugs, XERAVA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. (1.2) Launch Date 2018

C_max

Value	Dose	Co-administered	Analyte	Population
2125 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		ERAVACYCLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1825 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf	1 mg/kg 2 times / day steady-state, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: STEADY-STATE co-administered:		ERAVACYCLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
4305 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		ERAVACYCLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
6309 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf	1 mg/kg 2 times / day steady-state, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: STEADY-STATE co-administered:		ERAVACYCLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
20 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		ERAVACYCLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
20 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf	1 mg/kg 2 times / day steady-state, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: STEADY-STATE co-administered:		ERAVACYCLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
15.5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		ERAVACYCLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
15.5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf	1 mg/kg 2 times / day steady-state, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: STEADY-STATE co-administered:		ERAVACYCLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
3 mg/kg 1 times / day single, intravenous Highest studied dose Dose: 3 mg/kg, 1 times / day Route: intravenous Route: single Dose: 3 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	healthy, 18–48 years n = 42 Health Status: healthy Age Group: 18–48 years Sex: M+F Population Size: 42 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	Other AEs: Nausea, Vomiting... Other AEs: Nausea (grade 1-2, >10) Vomiting (grade 1-2, <10%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/
1.5 mg/kg 1 times / day single, intravenous MTD Dose: 1.5 mg/kg, 1 times / day Route: intravenous Route: single Dose: 1.5 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	healthy, 18–48 years n = 42 Health Status: healthy Age Group: 18–48 years Sex: M+F Population Size: 42 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/
1 mg/kg 1 times / day single, intravenous Recommended Dose: 1 mg/kg, 1 times / day Route: intravenous Route: single Dose: 1 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	healthy, 18–48 years n = 42 Health Status: healthy Age Group: 18–48 years Sex: M+F Population Size: 42 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	Disc. AE: Pyrexia... AEs leading to discontinuation/dose reduction: Pyrexia (2.4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/
0.25 mg/kg 1 times / day single, intravenous Dose: 0.25 mg/kg, 1 times / day Route: intravenous Route: single Dose: 0.25 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	healthy, 18–48 years n = 42 Health Status: healthy Age Group: 18–48 years Sex: M+F Population Size: 42 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	Disc. AE: Pyrexia... AEs leading to discontinuation/dose reduction: Pyrexia (2.4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/
1.5 mg/kg 1 times / day single, intravenous (min) Dose: 1.5 mg/kg, 1 times / day Route: intravenous Route: single Dose: 1.5 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf	healthy, 18–48 years n = 42 Health Status: healthy Age Group: 18–48 years Sex: M+F Population Size: 42 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf	DLT: Nausea, Vomiting... Dose limiting toxicities: Nausea Vomiting Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf
1 mg/kg 2 times / day multiple, intravenous MTD\|Highest studied dose Dose: 1 mg/kg, 2 times / day Route: intravenous Route: multiple Dose: 1 mg/kg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	healthy, 19–50 years n = 24 Health Status: healthy Age Group: 19–50 years Sex: M+F Population Size: 24 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	Disc. AE: Phlebitis superficial... AEs leading to discontinuation/dose reduction: Phlebitis superficial (4.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/
1 mg/kg 2 times / day multiple, intravenous Recommended Dose: 1 mg/kg, 2 times / day Route: intravenous Route: multiple Dose: 1 mg/kg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	healthy, 19–50 years n = 24 Health Status: healthy Age Group: 19–50 years Sex: M+F Population Size: 24 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	Disc. AE: Decreased appetite, Nausea... AEs leading to discontinuation/dose reduction: Decreased appetite (4.2%) Nausea (4.2%) Vomiting (4.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/

AEs

AE	Significance	Dose	Population
Vomiting	grade 1-2, <10%	3 mg/kg 1 times / day single, intravenous Highest studied dose Dose: 3 mg/kg, 1 times / day Route: intravenous Route: single Dose: 3 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	healthy, 18–48 years n = 42 Health Status: healthy Age Group: 18–48 years Sex: M+F Population Size: 42 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/
Nausea	grade 1-2, >10	3 mg/kg 1 times / day single, intravenous Highest studied dose Dose: 3 mg/kg, 1 times / day Route: intravenous Route: single Dose: 3 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	healthy, 18–48 years n = 42 Health Status: healthy Age Group: 18–48 years Sex: M+F Population Size: 42 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/
Pyrexia	2.4% Disc. AE	1 mg/kg 1 times / day single, intravenous Recommended Dose: 1 mg/kg, 1 times / day Route: intravenous Route: single Dose: 1 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	healthy, 18–48 years n = 42 Health Status: healthy Age Group: 18–48 years Sex: M+F Population Size: 42 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/
Pyrexia	2.4% Disc. AE	0.25 mg/kg 1 times / day single, intravenous Dose: 0.25 mg/kg, 1 times / day Route: intravenous Route: single Dose: 0.25 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	healthy, 18–48 years n = 42 Health Status: healthy Age Group: 18–48 years Sex: M+F Population Size: 42 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/
Nausea	DLT	1.5 mg/kg 1 times / day single, intravenous (min) Dose: 1.5 mg/kg, 1 times / day Route: intravenous Route: single Dose: 1.5 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf	healthy, 18–48 years n = 42 Health Status: healthy Age Group: 18–48 years Sex: M+F Population Size: 42 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf
Vomiting	DLT	1.5 mg/kg 1 times / day single, intravenous (min) Dose: 1.5 mg/kg, 1 times / day Route: intravenous Route: single Dose: 1.5 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf	healthy, 18–48 years n = 42 Health Status: healthy Age Group: 18–48 years Sex: M+F Population Size: 42 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf
Phlebitis superficial	4.2% Disc. AE	1 mg/kg 2 times / day multiple, intravenous MTD\|Highest studied dose Dose: 1 mg/kg, 2 times / day Route: intravenous Route: multiple Dose: 1 mg/kg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	healthy, 19–50 years n = 24 Health Status: healthy Age Group: 19–50 years Sex: M+F Population Size: 24 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/
Decreased appetite	4.2% Disc. AE	1 mg/kg 2 times / day multiple, intravenous Recommended Dose: 1 mg/kg, 2 times / day Route: intravenous Route: multiple Dose: 1 mg/kg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	healthy, 19–50 years n = 24 Health Status: healthy Age Group: 19–50 years Sex: M+F Population Size: 24 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/
Nausea	4.2% Disc. AE	1 mg/kg 2 times / day multiple, intravenous Recommended Dose: 1 mg/kg, 2 times / day Route: intravenous Route: multiple Dose: 1 mg/kg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	healthy, 19–50 years n = 24 Health Status: healthy Age Group: 19–50 years Sex: M+F Population Size: 24 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/
Vomiting	4.2% Disc. AE	1 mg/kg 2 times / day multiple, intravenous Recommended Dose: 1 mg/kg, 2 times / day Route: intravenous Route: multiple Dose: 1 mg/kg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/	healthy, 19–50 years n = 24 Health Status: healthy Age Group: 19–50 years Sex: M+F Population Size: 24 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30150464/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP3A4/5 278 P-gp 1461 BCRP 699 BSEP 402 OATP1B1 788 OATP1B3 706 OAT1 599 OAT3 642 OCT1 512 OCT2 647 MATE1 306 MATE2 263	CYP3A4/5 85 UGT 192 CYP3A 191 P-gp 1537 BCRP 561 BSEP 52 OATP1B1 406 OATP1B3 350 OAT1 326 OAT3 339 OCT1 327 OCT2 355 MATE1 135 MATE2 96	CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=76 Page: 76.0	no
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=76 Page: 76.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=76 Page: 76.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=76 Page: 76.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=76 Page: 76.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=76 Page: 76.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=76 Page: 76.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=76 Page: 76.0	no
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=76 Page: 76.0	no
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=76 Page: 76.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=76 Page: 76.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=76 Page: 76.0	no
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=76 Page: 76.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=76 Page: 76.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	weak [Inhibition 85.6 uM]
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=76 Page: 76,88	yes [Inhibition 36 uM]
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=76 Page: 76,88	yes [Inhibition 36 uM]
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=76 Page: 76,88	yes [Inhibition 36 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf#page=13 Page: 13.0	no
BSEP 52	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf#page=13 Page: 13.0	no
MATE1 135	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf#page=13 Page: 13.0	no
MATE2 96	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf#page=13 Page: 13.0	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf#page=13 Page: 13.0	no
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf#page=13 Page: 13.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf#page=13 Page: 13.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf#page=13 Page: 13.0	no
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf#page=13 Page: 13.0	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf#page=13 Page: 13.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf#page=13 Page: 13.0	no
UGT 192	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes
CYP3A 191	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf#page=13 Page: 13.0	yes	yes (co-administration study) Comment: Concomitant use of itraconazole (strong CYP3A inhibitor) increased eravacycline Cmax by 5% and AUC by 32%, and decreased eravacycline clearance by 32% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf#page=13 Page: 13.0
CYP3A4/5 85	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf#page=13 Page: 13.0	yes	yes (co-administration study) Comment: Concomitant use of rifampin (strong CYP3A4/3A5 inducer) decreased eravacycline AUC by 35% and increased eravacycline clearance by 54% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211109lbl.pdf#page=13 Page: 13.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211109Orig1s000MultidisciplineR.pdf#page=40 Page: 40.0

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA008ZRJ	https://www.aablocks.com/goods/Goods/detail?id=AA008ZRJ
Achemtek	0102-028649	http://www.achemtek.com/1207283-85-9
BioSynth	J-690064	https://www.biosynth.com/en/products/all-products/products/J-690077.html
Chem Scene	CS-7564	http://www.chemscene.com/1207283-85-9.html
ChemFish Tokyo co.,ltd	54726192	http://www.chemfish.co.jp/index.php?id=4631&project=product
ChemShuttle	169624	http://www.chemshuttle.com/catalogsearch/result/?q=1207283-85-9&cat=
Chemspace	CSSB00102419706	https://chem-space.com/CSSB00102419706
Excenen	EX-A751	http://www.excenen.com/searchresultlist.php?id=1207283-85-9
Hairui	ERSA029	http://www.hairuichem.com/en/product/1207283-85-9.html
Lab Network	LN01297610	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01297610
MedChem Express	HY-16980	https://www.medchemexpress.com/Eravacycline.html
MuseChem	I006700	https://www.musechem.com/product/I006700.html
abcr GmbH	AB402282	http://www.abcr.com/shop/en/AB402282
eNovation Chemicals	D516656	https://www.enovationchem.com/ProductDetails.asp?ProductID=D516656

PubMed

Title	Date	PubMed
Fluorocyclines. 1. 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline: a potent, broad spectrum antibacterial agent.	2012 Jan 26	22148514

Patents

Sample Use Guides

In Vivo Use Guide

Administer XERAVA for injection 1 mg/kg by intravenous infusion over approximately 60 minutes every 12 hours for a total duration of 4 to 14 days. (2.1) • Severe Hepatic Impairment (Child Pugh C): 1 mg/kg XERAVA every 12 hours on Day 1, then 1 mg/kg every 24 hours starting on Day 2 for a total duration of 4 to 14 days. (2.2) • Concomitant Use of a Strong Cytochrome P450 Isoenzymes (CYP)3A Inducer: 1.5 mg/kg XERAVA every 12 hours for a total duration of 4 to 14 days. (2.3) For injection: 50 mg of eravacycline (equivalent to 63.5 mg eravacy cline dihydrochloride) as a lyophilized powder in a single-dose vial for reconstitution and further dilution.

Route of Administration: Intravenous

In Vitro Use Guide

In vitro activity data from Tetraphase Pharmaceuticals studies on the following groups of combined bacterial species: Enterobacteriaceae, 5975 isolates, MIC90 0.5 mcg/mL, ECOV 1 ug/mL All Enterococcus spp., 1403 isolates, MIC90 0.06 ug/mL, ECOV 0.25 ug/mL All Viridans Group Streptococcus, 414 isolates, MIC90 0.06 ug/mL, ECOV 0.12 ug/mL Anaerobes, 1190 isolates, MIC90 1 ug/mL, ECOV 1 ug/mL

Name

Type

Language

ERAVACYCLINE

Official Name

English

1-PYRROLIDINEACETAMIDE, N-((5AR,6AS,7S,10AS)-9-(AMINOCARBONYL)-7-(DIMETHYLAMINO)-4-FLUORO-5,5A,6,6A,7,10,10A,12-OCTAHYDRO-1,8,10A,11-TETRAHYDROXY-10,12-DIOXO-2-NAPHTHACENYL)-

Systematic Name

English

ERAVACYCLINE [USAN]

Common Name

English

Eravacycline [WHO-DD]

Common Name

English

TP-434

Code

English

eravacycline [INN]

Common Name

English

ERAVACYCLINE [MI]

Common Name

English

4S,4AS,5AR,12AS)-4-(DIMETHYLAMINO)-7-FLUORO-3,10,12,12A-TETRAHYDROXY-1,11-DIOXO-9-((PYRROLIDIN-1-YLACETYL)AMINO)-1,4,4A,5,5A,6,11,12A-OCTAHYDROTETRACENE-2-CARBOXAMIDE

Systematic Name

English

(4S,4AS,5AR,12AS)-4-(DIMETHYLAMINO)-7-FLUORO-3,10,12,12ATETRAHYDROXY-1,11-DIOXO-9-(2-(PYRROLIDIN-1-YL)ACETAMIDO)-1,4,4A,5,5A,6,11,12A-OCTAHYDROTETRACENE-2-CARBOXAMIDE

Systematic Name

English

Classification Tree Code System Code

WHO-ATC

J01AA13