Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C22H38N2 |
| Molecular Weight | 330.5505 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)=CCC\C(C)=C\CNCCNC1C2CC3CC(C2)CC1C3
InChI
InChIKey=JFIBVDBTCDTBRH-REZTVBANSA-N
InChI=1S/C22H38N2/c1-16(2)5-4-6-17(3)7-8-23-9-10-24-22-20-12-18-11-19(14-20)15-21(22)13-18/h5,7,18-24H,4,6,8-15H2,1-3H3/b17-7+
| Molecular Formula | C22H38N2 |
| Molecular Weight | 330.5505 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/25630641
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/25630641
SQ-109 is a [1,2]-diamine-based ethambutol (EMB) analog developed for the treatment of tuberculosis. SQ109 acts by inhibiting MmpL3, a transporter of trehalose monomyclate, which is an important component of cellular wall. The drug was investigated as a monotherapy or in combination with rifampicin in phase II clinical trials in pulmonary tuberculosis patients. The clinical trials, however, did not demonstrate activity of SQ-109 alone or its ability to enhance the activity of rifampicin.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL5440 |
0.36 µM [Ki] | ||
Target ID: P9WJV5 Gene ID: 886752.0 Gene Symbol: mmpL3 Target Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
43.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25630641 |
300 mg 1 times / day single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
SQ-109 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
39.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25630641 |
300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SQ-109 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
45.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25630641 |
300 mg 1 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
SQ-109 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
37.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16432511 |
15 mg/kg single, oral dose: 15 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
SQ-109 plasma | Canis lupus population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
183.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25630641 |
300 mg 1 times / day single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
SQ-109 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
240.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25630641 |
300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SQ-109 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
268.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25630641 |
300 mg 1 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
SQ-109 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
158 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16432511 |
15 mg/kg single, oral dose: 15 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
SQ-109 plasma | Canis lupus population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
11.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16432511 |
15 mg/kg single, oral dose: 15 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
SQ-109 plasma | Canis lupus population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
91.6% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16432511 |
unknown, unknown |
SQ-109 plasma | Rattus norvegicus population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
300 mg 1 times / day multiple, oral Highest studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: Page: p.3 |
unhealthy, ADULT Health Status: unhealthy Condition: tuberculosis Age Group: ADULT Sex: M+F Food Status: FASTED Sources: Page: p.3 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Novel agents in the management of Mycobacterium tuberculosis disease. | 2007 |
|
| Drug therapy of experimental tuberculosis (TB): improved outcome by combining SQ109, a new diamine antibiotic, with existing TB drugs. | 2007 Apr |
|
| Synthesis and evaluation of SQ109 analogues as potential anti-tuberculosis candidates. | 2010 May |
|
| Novel linear diamine disubstituted polycyclic 'cage' derivatives as potential antimycobacterial candidates. | 2011 Dec |
|
| Design, synthesis, and biological evaluation of novel fluorinated ethanolamines. | 2011 Dec 23 |
|
| Head-to-head prenyl tranferases: anti-infective drug targets. | 2012 May 10 |
Patents
Sample Use Guides
In clinical trials against tuberculosis, SQ-109 was administered orally at doses 75-300 mg daily
Route of Administration:
Oral
MIC assays were performed in 96-well round-bottom plates for seven-days. SQ-109 was suspended in DMSO at a final concentration of 10 mM and diluted 100-fold into 7H9-OADC liquid medium containing 0.05% Tween-80. This 100 uM stock was diluted by 2-fold serial dilutions in the same medium in microtiter wells, resulting in 50 uL total volume in each well. In addition to a control lacking drug, the lowest concentration of drug assayed was 0.04 uM (11 dilutions total). M. tuberculosis H37Rv was grown to an optical density [600nm] 0.5 and diluted 1:10 before adding 50 uL to each individual well of the 96-well plates. The final optical density at 600nm was 0.025, and there was no visible growth within the wells of the microtiter plate. Upon incubation for 7 days at 37 °C, growth became apparent, and the MIC was determined to be the lowest concentration that prevents visible growth. MIC for SQ-109 in this assay was 0.2 uM.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 17:45:50 UTC 2023
by
admin
on
Fri Dec 15 17:45:50 UTC 2023
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| Record UNII |
9AU7XUV31A
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| Record Status |
Validated (UNII)
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| Record Version |
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EU-Orphan Drug |
EU/3/07/479
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FDA ORPHAN DRUG |
247307
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502487-67-4
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5274428
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SQ109
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C95706
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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TARGET ORGANISM->INHIBITOR |
Despite its broad structural similarity to EMB retained good activity against EMB-resistant Mtb strains (MIC 2.4 μM, cf. 1.2 μMNagainst H37Rv).
MIC
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| Related Record | Type | Details | ||
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ACTIVE MOIETY |
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