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Details

Stereochemistry ACHIRAL
Molecular Formula C14H12ClN3O4S2
Molecular Weight 385.846
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of INDISULAM

SMILES

NS(=O)(=O)C1=CC=C(C=C1)S(=O)(=O)NC2=C3NC=C(Cl)C3=CC=C2

InChI

InChIKey=SETFNECMODOHTO-UHFFFAOYSA-N
InChI=1S/C14H12ClN3O4S2/c15-12-8-17-14-11(12)2-1-3-13(14)18-24(21,22)10-6-4-9(5-7-10)23(16,19)20/h1-8,17-18H,(H2,16,19,20)

HIDE SMILES / InChI

Molecular Formula C14H12ClN3O4S2
Molecular Weight 385.846
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Indisulam (also known as E7070) is a sulfonamide derivative patented by Japanese pharmaceutical company Eisai Co. as antitumor agent. Indisulam inhibits cyclin-dependent kinases (CDK), which regulate cell cycle progression and are usually over-expressed in cancerous cells. Inhibition of CDK results in G1/S phase arrest of the cell cycle, and may lead to induction of apoptosis and inhibition of tumor cell proliferation. Preclinical and clinical studies have established the synergy of indisulam with nucleoside analogs as well as topoisomerase inhibitors. These combinations were tolerated with acceptable toxicities, including diarrhea, vomiting, and myelosuppression. In Phase II clinical trials Combination of indisulam with DNA‐damaging agent (idarubicin) and nucleoside analog (cytarabine) in patients with relapsed and refractory AML is effective and largely well tolerated.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
31.0 nM [IC50]
47.0 nM [Ki]
15.0 nM [IC50]
24.0 nM [Ki]

Cmax

ValueDoseCo-administeredAnalytePopulation
1468 ng/mL
10 mg/m² single, intravenous
INDISULAM plasma
Homo sapiens
2044 ng/mL
13 mg/m² single, intravenous
INDISULAM plasma
Homo sapiens
3307 ng/mL
26 mg/m² single, intravenous
INDISULAM plasma
Homo sapiens
7756 ng/mL
52 mg/m² single, intravenous
INDISULAM plasma
Homo sapiens
16324 ng/mL
104 mg/m² single, intravenous
INDISULAM plasma
Homo sapiens
20958 ng/mL
130 mg/m² single, intravenous
INDISULAM plasma
Homo sapiens
18331 ng/mL
160 mg/m² single, intravenous
INDISULAM plasma
Homo sapiens
18815 ng/mL
160 mg/m² single, intravenous
INDISULAM plasma
Homo sapiens
1296 ng/mL
10 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
2228 ng/mL
13 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
3337 ng/mL
26 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
8125 ng/mL
52 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
19050 ng/mL
104 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
34129 ng/mL
130 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
34391 ng/mL
160 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
66835 ng/mL
200 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
117.7 μg/mL
800 mg/m² 1 times / 3 weeks steady-state, intravenous
INDISULAM plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
3374 ng × h/mL
10 mg/m² single, intravenous
INDISULAM plasma
Homo sapiens
4585 ng × h/mL
13 mg/m² single, intravenous
INDISULAM plasma
Homo sapiens
7747 ng × h/mL
26 mg/m² single, intravenous
INDISULAM plasma
Homo sapiens
17041 ng × h/mL
52 mg/m² single, intravenous
INDISULAM plasma
Homo sapiens
50518 ng × h/mL
104 mg/m² single, intravenous
INDISULAM plasma
Homo sapiens
80996 ng × h/mL
130 mg/m² single, intravenous
INDISULAM plasma
Homo sapiens
66453 ng × h/mL
160 mg/m² single, intravenous
INDISULAM plasma
Homo sapiens
137569 ng × h/mL
160 mg/m² single, intravenous
INDISULAM plasma
Homo sapiens
5096 ng × h/mL
10 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
7183 ng × h/mL
13 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
10292 ng × h/mL
26 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
26072 ng × h/mL
52 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
169306 ng × h/mL
104 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
470847 ng × h/mL
130 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
506676 ng × h/mL
160 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
887389 ng × h/mL
200 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
3943 μg × h/mL
800 mg/m² 1 times / 3 weeks steady-state, intravenous
INDISULAM plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
25.98 h
10 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
26.82 h
13 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
25.17 h
26 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
20.2 h
52 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
20.1 h
104 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
26.46 h
130 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
19.67 h
160 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
11.45 h
200 mg/m² 1 times / day steady-state, intravenous
INDISULAM plasma
Homo sapiens
22 h
800 mg/m² 1 times / 3 weeks steady-state, intravenous
INDISULAM plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
single, unknown
INDISULAM plasma
Homo sapiens

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
400 mg/ m^2 on days 1 and 8 of a 28-day cycle
Route of Administration: Intravenous
Substance Class Chemical
Record UNII
WJ98J3NM90
Record Status Validated (UNII)
Record Version