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Details

Stereochemistry ACHIRAL
Molecular Formula C10H7Cl2N3O
Molecular Weight 256.088
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ANAGRELIDE

SMILES

ClC1=CC=C2NC3=NC(=O)CN3CC2=C1Cl

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

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
3,4-Dihydroquinolin-2(1H)-ones as combined inhibitors of thromboxane A2 synthase and cAMP phosphodiesterase.
1992 Feb 21
Essential thrombocythemia (ET): moving from palliation to cure.
2002 Dec
Comparison of the pharmacological mechanisms involved in the platelet lowering actions of anagrelide and hydroxyurea: a review.
2002 Nov
[Anagrelide-induced changes of megakaryopoiesis during therapy of chronic myeloproliferative disorders with thrombocythemia].
2002 Nov
Hematologic aspects of liver transplantation for Budd-Chiari syndrome with special reference to myeloproliferative disorders.
2002 Oct 27
Associated thrombophilic defects in essential thrombocythaemia: their relationship with clinical manifestations.
2003
Portal vein thrombosis after laparoscopy-assisted splenectomy and cholecystectomy.
2003 Apr
[Ulcers on the legs and feet: a seldom recognised side effect of hydroxyurea].
2003 Aug 2
[Recurring ischemic cerebral infarction caused by primary thrombocytosis in infancy].
2003 Dec 1-15
New approaches to the treatment of thrombocytosis.
2003 Feb
Modern treatment strategies in polycythemia vera.
2003 Jan
Indications for lowering platelet numbers in essential thrombocythemia.
2003 Jan
Pilot study of pegylated interferon-alpha 2b in patients with essential thrombocythemia.
2003 Jan
Essential thrombocytosis: diagnostic and treatment dilemmas.
2003 Nov-Dec
Anagrelide-induced bone marrow changes during therapy of chronic myeloproliferative disorders with thrombocytosis. an immunohistochemical and morphometric study of sequential trephine biopsies.
2003 Oct
Acute leukemia and myelodysplasia in patients with a Philadelphia chromosome negative chronic myeloproliferative disorder treated with hydroxyurea alone or with hydroxyurea after busulphan.
2003 Sep
Pharmacotherapy of essential thrombocythaemia: economic considerations.
2003 Sep
Anagrelide and imatinib mesylate combination therapy in patients with chronic myeloproliferative disorders.
2003 Sep
Management of the myeloproliferative disorders : distinguishing data from dogma.
2004
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: a decade of clinical experience with its use for the treatment of primary thrombocythaemia.
2004 Aug
Thrombocytosis in an infant with high thrombopoietin concentrations.
2004 Feb
Thalidomide for the treatment of idiopathic myelofibrosis.
2004 Jan
[Diagnostic and therapeutic management of essential thrombocythemia in children].
2004 Jul-Sep
Thrombocytosis.
2004 Mar 18
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
[Unclear liver fibrosis in a 42-year-old patient with polycythemia vera].
2004 Nov
Anagrelide for thrombocytosis in myeloproliferative disorders: a prospective study to assess efficacy and adverse event profile.
2004 Nov 15
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
Current treatment of myelofibrosis.
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
PDGF-A, PDGF-B, TGFbeta, and bFGF mRNA levels in patients with essential thrombocythemia treated with anagrelide.
2005 Feb
When and how to treat essential thrombocythemia.
2005 Jul 7
Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia.
2005 Jul 7
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
Essential thrombocythemia.
2005 Oct
Comparison of the biological activities of anagrelide and its major metabolites in haematopoietic cell cultures.
2005 Oct
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.
Name Type Language
ANAGRELIDE
EMA EPAR   HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
ANAGRELIDE [HSDB]
Common Name English
Anagrelide [WHO-DD]
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
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
FDA ORPHAN DRUG 935223
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
LIVERTOX NBK548467
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
FDA ORPHAN DRUG 14586
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
NDF-RT N0000175972
Created by admin on Wed Jul 05 23:19:38 UTC 2023 , Edited by admin on Wed Jul 05 23:19:38 UTC 2023
FDA ORPHAN DRUG 20887
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
FDA ORPHAN DRUG 6985
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
WHO-VATC QL01XX35
Created by admin on Wed Jul 05 23:19:38 UTC 2023 , Edited by admin on Wed Jul 05 23:19:38 UTC 2023
NCI_THESAURUS C1327
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
NDF-RT N0000175638
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
WHO-ATC L01XX35
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
Code System Code Type Description
EPA CompTox
DTXSID4048305
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
PRIMARY
CHEBI
142290
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
PRIMARY
NCI_THESAURUS
C28825
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
PRIMARY
DRUG CENTRAL
209
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
PRIMARY
EVMPD
SUB05499MIG
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
PRIMARY
CAS
68475-42-3
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
PRIMARY
MERCK INDEX
M1886
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
PRIMARY Merck Index
IUPHAR
7114
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
PRIMARY
ChEMBL
CHEMBL760
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
PRIMARY
FDA UNII
K9X45X0051
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
PRIMARY
CHEBI
55345
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
PRIMARY
WIKIPEDIA
ANAGRELIDE
Created by admin on Wed Jul 05 23:19:38 UTC 2023 , Edited by admin on Wed Jul 05 23:19:38 UTC 2023
PRIMARY
SMS_ID
100000085241
Created by admin on Wed Jul 05 23:19:38 UTC 2023 , Edited by admin on Wed Jul 05 23:19:38 UTC 2023
PRIMARY
PUBCHEM
135409400
Created by admin on Wed Jul 05 23:19:38 UTC 2023 , Edited by admin on Wed Jul 05 23:19:38 UTC 2023
PRIMARY
LACTMED
Anagrelide
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
PRIMARY
RXCUI
596724
Created by admin on Wed Jul 05 23:19:38 UTC 2023 , Edited by admin on Wed Jul 05 23:19:38 UTC 2023
PRIMARY RxNorm
DAILYMED
K9X45X0051
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
PRIMARY
HSDB
7325
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
PRIMARY
DRUG BANK
DB00261
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
PRIMARY
INN
4672
Created by admin on Wed Jul 05 23:19:37 UTC 2023 , Edited by admin on Wed Jul 05 23:19:37 UTC 2023
PRIMARY