U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C10H7Cl2N3O
Molecular Weight 256.0883
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ANAGRELIDE

SMILES

c1cc2c(CN3CC(=NC3=N2)O)c(c1Cl)Cl

InChI

InChIKey=OTBXOEAOVRKTNQ-UHFFFAOYSA-N
InChI=1S/C10H7Cl2N3O/c11-6-1-2-7-5(9(6)12)3-15-4-8(16)14-10(15)13-7/h1-2H,3-4H2,(H,13,14,16)

HIDE SMILES / InChI

Molecular Formula C10H7Cl2N3O
Molecular Weight 256.0883
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://www.rxlist.com/agrylin-drug.htm | https://www.drugs.com/pro/anagrelide.html | https://www.ncbi.nlm.nih.gov/pubmed/20331456

Anagrelide is an orally active quinazinolone derivative that was originally developed as an antiplatelet drug. The drug inhibits cyclic nucleotide phosphodiesterase III (PDEIII) and phopholipase A2, which is thought to cause the side effects of vasodilation, positive inotropism, reduced platelet aggregation. However, significant inhibition of platelet aggregation is observed only at doses of anagrelide higher than those required to reduce platelet count. It is indicated for the treatment of patients with thrombocythemia, secondary to myeloproliferative disorders. Commonly reported side effects of anagrelide include: abdominal pain, dizziness, headache, nausea, and palpitations. Other side effects include: back pain, fever, tachycardia, vomiting, and anorexia. There is a single case report, which suggests that sucralfate may interfere with anagrelide absorption. Anagrelide is an inhibitor of cyclic AMP PDE III. The effects of medicinal products with similar properties such as inotropes milrinone, enoximone, amrinone, olprinone and cilostazol may be exacerbated by anagrelide.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
36.0 nM [IC50]
Target ID: Phopholipase A2
Target ID: P05177
Gene ID: 1544.0
Gene Symbol: CYP1A2
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
AGRYLIN

Approved Use

Anagrelide hydrochloride capsules are indicated for the treatment of patients with thrombocythemia, secondary to myeloproliferative disorders, to reduce the elevated platelet count and the risk of thrombosis and to ameliorate associated symptoms including thrombo-hemorrhagic events (see CLINICAL STUDIES, DOSAGE AND ADMINISTRATION).

Launch Date

8.582976E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
10.28 ng/mL
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ANAGRELIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
28.39 ng × h/mL
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ANAGRELIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.38 h
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ANAGRELIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
1.9 mg 1 times / day multiple, oral (mean)
Recommended
Dose: 1.9 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.9 mg, 1 times / day
Sources: Page: p.33
unhealthy, 58
n = 16
Health Status: unhealthy
Condition: Thrombocythemia
Age Group: 58
Sex: M+F
Population Size: 16
Sources: Page: p.33
Disc. AE: Dizziness postural, Palpitations...
AEs leading to
discontinuation/dose reduction:
Dizziness postural (6.25%)
Palpitations (12.5%)
Chest pain (6.25%)
Sinus tachycardia (6.25%)
Abdominal pain (6.25%)
Sources: Page: p.33
1 mg 2 times / day multiple, oral
Recommended
Dose: 1 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1 mg, 2 times / day
Sources: Page: p.4
unhealthy
n = 942
Health Status: unhealthy
Condition: Thrombocythemia
Population Size: 942
Sources: Page: p.4
Disc. AE: Headache, Diarrhea...
AEs leading to
discontinuation/dose reduction:
Headache
Diarrhea
Edema
Palpitations
Abdominal pain
Sources: Page: p.4
10 mg 1 times / day multiple, oral (total daily dose)
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Thrombocythemia
Sources: Page: p.1
Disc. AE: Cardiotoxicity, QT interval prolonged...
AEs leading to
discontinuation/dose reduction:
Cardiotoxicity
QT interval prolonged
Ventricular tachycardia
Pulmonary hypertension
Bleeding
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Palpitations 12.5%
Disc. AE
1.9 mg 1 times / day multiple, oral (mean)
Recommended
Dose: 1.9 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.9 mg, 1 times / day
Sources: Page: p.33
unhealthy, 58
n = 16
Health Status: unhealthy
Condition: Thrombocythemia
Age Group: 58
Sex: M+F
Population Size: 16
Sources: Page: p.33
Abdominal pain 6.25%
Disc. AE
1.9 mg 1 times / day multiple, oral (mean)
Recommended
Dose: 1.9 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.9 mg, 1 times / day
Sources: Page: p.33
unhealthy, 58
n = 16
Health Status: unhealthy
Condition: Thrombocythemia
Age Group: 58
Sex: M+F
Population Size: 16
Sources: Page: p.33
Chest pain 6.25%
Disc. AE
1.9 mg 1 times / day multiple, oral (mean)
Recommended
Dose: 1.9 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.9 mg, 1 times / day
Sources: Page: p.33
unhealthy, 58
n = 16
Health Status: unhealthy
Condition: Thrombocythemia
Age Group: 58
Sex: M+F
Population Size: 16
Sources: Page: p.33
Dizziness postural 6.25%
Disc. AE
1.9 mg 1 times / day multiple, oral (mean)
Recommended
Dose: 1.9 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.9 mg, 1 times / day
Sources: Page: p.33
unhealthy, 58
n = 16
Health Status: unhealthy
Condition: Thrombocythemia
Age Group: 58
Sex: M+F
Population Size: 16
Sources: Page: p.33
Sinus tachycardia 6.25%
Disc. AE
1.9 mg 1 times / day multiple, oral (mean)
Recommended
Dose: 1.9 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.9 mg, 1 times / day
Sources: Page: p.33
unhealthy, 58
n = 16
Health Status: unhealthy
Condition: Thrombocythemia
Age Group: 58
Sex: M+F
Population Size: 16
Sources: Page: p.33
Abdominal pain Disc. AE
1 mg 2 times / day multiple, oral
Recommended
Dose: 1 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1 mg, 2 times / day
Sources: Page: p.4
unhealthy
n = 942
Health Status: unhealthy
Condition: Thrombocythemia
Population Size: 942
Sources: Page: p.4
Diarrhea Disc. AE
1 mg 2 times / day multiple, oral
Recommended
Dose: 1 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1 mg, 2 times / day
Sources: Page: p.4
unhealthy
n = 942
Health Status: unhealthy
Condition: Thrombocythemia
Population Size: 942
Sources: Page: p.4
Edema Disc. AE
1 mg 2 times / day multiple, oral
Recommended
Dose: 1 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1 mg, 2 times / day
Sources: Page: p.4
unhealthy
n = 942
Health Status: unhealthy
Condition: Thrombocythemia
Population Size: 942
Sources: Page: p.4
Headache Disc. AE
1 mg 2 times / day multiple, oral
Recommended
Dose: 1 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1 mg, 2 times / day
Sources: Page: p.4
unhealthy
n = 942
Health Status: unhealthy
Condition: Thrombocythemia
Population Size: 942
Sources: Page: p.4
Palpitations Disc. AE
1 mg 2 times / day multiple, oral
Recommended
Dose: 1 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1 mg, 2 times / day
Sources: Page: p.4
unhealthy
n = 942
Health Status: unhealthy
Condition: Thrombocythemia
Population Size: 942
Sources: Page: p.4
Bleeding Disc. AE
10 mg 1 times / day multiple, oral (total daily dose)
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Thrombocythemia
Sources: Page: p.1
Cardiotoxicity Disc. AE
10 mg 1 times / day multiple, oral (total daily dose)
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Thrombocythemia
Sources: Page: p.1
Pulmonary hypertension Disc. AE
10 mg 1 times / day multiple, oral (total daily dose)
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Thrombocythemia
Sources: Page: p.1
QT interval prolonged Disc. AE
10 mg 1 times / day multiple, oral (total daily dose)
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Thrombocythemia
Sources: Page: p.1
Ventricular tachycardia Disc. AE
10 mg 1 times / day multiple, oral (total daily dose)
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Thrombocythemia
Sources: Page: p.1
PubMed

PubMed

TitleDatePubMed
New approaches to the treatment of thrombocytosis.
2003 Feb
Management of the myeloproliferative disorders : distinguishing data from dogma.
2004
Treatment paradigms in the management of myeloproliferative disorders.
2004 Apr
The leukemia controversy in myeloproliferative disorders: is it a natural progression of disease, a secondary sequela of therapy, or a combination of both?
2004 Apr
Anagrelide: an update on its mechanisms of action and therapeutic potential.
2004 Aug
Anagrelide: a decade of clinical experience with its use for the treatment of primary thrombocythaemia.
2004 Aug
[Anagrelide in the treatment of thrombocythemia essential (ET)].
2004 Dec
[Diagnostic and therapeutic management of essential thrombocythemia in children].
2004 Jul-Sep
Thrombocytosis.
2004 Jun 10
Essential thrombocythaemia in children: is a treatment needed?
2004 May
Adverse effects and benefits of two years of anagrelide treatment for thrombocythemia in chronic myeloproliferative disorders.
2004 May
Essential thrombocythemia-related acute ST-segment elevation myocardial infarction. A case report and literature review.
2004 May-Jun
Anagrelide-associated cardiomyopathy in polycythemia vera and essential thrombocythemia.
2004 Nov
A long-term study of young patients with essential thrombocythemia treated with anagrelide.
2004 Nov
[Unclear liver fibrosis in a 42-year-old patient with polycythemia vera].
2004 Nov
Anagrelide therapy in pregnancy: report of a case of essential thrombocythemia.
2004 Nov
Anagrelide for thrombocytosis in myeloproliferative disorders: a prospective study to assess efficacy and adverse event profile.
2004 Nov 15
[Retrospective analysis of the clinical course of 12 children given the diagnosis essential thrombocythemia].
2004 Nov-Dec
Anagrelide treatment in 52 patients with chronic myeloproliferative diseases.
2004 Oct
Effects of anagrelide on platelet factor 4 and vascular endothelial growth factor levels in patients with essential thrombocythemia.
2004 Sep
Anagrelide-induced visual hallucinations in a patient with essential thrombocythemia.
2004 Sep
Current treatment of myelofibrosis.
2005 Apr
Primary and secondary thrombocytosis in childhood.
2005 Apr
Moyamoya syndrome in an adolescent with essential thrombocythemia: successful intracranial carotid stent placement.
2005 Aug
High-output heart failure associated with anagrelide therapy for essential thrombocytosis.
2005 Aug 16
High-performance liquid chromatography-mass spectrometry method for determination of anagrelide in human plasma.
2005 Aug 5
[Treatment of essential thrombocythemia].
2005 Dec
Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study.
2005 Dec 3
PDGF-A, PDGF-B, TGFbeta, and bFGF mRNA levels in patients with essential thrombocythemia treated with anagrelide.
2005 Feb
Anagrelide is effective in treating patients with hydroxyurea-resistant thrombocytosis in patients with chronic myeloid leukemia.
2005 Jan
When and how to treat essential thrombocythemia.
2005 Jul 7
Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia.
2005 Jul 7
Myeloproliferative disorders.
2005 Jul-Aug
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Management of patients with polycythaemia vera: results of a survey among Swedish haematologists.
2005 Jun
A critical review of anagrelide therapy in essential thrombocythemia and related disorders.
2005 May
Anagrelide: analysis of long-term efficacy, safety and leukemogenic potential in myeloproliferative disorders.
2005 May
Renal tubular injury associated with anagrelide use.
2005 May
Essential thrombocythemia.
2005 Oct
Anagrelide does not exert a myelodysplastic effect on megakaryopoiesis: a comparative immunohistochemical and morphometric study with hydroxyurea.
2005 Oct
Comparison of the biological activities of anagrelide and its major metabolites in haematopoietic cell cultures.
2005 Oct
Successful outcome with anagrelide in pregnancy.
2005 Oct
Treatment of symptomatic patients with essential thrombocythemia: effectiveness of anagrelide.
2005 Sep
Risk-adapted therapy in essential thrombocythemia and polycythemia vera.
2005 Sep
Anagrelide: a review of its use in the management of essential thrombocythaemia.
2006
Bilateral adrenal hemorrhage associated with essential thrombocytosis.
2006 Feb
'Double hit' from streptococcal pneumonia and hypersensitivity pneumonitis associated with anagrelide.
2006 Feb
A preliminary investigation into the action of anagrelide: thrombopoietin-c-Mpl receptor interactions.
2006 Jan
Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia.
2006 Jun 1
Essential thrombocythemia: scientific advances and current practice.
2006 Mar
Patents

Sample Use Guides

0.5 mg qid or 1 mg bid (2 capsules of 0.5 mg twice a day) for at least one week
Route of Administration: Oral
In Vitro Use Guide
Anagrelide was studied as an inhibitor of PDE fractions I, II and III separated from each other from rabbit heart supernatant. Anagrelide did not inhibit PDE I or II except at a concentration of 10(-4) M where inhibition of 33 and 39%, respectively, was noted. As expected, anagrelide inhibited PDE fraction III with a dose-response curve that was closely similar to that seen in the human platelet preparation. The IC50 for inhibition of the rabbit heart PDE fraction III was 7 x 10(-8) M.
Substance Class Chemical
Created
by admin
on Sat Jun 26 06:22:47 UTC 2021
Edited
by admin
on Sat Jun 26 06:22:47 UTC 2021
Record UNII
K9X45X0051
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ANAGRELIDE
EMA EPAR   HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
ANAGRELIDE [HSDB]
Common Name English
ANAGRELIDE [INN]
Common Name English
ANAGRELIDE [EMA EPAR]
Common Name English
6,7-DICHLORO-1,5-DIHYDROIMIDAZO(2,1-B)-QUINAZOLIN-2(3H)-ONE MONOHYDROCHLORIDE
Systematic Name English
ANAGRELIDE [VANDF]
Common Name English
ANAGRELIDE [WHO-DD]
Common Name English
IMIDAZO(2,1-B)QUINAZOLIN-2(3H)-ONE, 6,7-DICHLORO-1,5-DIHYDRO-, MONOHYDROCHLORIDE
Common Name English
ANAGRELIDE [MI]
Common Name English
Classification Tree Code System Code
LIVERTOX 54
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
FDA ORPHAN DRUG 14586
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
NDF-RT N0000175972
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
FDA ORPHAN DRUG 20887
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
FDA ORPHAN DRUG 6985
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
WHO-VATC QL01XX35
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
NCI_THESAURUS C1327
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
NDF-RT N0000175638
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
WHO-ATC L01XX35
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
Code System Code Type Description
EPA CompTox
68475-42-3
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
PRIMARY
NCI_THESAURUS
C28825
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
PRIMARY
DRUG CENTRAL
209
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
PRIMARY
EVMPD
SUB05499MIG
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
PRIMARY
CAS
68475-42-3
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
PRIMARY
MERCK INDEX
M1886
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
PRIMARY Merck Index
IUPHAR
7114
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
PRIMARY
ChEMBL
CHEMBL760
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
PRIMARY
FDA UNII
K9X45X0051
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
PRIMARY
WIKIPEDIA
ANAGRELIDE
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
PRIMARY
PUBCHEM
135409400
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
PRIMARY
LACTMED
Anagrelide
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
PRIMARY
RXCUI
596724
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
PRIMARY RxNorm
HSDB
7325
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
PRIMARY
DRUG BANK
DB00261
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
PRIMARY
INN
4672
Created by admin on Sat Jun 26 06:22:47 UTC 2021 , Edited by admin on Sat Jun 26 06:22:47 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
OFF-TARGET->INHIBITOR
IC50
SALT/SOLVATE -> PARENT
EXCRETED UNCHANGED
URINE
SALT/SOLVATE -> PARENT
Related Record Type Details
METABOLITE INACTIVE -> PARENT
METABOLITE ACTIVE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC