ETHAMBUTOL DIHYDROCHLORIDE, DL-

Details

Stereochemistry	RACEMIC
Molecular Formula	C10H24N2O2.2ClH
Molecular Weight	277.232
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of ETHAMBUTOL DIHYDROCHLORIDE, DL-

Structure Search

SMILES

Cl.Cl.CC[C@@H](CO)NCCN[C@@H](CC)CO

InChI

InChIKey=AUAHHJJRFHRVPV-BZDVOYDHSA-N

InChI=1S/C10H24N2O2.2ClH/c1-3-9(7-13)11-5-6-12-10(4-2)8-14;;/h9-14H,3-8H2,1-2H3;2*1H/t9-,10-;;/m0../s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/016320s066lbl.pdf
Curator's Comment: Description was created based on several sources, including http://www.drugbank.ca/drugs/DB00330

ETHAMBUTOL HYDROCHLORIDE is an oral chemotherapeutic agent which is specifically effective against actively growing microorganisms of the genus Mycobacterium, including M. tuberculosis. Ethambutol inhibits RNA synthesis and decreases tubercle bacilli replication. Nearly all strains of M. tuberculosis and M. kansasii as well as a number of strains of MAC are sensitive to ethambutol. Ethambutol inhibits arabinosyl transferases which is involved in cell wall biosynthesis. By inhibiting this enzyme, the bacterial cell wall complex production is inhibited. This leads to an increase in cell wall permeability. ETHAMBUTOL HCl is indicated for the treatment of pulmonary tuberculosis. It should not be used as the sole antituberculous drug, but should be used in conjunction with at least one other antituberculous drug.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Probable arabinosyltransferase C 3 Target ID: Probable arabinosyltransferase C Sources: http://www.drugbank.ca/drugs/DB00330	Inhibitor 8297
Probable arabinosyltransferase B 3 Target ID: Probable arabinosyltransferase B Sources: http://www.drugbank.ca/drugs/DB00330	Inhibitor 8297
Arabinosyltransferase A 4 Target ID: CHEMBL1877 Sources: http://www.drugbank.ca/drugs/DB00330	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pulmonary tuberculosis 17 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/016320s066lbl.pdf	Primary		Approved 8429	MYAMBUTOL Approved Use pulmonary tuberculosis Launch Date 1967

C_max

Value	Dose	Co-administered	Analyte	Population
3.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10049268/	25 mg/kg single, oral dose: 25 mg/kg route of administration: Oral experiment type: SINGLE co-administered: aluminum-magnesium antacid	aluminum-magnesium antacid	ETHAMBUTOL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4.5 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10049268/	25 mg/kg single, oral dose: 25 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		ETHAMBUTOL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10049268/	25 mg/kg single, oral dose: 25 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		ETHAMBUTOL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT

AUC

Value	Dose	Co-administered	Analyte	Population
27.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10049268/	25 mg/kg single, oral dose: 25 mg/kg route of administration: Oral experiment type: SINGLE co-administered: aluminum-magnesium antacid	aluminum-magnesium antacid	ETHAMBUTOL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
28 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10049268/	25 mg/kg single, oral dose: 25 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		ETHAMBUTOL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
29.6 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10049268/	25 mg/kg single, oral dose: 25 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		ETHAMBUTOL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT

Doses

Dose	Population	Adverse events
25 mg/kg 1 times / day multiple, oral Recommended Dose: 25 mg/kg, 1 times / day Route: oral Route: multiple Dose: 25 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25861347	unhealthy, 79 years n = 1 Health Status: unhealthy Condition: pulmonary tuberculosis Age Group: 79 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/25861347	Disc. AE: Agranulocytosis... AEs leading to discontinuation/dose reduction: Agranulocytosis (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/25861347

AEs

AE	Significance	Dose	Population
Agranulocytosis	1 patient Disc. AE	25 mg/kg 1 times / day multiple, oral Recommended Dose: 25 mg/kg, 1 times / day Route: oral Route: multiple Dose: 25 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25861347	unhealthy, 79 years n = 1 Health Status: unhealthy Condition: pulmonary tuberculosis Age Group: 79 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/25861347

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 OCT1 512 OCT2 647 OCT3 150 OATP1B1 788 OATP2B1 123 OATP1B3 706 MRP3 157 MRP2 383 MRP4 204 BSEP 402 CYP3A 214 UGT1A1 204 UGT1A4 77 UGT1A6 108 UGT1A9 116 UGT2B7 146 UGT2B15 64	P-gp 1537 OCT1 327 OCT2 355 OCTN1 47 OCTN2 50 OAT3 339 OCT3 80 MATE1 135 MATE2 96

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
OATP1B3 715	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862515/pdf/zac3096.pdf#page=1 Page: 1.0	moderate [IC50 53.9 uM]	likely Comment: Drug-drug interaction index prediction Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862515/pdf/zac3096.pdf#page=1 Page: 1.0
OATP1B1 803	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862515/pdf/zac3096.pdf#page=1 Page: 1.0	moderate [IC50 57.6 uM]	likely Comment: Drug-drug interaction index prediction Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862515/pdf/zac3096.pdf#page=1 Page: 1.0
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	moderate [IC50 8.4 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	moderate [IC50 9.4 uM]
BSEP 403	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	no
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	no
CYP3A 298	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	no
MRP2 475	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no
MRP4 238	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no
UGT1A4 80	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	no
UGT1A6 141	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	no
UGT2B15 64	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	no
OATP2B1 126	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862515/pdf/zac3096.pdf#page=1 Page: 1.0	no	unlikely Comment: Drug-drug interaction index prediction Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862515/pdf/zac3096.pdf#page=1 Page: 1.0
OCT2 648	inhibitor 3277 Sources: https://aac.asm.org/content/aac/57/10/5053.full.pdf#page=1 Page: 1.0	strong [IC50 253.8 uM]	likely Comment: Drug-drug interaction index prediction Sources: https://aac.asm.org/content/aac/57/10/5053.full.pdf#page=1 Page: 1.0
OCT1 543	inhibitor 3277 Sources: https://aac.asm.org/content/aac/57/10/5053.full.pdf#page=1 Page: 1.0	strong [IC50 92.6 uM]	likely Comment: Drug-drug interaction index prediction Sources: https://aac.asm.org/content/aac/57/10/5053.full.pdf#page=1 Page: 1.0
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	strong [Ki 1.4 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	strong [Ki 2.9 uM]
OCT3 150	inhibitor 3277 Sources: https://aac.asm.org/content/aac/57/10/5053.full.pdf#page=1 Page: 1.0	weak [IC50 4100 uM]	likely Comment: Drug-drug interaction index prediction Sources: https://aac.asm.org/content/aac/57/10/5053.full.pdf#page=1 Page: 1.0
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	weak
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	weak
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	weak
UGT1A1 254	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	weak
UGT1A9 121	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	weak
UGT2B7 157	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	weak
MRP3 207	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	yes [IC50 88.2 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
OCTN1 47	substrate 3367 Sources: https://aac.asm.org/content/aac/62/9/e00512-18.full.pdf#page_1 Page: 1.0	major
OCTN2 50	substrate 3367 Sources: https://aac.asm.org/content/aac/62/9/e00512-18.full.pdf#page_1 Page: 1.0	major
OAT3 339	substrate 3367 Sources: https://aac.asm.org/content/aac/62/9/e00512-18.full.pdf#page_4 Page: 4.0	no
MATE2 96	substrate 3367 Sources: https://aac.asm.org/content/aac/60/12/7105.full.pdf#page=1 Page: 1.0	yes
OCT2 355	substrate 3367 Sources: https://aac.asm.org/content/aac/62/9/e00512-18.full.pdf#page_1 Page: 1.0	yes
OCT3 80	substrate 3367 Sources: https://aac.asm.org/content/aac/60/12/7105.full.pdf#page=1 Page: 1.0	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17258938/ Page: 1.0	yes
MATE1 135	substrate 3367 Sources: https://aac.asm.org/content/aac/60/12/7105.full.pdf#page=1 Page: 1.0	yes	likely Comment: DDI index of >0.1 Sources: https://aac.asm.org/content/aac/60/12/7105.full.pdf#page=1 Page: 1.0
OCT1 327	substrate 3367 Sources: https://aac.asm.org/content/aac/62/9/e00512-18.full.pdf#page_1 Page: 1.0	yes	likely Comment: Drug-drug interaction index prediction Sources: https://aac.asm.org/content/aac/62/9/e00512-18.full.pdf#page_1 Page: 1.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4877	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4877
ChemicalBook	CB3324345	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3324345
MolPort	MolPort-006-110-202	https://www.molport.com/shop/molecule-link/MolPort-006-110-202
ZINC	ZINC000019364219	http://zinc15.docking.org/substances/ZINC000019364219
eMolecules	31225919	https://www.emolecules.com/cgi-bin/more?vid=31225919

PubMed

Title	Date	PubMed
A comparative study of daily followed by twice or once weekly regimens of ethambutol and rifampicin in retreatment of patients with pulmonary tuberculosis. The results at 1 year. A cooperative tuberculosis chemotherapy study in Poland.	1975 Mar	1096388
Hepatotoxicity of rifampicin and isoniazid in children.	1975 May	1079531
Ocular toxicity with ethambutol in tuberculosis patients.	1976 Jul	1026648
Antimycobacterial spectrum of sparfloxacin and its activities alone and in association with other drugs against Mycobacterium avium complex growing extracellularly and intracellularly in murine and human macrophages.	1991 Dec	1667250
Chlorpromazine: a drug potentially useful for treating mycobacterial infections.	1992	1288966
Spectrum of drugs against atypical mycobacteria: how valid is the current practice of drug susceptibility testing and the choice of drugs?	1992 Dec	1303690
CI-960 (PD127391 or AM-1091), sparfloxacin, WIN 57273, and isepamicin activity against clinical isolates of Mycobacterium avium-intracellularae complex, M. chelonae, and M. fortuitum.	1992 Feb	1315233
Ocular toxicology.	1994 Dec	10172409
[Experimental study on the antituberculous activity of ofloxacins].	1997 Apr	10072834
Visual evoked responses in ethambutol induced optic neuritis.	1997 Nov	11229182
Disseminated Mycobacterium genavense infection in a patient with acquired immunodeficiency syndrome: first case report in Taiwan.	1999 Jan	10063276
[Optic nerve neuropathy by ethambutol toxicity].	1999 May	11775861
Ethambutol related headache in HIV infection: sensitisation to normal CSF pressure? A case report.	2000 Apr	10847796
A new class of antituberculosis agents.	2000 Aug 24	10966749
Minimal change nephrotic syndrome associated with rifampicin treatment.	2000 Jul	10862648
Activity of poloxamer CRL-1072 against drug-sensitive and resistant strains of Mycobacterium tuberculosis in macrophages and in mice.	2000 Jun	10856678
Leucocytoclastic vasculitis and indinavir.	2000 Nov	11069541
Intrinsic resistance of Mycobacterium tuberculosis to clarithromycin is effectively reversed by subinhibitory concentrations of cell wall inhibitors.	2000 Sep	10980165
Continuous rifampicin administration inducing acute renal failure.	2001 Jan	11209029
Optic neuropathy after treatment with anti-tuberculous drugs in a subject with Leber's hereditary optic neuropathy mutation.	2001 Sep	11596792
Color vision in 42 Congolese patients with tuberculosis receiving ethambutol treatment.	2002	12161991
Bactericidal activities of commonly used antiseptics against multidrug-resistant mycobacterium tuberculosis.	2002	12011515
Antimicrobial activities of clarithromycin, gatifloxacin and sitafloxacin, in combination with various antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex.	2002 Feb	11850167
Rapidly progressive glomerulonephritis due to rifampicin therapy.	2002 Jan	11744817
Trends in the use of antituberculosis drugs in Spain 1993-1998.	2003 Apr-May	12733476
Evaluation of visual functions in patients on ethambutol therapy for tuberculosis: a prospective study.	2003 Dec	15909750
Familial clustering of rifampin-induced acute renal failure.	2003 Dec	14677899
Leber's hereditary optic neuropathy mutations in ethambutol-induced optic neuropathy.	2003 Jan	12527998
Ethambutol and optic neuropathy.	2003 Jul	12948256
Mefloquine, moxifloxacin, and ethambutol are a triple-drug alternative to macrolide-containing regimens for treatment of Mycobacterium avium disease.	2003 Jun 15	12792877
[Unusual therapeutic approach in treatment of pulmonary tuberculosis in six year old girl].	2004	15484863
Pancytopenia due to extensive hemophagocytosis following anti-tubercular treatment.	2004 Feb	14755385
New agents active against Mycobacterium avium complex selected by molecular topology: a virtual screening method.	2004 Jan	14645324
The activity of grepafloxacin in two murine models of Mycobacterium avium infection.	2004 Jun	15290460
Ethambutol-induced optic neuritis in patients with end stage renal disease on hemodialysis: two case reports and literature review.	2004 Mar	15287205
Ethambutol-induced acute renal failure.	2004 May	15102986
Synthesis, antimicrobial activity and molecular modeling studies of halogenated 4-[1H-imidazol-1-yl(phenyl)methyl]-1,5-diphenyl-1H-pyrazoles.	2004 Oct 15	15388173
[Mycobacterium bovis tuberculosis in a female patient with AIDS].	2005 Apr-Jun	16178466
Rapidly developing optic neuritis secondary to ethambutol: possible mechanism of injury.	2005 Jul	16108516
The role of ultrasound and echo-color Doppler in the diagnosis and follow-up of tuberculosis of the transplanted kidney.	2005 Mar	15906799
Differential antibiotic susceptibilities of starved Mycobacterium tuberculosis isolates.	2005 Nov	16251329
Diversity in domain architectures of Ser/Thr kinases and their homologues in prokaryotes.	2005 Sep 19	16171520
[Vision impairment in the course of lung tuberculosis treatment].	2006	16848215
[Meningoencephalitis tuberculosis--primary isolation of resistant M. tuberculosis].	2006	16528937
Fluoroquinolones: an important class of antibiotics against tuberculosis.	2006	16475933
Enhanced susceptibility of multidrug resistant strains of Mycobacterium tuberculosis to granulysin peptides correlates with a reduced fitness phenotype.	2006 Jul	16793311
Leber's hereditary optic neuropathy precipitated by ethambutol.	2006 May-Jun	16767386
Activity of 7-methyljuglone in combination with antituberculous drugs against Mycobacterium tuberculosis.	2006 Nov	16987644
Abnormal multifocal electroretinogram (mfERG) in ethambutol toxicity.	2006 Oct-Dec	17182409
Antituberculous therapy-induced fulminant hepatic failure: successful treatment with liver transplantation and nonstandard antituberculous therapy.	2006 Sep	16933231

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Tuberculosis - Active Initial treatment: 15 mg/kg orally once a day for 6 to 8 weeks with concurrent isoniazid therapy. Retreatment: 25 mg/kg orally once a day for 60 days concurrently with at least one other anti-TB drug. After 60 days, decrease dose to 15 mg/kg orally once a day. As an alternative to single daily dose, a dose of 40 mg/kg orally twice a week or 30 mg/kg orally 3 times a week can be administered. This generally follows 2 weeks of daily therapy.

Route of Administration: Oral

In Vitro Use Guide

The antimycobacterial activity of ethambutol was assessed against Mycobacterium tuberculosis (H37Rv) strain using micro plate Alamar Blue assay (MABA). Compound showed inhibitory activity with MIC value 3.125 ug/mL

Name

Type

Language

ETHAMBUTOL DIHYDROCHLORIDE, DL-

Common Name

English

1-BUTANOL, 2,2'-(1,2-ETHANEDIYLDIIMINO)BIS-, DIHYDROCHLORIDE, (2R,2'R)-REL-

Common Name

English

Code System Code Type Description

CAS

22196-75-4

Created by admin on Fri Dec 15 15:25:27 GMT 2023 , Edited by admin on Fri Dec 15 15:25:27 GMT 2023

PRIMARY

PUBCHEM

14051

Created by admin on Fri Dec 15 15:25:27 GMT 2023 , Edited by admin on Fri Dec 15 15:25:27 GMT 2023

PRIMARY

EPA CompTox

DTXSID50944849

Created by admin on Fri Dec 15 15:25:27 GMT 2023 , Edited by admin on Fri Dec 15 15:25:27 GMT 2023

PRIMARY

FDA UNII

JNG307DJ5X

Created by admin on Fri Dec 15 15:25:27 GMT 2023 , Edited by admin on Fri Dec 15 15:25:27 GMT 2023

PRIMARY

SUBSTANCE RECORD


					JNG307DJ5X

ETHAMBUTOL DIHYDROCHLORIDE, DL-

Details

SMILES

InChI

DescriptionSources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/016320s066lbl.pdfCurator's Comment: Description was created based on several sources, including http://www.drugbank.ca/drugs/DB00330

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Cmax

AUC

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/016320s066lbl.pdf
Curator's Comment: Description was created based on several sources, including http://www.drugbank.ca/drugs/DB00330

C_max

Drug as perpetrator