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
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)
Molecular Formula | C10H7Cl2N3O |
Molecular Weight | 256.088 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator'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
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2094125 |
36.0 nM [IC50] | ||
Target ID: Phopholipase A2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20331456 |
|||
Target ID: P05177 Gene ID: 1544.0 Gene Symbol: CYP1A2 Target Organism: Homo sapiens (Human) |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | AGRYLIN Approved UseAnagrelide 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 Date1997 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
10.28 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19302911 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
28.39 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19302911 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.38 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19302911 |
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
Dose | Population | Adverse 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%) Sources: Page: p.33Palpitations (12.5%) Chest pain (6.25%) Sinus tachycardia (6.25%) Abdominal pain (6.25%) |
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 Sources: Page: p.4Diarrhea Edema Palpitations Abdominal pain |
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 Sources: Page: p.1QT interval prolonged Ventricular tachycardia Pulmonary hypertension Bleeding |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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
Title | Date | PubMed |
---|---|---|
3,4-Dihydroquinolin-2(1H)-ones as combined inhibitors of thromboxane A2 synthase and cAMP phosphodiesterase. | 1992 Feb 21 |
|
Current management in polycythemia vera. | 2001 Jan |
|
The diagnosis and management of polycythemia vera in the era since the Polycythemia Vera Study Group: a survey of American Society of Hematology members' practice patterns. | 2002 Feb 15 |
|
Chronic myeloid leukaemia with marked thrombocytosis in a patient with thalassaemia major: complete haematological remission under the combination of hydroxyurea and anagrelide. | 2002 Jan |
|
Is the platelet lowering activity of anagrelide mediated by its major metabolite 2-amino-5,6-dichloro-3,4-dihydroquinazoline (RL603)? | 2002 Jul |
|
Essential thrombocythemia: diagnosis and treatment, with special emphasis on the use of anagrelide. | 2002 Jun |
|
Therapeutic options for essential thrombocythemia and polycythemia vera. | 2002 Jun |
|
New approaches to the treatment of thrombocytosis. | 2003 Feb |
|
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 |
|
Management of the myeloproliferative disorders : distinguishing data from dogma. | 2004 |
|
[Anagrelide in the treatment of thrombocythemia essential (ET)]. | 2004 Dec |
|
Thalidomide for the treatment of idiopathic myelofibrosis. | 2004 Jan |
|
[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 |
|
[Unclear liver fibrosis in a 42-year-old patient with polycythemia vera]. | 2004 Nov |
|
Moyamoya syndrome in an adolescent with essential thrombocythemia: successful intracranial carotid stent placement. | 2005 Aug |
|
[Treatment of essential thrombocythemia]. | 2005 Dec |
|
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 |
|
Successful outcome with anagrelide in pregnancy. | 2005 Oct |
|
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 |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2456068
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
Edited
Fri Dec 15 15:51:16 GMT 2023
by
admin
on
Fri Dec 15 15:51:16 GMT 2023
|
Record UNII |
K9X45X0051
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
FDA ORPHAN DRUG |
935223
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
||
|
LIVERTOX |
NBK548467
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
||
|
FDA ORPHAN DRUG |
14586
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
||
|
NDF-RT |
N0000175972
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
||
|
FDA ORPHAN DRUG |
20887
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
||
|
FDA ORPHAN DRUG |
6985
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
||
|
WHO-VATC |
QL01XX35
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
||
|
NCI_THESAURUS |
C1327
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
||
|
NDF-RT |
N0000175638
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
||
|
WHO-ATC |
L01XX35
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
DTXSID4048305
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | |||
|
142290
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | |||
|
C28825
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | |||
|
209
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | |||
|
SUB05499MIG
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | |||
|
68475-42-3
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | |||
|
m1886
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | Merck Index | ||
|
7114
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | |||
|
CHEMBL760
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | |||
|
K9X45X0051
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | |||
|
55345
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | |||
|
ANAGRELIDE
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | |||
|
100000085241
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | |||
|
135409400
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | |||
|
Anagrelide
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | |||
|
596724
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | RxNorm | ||
|
K9X45X0051
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | |||
|
7325
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | |||
|
DB00261
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
PRIMARY | |||
|
4672
Created by
admin on Fri Dec 15 15:51:16 GMT 2023 , Edited by admin on Fri Dec 15 15:51:16 GMT 2023
|
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 |
|
|
|||