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Details

Stereochemistry ACHIRAL
Molecular Formula C20H19N4O3.Br
Molecular Weight 443.2941
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SEPANTRONIUM BROMIDE

SMILES

Cc1[n+](CCOC)c2c(C(=O)c3ccccc3C2=O)n1Cc4cnccn4.[Br-]

InChI

InChIKey=QBIYUDDJPRGKNJ-UHFFFAOYSA-M
InChI=1S/C20H19N4O3.BrH/c1-13-23(9-10-27-2)17-18(24(13)12-14-11-21-7-8-22-14)20(26)16-6-4-3-5-15(16)19(17)25;/h3-8,11H,9-10,12H2,1-2H3;1H/q+1;/p-1

HIDE SMILES / InChI

Molecular Formula BrH
Molecular Weight 80.9115
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C20H19N4O3
Molecular Weight 363.3906
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Sepantronium bromide (YM155) is a selective survivin suppressant that exhibits potent antitumor activities by inducing apoptosis and autophagy in various types of cancer. Sepantronium bromide inhibited the growth of various human cancer cell lines in vitro with GI50 values in the low nM range. Sepantronium bromide blocked the growth of 119 human cancer cell lines, with the greatest inhibition in lines derived from non-Hodgkin's lymphoma, hormone-refractory prostate cancer, ovarian cancer, sarcoma, non-small-cell lung cancer, breast cancer, leukemia, and melanoma, with an average GI50 of 15 nM. Sepantronium bromide inhibited the growth of tumor cell lines regardless of their p53 status and demonstrated significant antitumor activity in 5 mice xenograft models. It also caused tumor regressions in vivo, possibly by its effects in reducing intratumoral survivin expression levels and increasing apoptosis. Sepantronium Bromide had been in phase II clinical trials by Astellas for the treatment of prostate cancer, melanoma, non-Hodgkin's lymphoma, breast cancer, diffuse large B cell lymphoma, non-small cell lung cancer (NSCLC) and other solid tumors. This compound had also been in clinical trials by National Cancer Institute (NCI) for the treatment of solid tumors (phase I) and advanced non-small cell lung cancer (NSCLC) (phase II). However, all these researches about this compound for all indications were discontinued.

CNS Activity

Curator's Comment:: Sepantronium has minimal blood-brain barrier penetration

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
10.7 ng/mL
4.8 mg/m² 1 times / day steady-state, intravenous
dose: 4.8 mg/m²
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
SEPANTRONIUM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1439 ng × h/mL
4.8 mg/m² 1 times / day steady-state, intravenous
dose: 4.8 mg/m²
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
SEPANTRONIUM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
26.3 h
4.8 mg/m² 1 times / day steady-state, intravenous
dose: 4.8 mg/m²
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
SEPANTRONIUM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
10.6 mg/m2/day 1 times / day steady-state, intravenous
Highest studied dose
Dose: 10.6 mg/m2/day, 1 times / day
Route: intravenous
Route: steady-state
Dose: 10.6 mg/m2/day, 1 times / day
Sources: Page: p.3874
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.3874
DLT: Serum creatinine increased...
Other AEs: Lymphocytopenia, Lymphocytopenia...
Dose limiting toxicities:
Serum creatinine increased (40%)
Other AEs:
Lymphocytopenia (grade 4, 20%)
Lymphocytopenia (grade 3-4, 80%)
Sources: Page: p.3874
4.8 mg/m2/day 1 times / day steady-state, intravenous
MTD
Dose: 4.8 mg/m2/day, 1 times / day
Route: intravenous
Route: steady-state
Dose: 4.8 mg/m2/day, 1 times / day
Sources: Page: p.5200
unhealthy, ADULT
n = 25
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources: Page: p.5200
DLT: Febrile neutropenia, Stomatitis...
Dose limiting toxicities:
Febrile neutropenia (grade 4, 4%)
Stomatitis (grade 3, 4%)
Sources: Page: p.5200
8 mg/m2/day 1 times / day steady-state, intravenous
MTD
Dose: 8 mg/m2/day, 1 times / day
Route: intravenous
Route: steady-state
Dose: 8 mg/m2/day, 1 times / day
Sources: Page: p.3874
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.3874
6 mg/m2/day 1 times / day steady-state, intravenous
Studied dose
Dose: 6 mg/m2/day, 1 times / day
Route: intravenous
Route: steady-state
Dose: 6 mg/m2/day, 1 times / day
Sources: Page: p.5200
unhealthy, ADULT
n = 2
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2
Sources: Page: p.5200
DLT: Neutropenia, Stomatitis...
Disc. AE: Acute tubular necrosis...
Dose limiting toxicities:
Neutropenia (grade 4, 50%)
Stomatitis (grade 2-3, 100%)
Serum creatinine increased (100%)
AEs leading to
discontinuation/dose reduction:
Acute tubular necrosis (50%)
Sources: Page: p.5200
AEs

AEs

AESignificanceDosePopulation
Serum creatinine increased 40%
DLT
10.6 mg/m2/day 1 times / day steady-state, intravenous
Highest studied dose
Dose: 10.6 mg/m2/day, 1 times / day
Route: intravenous
Route: steady-state
Dose: 10.6 mg/m2/day, 1 times / day
Sources: Page: p.3874
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.3874
Lymphocytopenia grade 3-4, 80%
10.6 mg/m2/day 1 times / day steady-state, intravenous
Highest studied dose
Dose: 10.6 mg/m2/day, 1 times / day
Route: intravenous
Route: steady-state
Dose: 10.6 mg/m2/day, 1 times / day
Sources: Page: p.3874
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.3874
Lymphocytopenia grade 4, 20%
10.6 mg/m2/day 1 times / day steady-state, intravenous
Highest studied dose
Dose: 10.6 mg/m2/day, 1 times / day
Route: intravenous
Route: steady-state
Dose: 10.6 mg/m2/day, 1 times / day
Sources: Page: p.3874
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.3874
Stomatitis grade 3, 4%
DLT
4.8 mg/m2/day 1 times / day steady-state, intravenous
MTD
Dose: 4.8 mg/m2/day, 1 times / day
Route: intravenous
Route: steady-state
Dose: 4.8 mg/m2/day, 1 times / day
Sources: Page: p.5200
unhealthy, ADULT
n = 25
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources: Page: p.5200
Febrile neutropenia grade 4, 4%
DLT
4.8 mg/m2/day 1 times / day steady-state, intravenous
MTD
Dose: 4.8 mg/m2/day, 1 times / day
Route: intravenous
Route: steady-state
Dose: 4.8 mg/m2/day, 1 times / day
Sources: Page: p.5200
unhealthy, ADULT
n = 25
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources: Page: p.5200
Serum creatinine increased 100%
DLT, Disc. AE
6 mg/m2/day 1 times / day steady-state, intravenous
Studied dose
Dose: 6 mg/m2/day, 1 times / day
Route: intravenous
Route: steady-state
Dose: 6 mg/m2/day, 1 times / day
Sources: Page: p.5200
unhealthy, ADULT
n = 2
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2
Sources: Page: p.5200
Acute tubular necrosis 50%
Disc. AE
6 mg/m2/day 1 times / day steady-state, intravenous
Studied dose
Dose: 6 mg/m2/day, 1 times / day
Route: intravenous
Route: steady-state
Dose: 6 mg/m2/day, 1 times / day
Sources: Page: p.5200
unhealthy, ADULT
n = 2
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2
Sources: Page: p.5200
Stomatitis grade 2-3, 100%
DLT, Disc. AE
6 mg/m2/day 1 times / day steady-state, intravenous
Studied dose
Dose: 6 mg/m2/day, 1 times / day
Route: intravenous
Route: steady-state
Dose: 6 mg/m2/day, 1 times / day
Sources: Page: p.5200
unhealthy, ADULT
n = 2
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2
Sources: Page: p.5200
Neutropenia grade 4, 50%
DLT, Disc. AE
6 mg/m2/day 1 times / day steady-state, intravenous
Studied dose
Dose: 6 mg/m2/day, 1 times / day
Route: intravenous
Route: steady-state
Dose: 6 mg/m2/day, 1 times / day
Sources: Page: p.5200
unhealthy, ADULT
n = 2
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2
Sources: Page: p.5200
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive [IC50 16.6261 uM]
weak [IC50 108 uM]
yes [IC50 15.9 uM]
yes [IC50 23.8 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
YM155, a novel small-molecule survivin suppressant, induces regression of established human hormone-refractory prostate tumor xenografts.
2007 Sep 1
Combination of YM155, a survivin suppressant with a STAT3 inhibitor: a new strategy to treat diffuse large B-cell lymphoma.
2013 Sep
Therapeutic potential of sepantronium bromide YM155 in gemcitabine-resistant human urothelial carcinoma cells.
2014 Feb
Dual induction of apoptotic and autophagic cell death by targeting survivin in head neck squamous cell carcinoma.
2015 May 28
Patents

Patents

Sample Use Guides

Solid tumors treatment: Phase I: Doses were given at different dose levels until the maximum tolerated dose (MTD) was reached. Dose level 1: 3.6 mg/m^2, dose level 2:5 mg/m^2 , dose level 3:6 mg/m^2, dose level 4:8 mg/m^2, dose level 5:10 mg/m^2 (MTD), dose level 6:12 mg/m^2. Doses were given by continuous intravenous infusion over 72 hours every 21 days.Three patients were enrolled at each dose level in the absence of dose limiting toxicity (DLT). A DLT is defined as adverse events occurring during the first cycle of therapy (e.g. every 21 days). Phase II: 10 mg/m^2 (MTD)intravenous infusion over 72 hours every 21 days.
Route of Administration: Intravenous
Sepantronium bromide (YM155) suppressed the expression of survivin and induced apoptosis in PC-3 and PPC-1 human HRPC cell lines at 10 nmol/L. In contrast, YM155 up to 100 nmol/L showed little effect on expression levels of other IAP- or Bcl-2-related proteins.
Substance Class Chemical
Created
by admin
on Sat Jun 26 05:13:50 UTC 2021
Edited
by admin
on Sat Jun 26 05:13:50 UTC 2021
Record UNII
7H5Q4J1CM5
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SEPANTRONIUM BROMIDE
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
SEPANTRONIUM BROMIDE [USAN]
Common Name English
YM 155
Code English
SEPANTRONIUM BROMIDE [JAN]
Common Name English
YM155
Code English
SEPANTRONIUM BROMIDE [WHO-DD]
Common Name English
YM-155
Code English
1H-NAPHTH(2,3-D)IMIDAZOLIUM, 4,9-DIHYDRO-1-(2-METHOXYETHYL)-2-METHYL-4,9-DIOXO-3-(2-PYRAZINYLMETHYL)-, BROMIDE (1:1)
Systematic Name English
SEPANTRONIUM BROMIDE [INN]
Common Name English
1-(2-METHOXYETHYL)-2-METHYL-4,9-DIOXO-3-((PYRAZIN-2-YL)METHYL)-4,9-DIHYDRO-1H-NAPHTHO(2,3-D)IMIDAZOLIUM BROMIDE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C2189
Created by admin on Sat Jun 26 05:13:50 UTC 2021 , Edited by admin on Sat Jun 26 05:13:50 UTC 2021
Code System Code Type Description
FDA UNII
7H5Q4J1CM5
Created by admin on Sat Jun 26 05:13:50 UTC 2021 , Edited by admin on Sat Jun 26 05:13:50 UTC 2021
PRIMARY
NCI_THESAURUS
C61091
Created by admin on Sat Jun 26 05:13:50 UTC 2021 , Edited by admin on Sat Jun 26 05:13:50 UTC 2021
PRIMARY
EVMPD
SUB177829
Created by admin on Sat Jun 26 05:13:50 UTC 2021 , Edited by admin on Sat Jun 26 05:13:50 UTC 2021
PRIMARY
EPA CompTox
781661-94-7
Created by admin on Sat Jun 26 05:13:50 UTC 2021 , Edited by admin on Sat Jun 26 05:13:50 UTC 2021
PRIMARY
CAS
781661-94-7
Created by admin on Sat Jun 26 05:13:50 UTC 2021 , Edited by admin on Sat Jun 26 05:13:50 UTC 2021
PRIMARY
ChEMBL
CHEMBL2110734
Created by admin on Sat Jun 26 05:13:50 UTC 2021 , Edited by admin on Sat Jun 26 05:13:50 UTC 2021
PRIMARY
INN
9463
Created by admin on Sat Jun 26 05:13:50 UTC 2021 , Edited by admin on Sat Jun 26 05:13:50 UTC 2021
PRIMARY
PUBCHEM
11178236
Created by admin on Sat Jun 26 05:13:50 UTC 2021 , Edited by admin on Sat Jun 26 05:13:50 UTC 2021
PRIMARY
MESH
C523798
Created by admin on Sat Jun 26 05:13:50 UTC 2021 , Edited by admin on Sat Jun 26 05:13:50 UTC 2021
PRIMARY
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