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Details

Stereochemistry ACHIRAL
Molecular Formula 2C23H21N7O.4CH4O3S.H2O
Molecular Weight 1225.356
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ENTOSPLETINIB DIMESYLATE HEMIHYDRATE

SMILES

O.CS(O)(=O)=O.CS(O)(=O)=O.CS(O)(=O)=O.CS(O)(=O)=O.C1CN(CCO1)C2=CC=C(NC3=NC(=CN4C=CN=C34)C5=CC=C6C=NNC6=C5)C=C2.C7CN(CCO7)C8=CC=C(NC9=NC(=CN%10C=CN=C9%10)C%11=CC=C%12C=NNC%12=C%11)C=C8

InChI

InChIKey=ZWWMUTXYOBTAPV-UHFFFAOYSA-N
InChI=1S/2C23H21N7O.4CH4O3S.H2O/c2*1-2-17-14-25-28-20(17)13-16(1)21-15-30-8-7-24-23(30)22(27-21)26-18-3-5-19(6-4-18)29-9-11-31-12-10-29;4*1-5(2,3)4;/h2*1-8,13-15H,9-12H2,(H,25,28)(H,26,27);4*1H3,(H,2,3,4);1H2

HIDE SMILES / InChI
Molecular Formula C23H21N7O
Molecular Weight 411.4591
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula CH4O3S
Molecular Weight 96.106
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800032822 | https://www.ncbi.nlm.nih.gov/pubmed/25696919

Entospletinib (GS-9973) is an adenosine triphosphate competitive inhibitor of Syk that disrupts kinase activity, which is currently in clinical trials for multiple B-cell malignancies. The most common treatment-emergent serious adverse events included dyspnea, pneumonia, febrile neutropenia, dehydration, and pyrexia.

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 26.0 nM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2799 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27785737
1200 mg 2 times / day multiple, oral
dose: 1200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ENTOSPLETINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
3427 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27785737
1200 mg 2 times / day multiple, oral
dose: 1200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ENTOSPLETINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1059.8 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27785737
1200 mg single, oral
dose: 1200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ENTOSPLETINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
22788 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27785737
1200 mg 2 times / day multiple, oral
dose: 1200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ENTOSPLETINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
26775 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27785737
1200 mg 2 times / day multiple, oral
dose: 1200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ENTOSPLETINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
9744.4 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27785737
1200 mg single, oral
dose: 1200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ENTOSPLETINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.95 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27785737
1200 mg 2 times / day multiple, oral
dose: 1200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ENTOSPLETINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
13.9 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27785737
1200 mg 2 times / day multiple, oral
dose: 1200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ENTOSPLETINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
9.59 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27785737
1200 mg single, oral
dose: 1200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ENTOSPLETINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
1200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/27785737
Page: p.199
healthy, ADULT
n = 8
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/27785737
Page: p.199
Sources:
https://pubmed.ncbi.nlm.nih.gov/27785737
Page: p.199
800 mg 2 times / day multiple, oral
Studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 800 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25696919
unhealthy, ADULT
n = 186
Health Status: unhealthy
Condition: chronic lymphocytic leukemia
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 186
Sources:
https://pubmed.ncbi.nlm.nih.gov/25696919
Disc. AE: Fatigue, ALT increased...
AEs leading to
discontinuation/dose reduction:
Fatigue (2.2%)
ALT increased (1.6%)
Headache (1.6%)
AST increased (1%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/25696919
AEs

AEs

AESignificanceDosePopulation
AST increased 1%
Disc. AE
800 mg 2 times / day multiple, oral
Studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 800 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25696919
unhealthy, ADULT
n = 186
Health Status: unhealthy
Condition: chronic lymphocytic leukemia
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 186
Sources:
https://pubmed.ncbi.nlm.nih.gov/25696919
ALT increased 1.6%
Disc. AE
800 mg 2 times / day multiple, oral
Studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 800 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25696919
unhealthy, ADULT
n = 186
Health Status: unhealthy
Condition: chronic lymphocytic leukemia
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 186
Sources:
https://pubmed.ncbi.nlm.nih.gov/25696919
Headache 1.6%
Disc. AE
800 mg 2 times / day multiple, oral
Studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 800 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25696919
unhealthy, ADULT
n = 186
Health Status: unhealthy
Condition: chronic lymphocytic leukemia
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 186
Sources:
https://pubmed.ncbi.nlm.nih.gov/25696919
Fatigue 2.2%
Disc. AE
800 mg 2 times / day multiple, oral
Studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 800 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25696919
unhealthy, ADULT
n = 186
Health Status: unhealthy
Condition: chronic lymphocytic leukemia
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 186
Sources:
https://pubmed.ncbi.nlm.nih.gov/25696919
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
1587
inhibitor
1767

substrate
1037
inhibitor
1852

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP2C19
1478

CYP1A2
1524

UGT1A1
204

OATP1B1
788

OATP1B3
706

BCRP
699

P-gp
1461
CYP3A
191

HLM
31
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
1692
 unspecified [IC50 >10 uM]
CYP2C19
1553
 unspecified [IC50 >10 uM]
CYP2C9
1819
 unspecified [IC50 >10 uM]
CYP2D6
1891
 unspecified [IC50 >10 uM]
CYP3A4
1925
 unspecified [IC50 >10 uM]
UGT1A1
254
 yes [IC50 ~2.5 uM]
BCRP
773
 yes
OATP1B1
803
 yes
OATP1B3
715
 yes
P-gp
1650
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
HLM
31
 yes
CYP2C9
1037
 yes
yes (co-administration study)
Comment: Fluconazole increased Cmax and AUCtau by 32% and 41%.
CYP3A
191
 yes
yes (co-administration study)
Comment: Rifampicin decreased Cmax and AUCtau by 58% and 71%.
Sourcing

Sourcing

Vendor/AggregatorIDURL
001 Chemical
DY443093
https://www.001chemical.com/chem/search?q=DY443093
1PlusChem LLC
1P000K85
https://www.1pchem.com/search?query=1P000K85
AK Scientific
2440AH
https://aksci.com/item_detail.php?cat=2440AH
AK Scientific
SYN5725
https://aksci.com/item_detail.php?cat=SYN5725
AOBIOUS INC
AOB87385
http://aobious.com/aobious/search?search_query=AOB87385
Aceschem
ACS019978
https://www.aceschem.com/catalog/search.do?q=ACS019978
ApexBio Technology
B3553
https://www.apexbt.com/catalogsearch/result/?q=B3553
AstaTech
91452
http://astatechinc.com/CPSResult.php?CRNO=91452
BLD Pharm
BD399082
http://www.bldpharm.com/search/Search.html?keyword=BD399082
Capot Chemical
34087
https://www.capotchem.com/search.do?q=34087
Cayman Chemical
17653
http://www.caymanchem.com/app/template/Product.vm/catalog/17653
Chem Scene
CS-2791
http://www.chemscene.com/goproductList/searchProductList?productObj=CS-2791
ChemShuttle
136524
https://www.chemshuttle.com/catalogsearch/result/?q=136524
Debye Scientific
DA-36929
https://www.debyesci.com/index.php?id=product&ext[cno]=DA-36929
Excenen
EX-A1120
http://www.excenen.com/searchresultlist.php?id=EX-A1120
Hairui
HR33128
http://www.hairuichem.com/en/product/search.do?q=HR33128
KeyOrganics
AS-17026
http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17026
MedChem Express
HY-15968
https://www.medchemexpress.com/search.html?q=HY-15968&ft=&fa=&fp=
MolPort
MolPort-035-395-879
https://www.molport.com/shop/molecule-link/MolPort-035-395-879
Molcore
MC443093
http://www.molcore.com/CatMC443093.html
MuseChem
I000901
https://www.musechem.com/product/I000901.html
Selleck Chemicals
S7523
http://www.selleckchem.com/search.html?searchDTO.searchParam=S7523
ShangHai Biochempartner
BCP001143
http://www.biochempartner.com/search_BCP001143
ShangHai Biochempartner
BCP09582
http://www.biochempartner.com/search_BCP09582
eMolecules
49839446
https://orderbb.emolecules.com/search/#?query=49839446
eNovation Chemicals
D409773
https://www.enovationchem.com/Products.asp?SEARCHTEXT=D409773&searchbtn.x=0&searchbtn.y=0
mcule
MCULE-2016479441
https://mcule.com/MCULE-2016479441/
PubMed

PubMed

TitleDatePubMed
Discovery of GS-9973, a selective and orally efficacious inhibitor of spleen tyrosine kinase.
2014 May 8
Diffuse large B-cell lymphoma patient-derived xenograft models capture the molecular and biological heterogeneity of the disease.
2016 May 5
Patents

Patents

20100222323
3
20120220582
3
20130237520
3
20130237521
3

Sample Use Guides

In Vivo Use Guide
800 mg twice daily
Route of Administration: Oral
In Vitro Use Guide
Complete Mcl-1 downregulation was consistently achieved only with SYK inhibitor entospletinib (2h with 1uM of GS-9973).
Substance Class Chemical
Created
by admin
on Sat Dec 16 09:40:27 GMT 2023
Edited
by admin
on Sat Dec 16 09:40:27 GMT 2023
Record UNII
5H88K2AQ3R
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ENTOSPLETINIB DIMESYLATE HEMIHYDRATE
Common Name English
IMIDAZO(1,2-A)PYRAZIN-8-AMINE, 6-(1H-INDAZOL-6-YL)-N-(4-(4-MORPHOLINYL)PHENYL)-, METHANESULFONATE, HYDRATE (2:4:1)
Systematic Name English
Code System Code Type Description
CAS
1648797-47-0
Created by admin on Sat Dec 16 09:40:27 GMT 2023 , Edited by admin on Sat Dec 16 09:40:27 GMT 2023
PRIMARY
PUBCHEM
123133449
Created by admin on Sat Dec 16 09:40:27 GMT 2023 , Edited by admin on Sat Dec 16 09:40:27 GMT 2023
PRIMARY
FDA UNII
5H88K2AQ3R
Created by admin on Sat Dec 16 09:40:27 GMT 2023 , Edited by admin on Sat Dec 16 09:40:27 GMT 2023
PRIMARY
Related Record Type Details
Structure of ENTOSPLETINIB
PARENT -> SALT/SOLVATE
Structure of ENTOSPLETINIB DIMESYLATE
ANHYDROUS->SOLVATE
Related Record Type Details
Structure of ENTOSPLETINIB
ACTIVE MOIETY
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