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
3,4-Dihydroquinolin-2(1H)-ones as combined inhibitors of thromboxane A2 synthase and cAMP phosphodiesterase.	1992 Feb 21	1311763
Diagnosis and treatment of thrombocythemia in myeloproliferative disorders.	2001 Aug	11548978
Unexplained pulmonary hypertension in chronic myeloproliferative disorders.	2001 Sep	11555513
[Treatment of essential thrombocythemia with anagrelide: a ten-year experience].	2002	12150005
What is the standard treatment in essential thrombocythemia.	2002 Aug	12430943
Essential thrombocythemia: diagnosis and treatment, with special emphasis on the use of anagrelide.	2002 Jun	12243981
Variation of PDGF, TGFbeta, and bFGF levels in essential thrombocythemia patients treated with anagrelide.	2002 Jun	12111780
Cost-effectiveness considerations in the treatment of essential thrombocythemia.	2002 Jun	12096355
Other secondary sequelae of treatments for myeloproliferative disorders.	2002 Jun	12096354
Therapeutic options for essential thrombocythemia and polycythemia vera.	2002 Jun	12096352
Effects of anagrelide on in vivo megakaryocyte proliferation and maturation in essential thrombocythemia.	2002 Mar 1	11861274
Portal vein thrombosis after laparoscopy-assisted splenectomy and cholecystectomy.	2003 Apr	12677588
Indications for lowering platelet numbers in essential thrombocythemia.	2003 Jan	12682878
Pilot study of pegylated interferon-alpha 2b in patients with essential thrombocythemia.	2003 Jan	12497210
Essential thrombocytosis: diagnostic and treatment dilemmas.	2003 Nov-Dec	14750750
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	12949887
Thrombocytosis in an infant with high thrombopoietin concentrations.	2004 Feb	14767209
Thrombocytosis.	2004 Jun 10	15190151
A long-term study of young patients with essential thrombocythemia treated with anagrelide.	2004 Nov	15531452
Anagrelide therapy in pregnancy: report of a case of essential thrombocythemia.	2004 Nov	15278298
Anagrelide treatment in 52 patients with chronic myeloproliferative diseases.	2004 Oct	15485463
Moyamoya syndrome in an adolescent with essential thrombocythemia: successful intracranial carotid stent placement.	2005 Aug	16020757
High-output heart failure associated with anagrelide therapy for essential thrombocytosis.	2005 Aug 16	16103481
[Treatment of essential thrombocythemia].	2005 Dec	16122842
Anagrelide is effective in treating patients with hydroxyurea-resistant thrombocytosis in patients with chronic myeloid leukemia.	2005 Jan	15510207
Myeloproliferative disorders.	2005 Jul-Aug	16138485
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Management of patients with polycythaemia vera: results of a survey among Swedish haematologists.	2005 Jun	15876252
Anagrelide: analysis of long-term efficacy, safety and leukemogenic potential in myeloproliferative disorders.	2005 May	15755500
Anagrelide does not exert a myelodysplastic effect on megakaryopoiesis: a comparative immunohistochemical and morphometric study with hydroxyurea.	2005 Oct	16136489
Comparison of the biological activities of anagrelide and its major metabolites in haematopoietic cell cultures.	2005 Oct	16041400
Treatment of symptomatic patients with essential thrombocythemia: effectiveness of anagrelide.	2005 Sep	16138352
Essential thrombocythemia: scientific advances and current practice.	2006 Mar	16456375

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