Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C19H19Br2N3O2S.2ClH |
Molecular Weight | 586.168 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.Cl.BrC1=CC(Br)=C2OCC[C@@H](NCCCNC3=CC(=O)C4=C(N3)C=CS4)C2=C1
InChI
InChIKey=HZJABMYSJSDCBO-FMOMHUKBSA-N
InChI=1S/C19H19Br2N3O2S.2ClH/c20-11-8-12-14(2-6-26-18(12)13(21)9-11)22-4-1-5-23-17-10-16(25)19-15(24-17)3-7-27-19;;/h3,7-10,14,22H,1-2,4-6H2,(H2,23,24,25);2*1H/t14-;;/m1../s1
Molecular Formula | C19H19Br2N3O2S |
Molecular Weight | 513.246 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
Molecular Formula | ClH |
Molecular Weight | 36.461 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: http://www.crestonepharma.com/index.php/cdi | https://www.ncbi.nlm.nih.gov/pubmed/20698814Curator's Comment: Description was created based on several sources, including
http://adisinsight.springer.com/drugs/800027088 | https://www.ncbi.nlm.nih.gov/pubmed/19258353
Sources: http://www.crestonepharma.com/index.php/cdi | https://www.ncbi.nlm.nih.gov/pubmed/20698814
Curator's Comment: Description was created based on several sources, including
http://adisinsight.springer.com/drugs/800027088 | https://www.ncbi.nlm.nih.gov/pubmed/19258353
CRS-3123, also known as REP-3123, is a methionyl-tRNA synthetase inhibitor potentially for the treatment of enteric infections. CRS-3123 is in Phase 1 clinical development for the treatment of Clostridium difficile Infection (CDI). CRS-3123 is a small molecule protein synthesis inhibitor that acts on the novel target methionyl-tRNA synthetase (MetRS). REP-3123 has been shown to be active in vitro against clinical
isolates of C. difficile including epidemic strains such as B1/
NAP1/027; MIC values of REP-3123 for C. difficile are
typically 0.5 -- 1.0 mg/l. REP-3123 is also active against a range of clinically important aerobic Gram-positive bacteria
including methicillin-susceptible and -resistant Staphylococcus
aureus (MIC90 values of 0.06 and 0.25 mg/l, respectively),
Streptococcus pyogenes (MIC90 0.5 mg/l) and enterococci
(MIC90 =0.03 mg/l), but was not active against aerobic
Gram-negative bacteria such as Enterobacteriaceae and nonfermenting
bacilli (MIC values > 32 mg/l). CRS-3123 has numerous potential advantages over current CDI therapies. In addition to being highly potent against all clinical isolates of C. difficile tested, CRS-3123 has several desirable qualities for the treatment of CDI which include:
Narrow spectrum for C. difficile, which may substantially reduce the disruption of normal intestinal flora compared to current therapies;
Inhibition of toxin production, potentially leading to lower morbidity and mortality;
Inhibition of sporulation, potentially leading to lower rates of transmission and recurrence;
A novel mechanism of action, which means that its use will not compromise the utility of systemic antibiotics while maintaining activity against pre-existing resistance mechanisms.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL614965 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20698814 |
|||
Target ID: CHEMBL352 |
|||
Target ID: CHEMBL356 |
|||
Target ID: CHEMBL612318 |
|||
Target ID: Methionyl-tRNA synthetase, Clostridium difficile Sources: https://www.ncbi.nlm.nih.gov/pubmed/20698814 |
0.02 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
352 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
507 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
654 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
470 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
731 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
3200 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1550 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
2340 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
3560 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
2500 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
4030 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
615 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
4.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
6.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31685472 |
400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CRS-3123 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01551004
CRS-3123 will be supplied in 100 and 200 milligram capsules. Subjects randomized to active drug in Cohorts A through E will receive 100 mg, 200 mg, 400 mg, 800 mg and 1200 mg respectively, as a single oral dose.
Route of Administration:
Oral
MIC values of CRS-3123 for C. difficile are
typically 0.5 -- 1.0 mg/l. CRS-3123 is also active against a range of clinically important aerobic Gram-positive bacteria
including methicillin-susceptible and -resistant Staphylococcus
aureus (MIC90 values of 0.06 and 0.25 mg/l, respectively),
Streptococcus pyogenes (MIC90 0.5 mg/l) and enterococci
(MIC90 =0.03 mg/l). At concentrations of 1 mg/l, CRS-3123 inhibited de novo toxin production in high cell density,
stationary phase cultures of C. difficile and also caused
a > 10-fold reduction in the sporulation rate in vitro
Substance Class |
Chemical
Created
by
admin
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Edited
Sat Dec 16 15:31:23 GMT 2023
by
admin
on
Sat Dec 16 15:31:23 GMT 2023
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Record UNII |
IF2P0Y7Y0R
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Record Status |
Validated (UNII)
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Record Version |
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