Details
Stereochemistry | ACHIRAL |
Molecular Formula | C19H15NO3S |
Molecular Weight | 337.392 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCS(=O)(=O)C1=CC=C2OC(=NC2=C1)C3=CC=C4C=CC=CC4=C3
InChI
InChIKey=KSGCNXAZROJSNW-UHFFFAOYSA-N
InChI=1S/C19H15NO3S/c1-2-24(21,22)16-9-10-18-17(12-16)20-19(23-18)15-8-7-13-5-3-4-6-14(13)11-15/h3-12H,2H2,1H3
Ezutromid (SMTC-1100) is a small molecule utrophin upregulator. Ezutromid was identified from an iterative analoging approach from initial hits identified using a human muscle-specific utrophin A promoter cell-based assay. It increases both utrophin RNA and protein resulting in a significant reduction in dystrophic symptoms and increased muscle function in dystrophin-deficient mdx mice ( a mouse model of Duchenne muscular dystrophy (DMD)). Ezutromid was deemed safe and well tolerated in a Phase 1a healthy volunteer study and successfully completed a Phase 1b study in DMD boys. Summit Therapeutics is developing Ezutromid for the treatment of Duchenne muscular dystrophy.
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21456623/
Curator's Comment: reference retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25935002
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: P46939 Gene ID: 7402.0 Gene Symbol: UTRN Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/21573153 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
65.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30650257 |
2500 mg 2 times / day multiple, oral dose: 2500 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
EZUTROMID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
122 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25651188 |
200 mg/kg 2 times / day multiple, oral dose: 200 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered: |
EZUTROMID plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT |
|
531 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25651188 |
400 mg/kg single, oral dose: 400 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
EZUTROMID plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT |
|
80.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30650257 |
2500 mg single, oral dose: 2500 mg route of administration: Oral experiment type: SINGLE co-administered: |
EZUTROMID plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: FED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
551 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30650257 |
2500 mg 2 times / day multiple, oral dose: 2500 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
EZUTROMID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
830 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25651188 |
200 mg/kg 2 times / day multiple, oral dose: 200 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered: |
EZUTROMID plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT |
|
4215 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25651188 |
400 mg/kg single, oral dose: 400 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
EZUTROMID plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT |
|
672 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30650257 |
2500 mg single, oral dose: 2500 mg route of administration: Oral experiment type: SINGLE co-administered: |
EZUTROMID plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: FED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
29 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25651188 |
200 mg/kg 2 times / day multiple, oral dose: 200 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered: |
EZUTROMID plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT |
|
9.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25651188 |
400 mg/kg single, oral dose: 400 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
EZUTROMID plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT |
|
6.53 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30650257 |
2500 mg single, oral dose: 2500 mg route of administration: Oral experiment type: SINGLE co-administered: |
EZUTROMID plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: FED |
Doses
Dose | Population | Adverse events |
---|---|---|
400 mg/kg single, oral Highest studied dose Dose: 400 mg/kg Route: oral Route: single Dose: 400 mg/kg Sources: Page: p.701 |
healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: HIGH-FAT Population Size: 6 Sources: Page: p.701 |
|
200 mg/kg 2 times / day multiple, oral Studied dose Dose: 200 mg/kg, 2 times / day Route: oral Route: multiple Dose: 200 mg/kg, 2 times / day Sources: Page: p.701 |
healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: HIGH-FAT Population Size: 6 Sources: Page: p.701 |
|
2500 mg 2 times / day multiple, oral Studied dose Dose: 2500 mg, 2 times / day Route: oral Route: multiple Dose: 2500 mg, 2 times / day Sources: Page: p.7 |
unhealthy, CHILD n = 4 Health Status: unhealthy Condition: Duchenne muscular dystrophy Age Group: CHILD Sex: M+F Food Status: FED Population Size: 4 Sources: Page: p.7 |
Sample Use Guides
A multicenter, Phase 1 study (NCT02056808) enrolled 12 pediatric patients with Duchenne muscular dystrophy, divided equally into three groups (A-C). Group A were given 50 mg/kg on Days 1 and 11, and 50 mg/kg bid on Days 2 to 10. Group B and C received 100 mg/kg on Days 1 and 11; Group B and Group C were given 100 mg/kg bid and 100 mg/kg tid, respectively, on Days 2 to 10.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21573153
In vitro dosing of human myoblasts with Ezutromid (SMT C1100) leads to a 25% increase in utrophin mRNA when compared to vehicle-only dosing after three days of treatment. Treatment of human DMD cells with SMT C1100 lead to a 2-fold increase in utrophin protein levels at an optimal concentration of 0.3 µM after 3 days of treatment.
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FDA ORPHAN DRUG |
351111
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EU-Orphan Drug |
EU/3/08/591
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