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Details

Stereochemistry ABSOLUTE
Molecular Formula C19H19Br2N3O2S
Molecular Weight 513.246
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CRS-3123

SMILES

BrC1=CC(Br)=C2OCC[C@@H](NCCCNC3=CC(=O)C4=C(N3)C=CS4)C2=C1

InChI

InChIKey=NNTYBKTXMKBRFA-CQSZACIVSA-N
InChI=1S/C19H19Br2N3O2S/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)/t14-/m1/s1

HIDE SMILES / InChI

Description
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 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

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
352 ng/mL
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
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
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
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
1550 ng × h/mL
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
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
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
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
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
3 h
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
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
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
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
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
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
PubMed

PubMed

TitleDatePubMed
Spectrum of activity and mode of action of REP3123, a new antibiotic to treat Clostridium difficile infections.
2009 May
New antibiotics for selective treatment of gastrointestinal infection caused by Clostridium difficile.
2010 Oct
Patents

Sample Use Guides

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 10-fold reduction in the sporulation rate in vitro
Name Type Language
CRS-3123
Common Name English
REP3123
Code English
5-((3-(((4R)-6,8-DIBROMO-3,4-DIHYDRO-2H-1-BENZOPYRAN-4-YL)AMINO)PROPYL)AMINO)THIENO(3,2-B)PYRIDIN-7(4H)-ONE
Systematic Name English
REP-3123
Code English
CRS3123
Code English
THIENO(3,2-B)PYRIDIN-7(4H)-ONE, 5-((3-(((4R)-6,8-DIBROMO-3,4-DIHYDRO-2H-1-BENZOPYRAN-4-YL)AMINO)PROPYL)AMINO)-
Systematic Name English
Code System Code Type Description
FDA UNII
2P987FW4E8
Created by admin on Sat Dec 16 10:29:02 GMT 2023 , Edited by admin on Sat Dec 16 10:29:02 GMT 2023
PRIMARY
PUBCHEM
16744283
Created by admin on Sat Dec 16 10:29:02 GMT 2023 , Edited by admin on Sat Dec 16 10:29:02 GMT 2023
PRIMARY
CAS
1013915-71-3
Created by admin on Sat Dec 16 10:29:02 GMT 2023 , Edited by admin on Sat Dec 16 10:29:02 GMT 2023
PRIMARY
CLINICAL_TRIALS.GOV
CRS-3123
Created by admin on Sat Dec 16 10:29:02 GMT 2023 , Edited by admin on Sat Dec 16 10:29:02 GMT 2023
PRIMARY Detailed Description: This is a Phase I, multi-center, placebo-controlled, double-blind, dose-escalation study to evaluate the safety and tolerability of CRS3123, a methionyl-tRNA synthetase inhibitor. Since this is a FIH study of a new class of drugs, the maximum safe starting dose was estimated from the NOAEL from preclinical studies in accordance with FDA guidance documents (FDA Guidance for Industry, July 2005). A very low starting dose has been chosen. In the initial Cohorts, doses of 100, 200 and 400 will be given, all are below the estimated human starting dose. If any significant safety signals are encountered, the investigators will notify the SMC and call for a review. Dose escalation to Cohorts D and E will require a full SMC review of all safety data obtained through Day 7 for the preceding Cohorts. Forty healthy male and female subjects 18 to 45 years, inclusive, will be admitted for an inpatient study. Each subject will receive a single oral dose of CRS3123 or placebo. There will be 8 patients for each cohort (6 active, 2 placebo). The ascending doses are 100, 200, 400, 800 and 1200 mg respectively for cohorts A through E.
DRUG BANK
DB12262
Created by admin on Sat Dec 16 10:29:02 GMT 2023 , Edited by admin on Sat Dec 16 10:29:02 GMT 2023
PRIMARY