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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
Structure of CRS-3123 DIHYDROCHLORIDE

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

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
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 DIHYDROCHLORIDE
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)-, HYDROCHLORIDE (1:2)
Common Name English
CRS3123 DIHYDROCHLORIDE
Code English
Code System Code Type Description
CAS
1013915-99-5
Created by admin on Sat Dec 16 15:31:23 GMT 2023 , Edited by admin on Sat Dec 16 15:31:23 GMT 2023
PRIMARY
PUBCHEM
24762985
Created by admin on Sat Dec 16 15:31:23 GMT 2023 , Edited by admin on Sat Dec 16 15:31:23 GMT 2023
PRIMARY
FDA UNII
IF2P0Y7Y0R
Created by admin on Sat Dec 16 15:31:23 GMT 2023 , Edited by admin on Sat Dec 16 15:31:23 GMT 2023
PRIMARY