ANAGRELIDE

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 Search

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

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

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020333s017lbl.pdf
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	Potency
Phosphodiesterase 3 61 Target ID: CHEMBL2094125 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16041400 \| https://www.ncbi.nlm.nih.gov/pubmed/20331456 \| https://www.ncbi.nlm.nih.gov/pubmed/2456068	Inhibitor 8504	36.0 nM [IC50]
Phopholipase A2 3 Target ID: Phopholipase A2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20331456	Inhibitor 8504
Cytochrome P450 1A2 73 Target ID: P05177 Gene ID: 1544.0 Gene Symbol: CYP1A2 Target Organism: Homo sapiens (Human) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020333s017lbl.pdf	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Thrombocythemia 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020333s017lbl.pdf	Primary		Approved 8583	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 1997

C_max

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

T_1/2

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 Recommended Dose: 1.9 mg, 1 times / day Route: oral Route: multiple Dose: 1.9 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10200810	unhealthy, 58 Health Status: unhealthy Age Group: 58 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/10200810	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: https://pubmed.ncbi.nlm.nih.gov/10200810
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020333s024lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020333s024lbl.pdf	Disc. AE: Headache, Diarrhea... AEs leading to discontinuation/dose reduction: Headache Diarrhea Edema Palpitations Abdominal pain Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020333s024lbl.pdf
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020333s024lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020333s024lbl.pdf	Disc. AE: Cardiotoxicity, QT interval prolonged... AEs leading to discontinuation/dose reduction: Cardiotoxicity QT interval prolonged Ventricular tachycardia Pulmonary hypertension Bleeding Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020333s024lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 substrate 1946 inducer 1087	inhibitor 2438 substrate 1193	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2C19 2057	CYP1A2 1197 CYP1A1 389 CYP2C19 1119	CYP1A 59

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/020333s027lbl.pdf#page=7 \| https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=18 Page: 7, (PBDA) 18	likely
CYP1A 122	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=18 Page: 18.0	no
CYP1A 122	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=18 Page: 18.0	no	3-Hydroxy-anagrelide (BCH24426) 3
CYP1A2 2333	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=18 Page: 18.0	no	RL603 3
CYP2C19 2141	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=18 Page: 18.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=18 Page: 18.0	no	RL603 3
CYP2C9 2497	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=18 Page: 16.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=18 Page: 18.0	no	RL603 3
CYP2D6 2546	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=18 Page: 18.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=18 Page: 18.0	no	RL603 3
CYP3A4 2633	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=18 Page: 18.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=18 Page: 18.0	no	3-Hydroxy-anagrelide (BCH24426) 3
CYP3A4 2633	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=18 Page: 18.0	no	RL603 3
CYP3A4 2633	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=18 Page: 18.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=18 Page: 18.0	no	RL603 3
CYP1A2 2333	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=18 Page: 18.0	yes [IC50 26.8 uM]	3-Hydroxy-anagrelide (BCH24426) 3
CYP1A 122	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=18 Page: 18.0	yes	RL603 3

Drug as victim

Target	Modality	Activity	Metabolite
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/020333s027lbl.pdf#page=11 Page: 11.0	major
CYP2C19 1119	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=16 Page: 16.0	no
CYP2C9 1193	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=16 Page: 16.0	no
CYP2D6 1388	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=16 Page: 16.0	no
CYP3A4 1946	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=16 Page: 16.0	no
CYP1A1 389	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=16 Page: 16.0	yes	3-Hydroxy-anagrelide (BCH24426) 3
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/020333s027lbl.pdf#page=11 Page: 11.0	yes	3-Hydroxy-anagrelide 3

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=10 Page: 10.0
hERG 2263	inhibitor 2237 Sources: https://www.pmda.go.jp/drugs/2014/P201400120/342358000_22600AMX01305_A100_1.pdf#page=10 Page: 10.0		RL603 3

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:142290	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:142290
ChemicalBook	CB8246866	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8246866
eMolecules	2726176	https://www.emolecules.com/cgi-bin/more?vid=2726176
eMolecules	901387	https://www.emolecules.com/cgi-bin/more?vid=901387
MolPort	MolPort-003-844-624	https://www.molport.com/shop/molecule-link/MolPort-003-844-624
MolPort	MolPort-005-934-314	https://www.molport.com/shop/molecule-link/MolPort-005-934-314
ZINC	ZINC000003871541	http://zinc15.docking.org/substances/ZINC000003871541

PubMed

Title	Date	PubMed
Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia.	2006-06-01	16484586
Essential thrombocythemia: scientific advances and current practice.	2006-03	16456375
Bilateral adrenal hemorrhage associated with essential thrombocytosis.	2006-02	16432870
'Double hit' from streptococcal pneumonia and hypersensitivity pneumonitis associated with anagrelide.	2006-02	16430463
A preliminary investigation into the action of anagrelide: thrombopoietin-c-Mpl receptor interactions.	2006-01	16413395
Anagrelide: a review of its use in the management of essential thrombocythaemia.	2006	16398570
Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study.	2005-12-03	16325696
[Treatment of essential thrombocythemia].	2005-12	16122842
Essential thrombocythemia.	2005-10	16210036
Anagrelide does not exert a myelodysplastic effect on megakaryopoiesis: a comparative immunohistochemical and morphometric study with hydroxyurea.	2005-10	16136489
Comparison of the biological activities of anagrelide and its major metabolites in haematopoietic cell cultures.	2005-10	16041400
Successful outcome with anagrelide in pregnancy.	2005-10	15959777
Myeloproliferative disorders.	2005-09-06	16138485
Treatment of symptomatic patients with essential thrombocythemia: effectiveness of anagrelide.	2005-09	16138352
Risk-adapted therapy in essential thrombocythemia and polycythemia vera.	2005-09	15963833
High-output heart failure associated with anagrelide therapy for essential thrombocytosis.	2005-08-16	16103481
High-performance liquid chromatography-mass spectrometry method for determination of anagrelide in human plasma.	2005-08-05	16005692
Moyamoya syndrome in an adolescent with essential thrombocythemia: successful intracranial carotid stent placement.	2005-08	16020757
When and how to treat essential thrombocythemia.	2005-07-07	16000360
Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia.	2005-07-07	16000354
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005-06	15962942
Management of patients with polycythaemia vera: results of a survey among Swedish haematologists.	2005-06	15876252
A critical review of anagrelide therapy in essential thrombocythemia and related disorders.	2005-05	16019501
Anagrelide: analysis of long-term efficacy, safety and leukemogenic potential in myeloproliferative disorders.	2005-05	15755500
Renal tubular injury associated with anagrelide use.	2005-05	15728271
[Diagnostic and therapeutic management of essential thrombocythemia in children].	2005-04-29	15858255
Current treatment of myelofibrosis.	2005-04	16166999
Primary and secondary thrombocytosis in childhood.	2005-04	15813844
PDGF-A, PDGF-B, TGFbeta, and bFGF mRNA levels in patients with essential thrombocythemia treated with anagrelide.	2005-02	15682418
Anagrelide is effective in treating patients with hydroxyurea-resistant thrombocytosis in patients with chronic myeloid leukemia.	2005-01	15510207
[Anagrelide in the treatment of thrombocythemia essential (ET)].	2004-12	15962609
[Retrospective analysis of the clinical course of 12 children given the diagnosis essential thrombocythemia].	2004-11-27	15565550
Anagrelide for thrombocytosis in myeloproliferative disorders: a prospective study to assess efficacy and adverse event profile.	2004-11-15	15476273
Anagrelide-associated cardiomyopathy in polycythemia vera and essential thrombocythemia.	2004-11	15531464
A long-term study of young patients with essential thrombocythemia treated with anagrelide.	2004-11	15531452
[Unclear liver fibrosis in a 42-year-old patient with polycythemia vera].	2004-11	15372168
Anagrelide therapy in pregnancy: report of a case of essential thrombocythemia.	2004-11	15278298
Anagrelide treatment in 52 patients with chronic myeloproliferative diseases.	2004-10	15485463
Effects of anagrelide on platelet factor 4 and vascular endothelial growth factor levels in patients with essential thrombocythemia.	2004-09	15352995
Anagrelide-induced visual hallucinations in a patient with essential thrombocythemia.	2004-09	15287922
Anagrelide: an update on its mechanisms of action and therapeutic potential.	2004-08	15270658
Anagrelide: a decade of clinical experience with its use for the treatment of primary thrombocythaemia.	2004-08	15264993
Thrombocytosis.	2004-06-10	15190151
Essential thrombocythemia-related acute ST-segment elevation myocardial infarction. A case report and literature review.	2004-05-25	15156266
Essential thrombocythaemia in children: is a treatment needed?	2004-05	15155103
Adverse effects and benefits of two years of anagrelide treatment for thrombocythemia in chronic myeloproliferative disorders.	2004-05	15136214
Treatment paradigms in the management of myeloproliferative disorders.	2004-04	15190519
The leukemia controversy in myeloproliferative disorders: is it a natural progression of disease, a secondary sequela of therapy, or a combination of both?	2004-04	15190518
Management of the myeloproliferative disorders : distinguishing data from dogma.	2004	15190294
New approaches to the treatment of thrombocytosis.	2003-02	16224383

Patents

Sample Use Guides

In Vivo Use Guide

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 `Mon Mar 31 18:11:02 GMT 2025` Edited by `admin` on `Mon Mar 31 18:11:02 GMT 2025`
Record UNII	K9X45X0051
Record Status	`Validated (UNII)`
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Name

Type

Language

ANAGRELIDE

Official Name

English

ANAGRELIDE [EMA EPAR]

Preferred Name

English

ANAGRELIDE [HSDB]

Common Name

English

Anagrelide [WHO-DD]

Common Name

English

anagrelide [INN]

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