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anagrelide 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| platelet aggregation inhibitors | 209 | 68475-42-3 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
imidazoquinazoline derivative which lowers platelet count probably by inhibiting thrombopoiesis and reduces platelet aggregation; used for thrombocythemia
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
None
ADMET properties:
| Property | Value | Reference |
|---|---|---|
| MRTD (Maximum Recommended Therapeutic Daily Dose) | 0.56 µM/kg/day | Contrera JF, Matthews EJ, Kruhlak NL, Benz RD |
| BA (Bioavailability) | 75 % | Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H |
| BDDCS (Biopharmaceutical Drug Disposition Classification System) | 2 | Bocci G, Oprea TI, Benet LZ |
Predicted pharmacokinetic/toxicological properties (PK-AZ):
| Property | Description | Value | Unit | Confidence | Similarity |
|---|---|---|---|---|---|
| azlogd74 | LogD at pH 7.4 | 2.127 | High | 1 | |
| caco2-efflux | Caco-2 efflux ratio (BA/AB) | 1.346 | High | 1 | |
| caco2-intrinsic-papp | Caco-2 intrinsic apparent permeability | 46.774 | 10^-6 cm/s | High | 1 |
| dh-clint | Dog hepatocyte intrinsic clearance | 9.120 | uL/min/10^6 cells | High | 1 |
| dppb | Dog plasma protein binding (% unbound) | 10.510 | % | High | 1 |
| fcs-ppb | Fetal calf serum protein binding (% unbound) | 19.200 | % | High | 1 |
| herg | hERG pIC50 | 4.514 | pIC50 | High | 1 |
| hh-clint | Human hepatocyte intrinsic clearance | 1.901 | uL/min/10^6 cells | High | 1 |
| hlm-clint | Human liver microsomal intrinsic clearance | 7.603 | uL/min/mg protein | High | 1 |
| hppb | Human plasma protein binding (% unbound) | 10.710 | % | High | 1 |
| kinase-safety-class | ACVR2B,AXL,BRAF,CAMK2B,CAMK2D,CDK5,CDK9,DYRK1B,EIF2AK3,ERBB2,GRK2,ITK,MAP3K21,MAPK7,PDK1,PDK2,PDK4,PIK3CB,PIK3CD,PIK3CG,PRKDC,STK33 | 22 | |||
| kinase-selectivity-class | ACVR2B,AXL,CDK9,EIF2AK3,GRK2,GSK3A,MAP2K6,MAPK7,PIK3CB | 9 | |||
| mdck-mdr1-efflux | MDCK-MDR1 efflux ratio | 7.096 | High | 1 | |
| mh-clint | Mouse hepatocyte intrinsic clearance | 17.947 | High | 1 | |
| mppb | Mouse plasma protein binding (% unbound) | 15.430 | High | 1 | |
| nih-mdck-mdr1-efflux | NIH MDCK-MDR1 efflux ratio | 4.667 | High | 1 | |
| pfas-class | PFAS structural alert (1 = True, 0 = False) | 0 | |||
| pppb | Pig plasma protein binding (% unbound) | 13.120 | % | High | 1 |
| rh-clint | Rat hepatocyte intrinsic clearance | 5.559 | uL/min/10^6 cells | High | 1 |
| rh-fuinc | Rat hepatocyte fraction unbound in incubation | 81.710 | % | High | 1 |
| rppb | Rat plasma protein binding (% unbound) | 15.820 | % | High | 1 |
| solubility-dd | Solubility at pH 7.4 in DMSO | 51.880 | uM | High | 1 |
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| Nov. 15, 2004 | EMA | SHIRE PHARMACEUTICALS IRELAND LIMITED | |
| March 14, 1997 | FDA | SHIRE LLC |
FDA Adverse Event Reporting System (Female)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Platelet count increased | 114.19 | 29.97 | 33 | 1660 | 20826 | 90605928 |
| Myelofibrosis | 110.68 | 29.97 | 20 | 1673 | 1547 | 90625207 |
| Angiodermatitis | 93.39 | 29.97 | 13 | 1680 | 182 | 90626572 |
| Thrombocytosis | 46.97 | 29.97 | 13 | 1680 | 6988 | 90619766 |
| Skin ulcer | 45.39 | 29.97 | 21 | 1672 | 50054 | 90576700 |
| Bone marrow reticulin fibrosis | 37.93 | 29.97 | 6 | 1687 | 207 | 90626547 |
| Myeloproliferative neoplasm | 37.40 | 29.97 | 7 | 1686 | 655 | 90626099 |
| Pyelonephritis | 36.29 | 29.97 | 14 | 1679 | 21302 | 90605452 |
| Anaemia | 35.46 | 29.97 | 38 | 1655 | 352764 | 90273990 |
| Prinzmetal angina | 34.21 | 29.97 | 7 | 1686 | 1038 | 90625716 |
| Dementia | 31.34 | 29.97 | 13 | 1680 | 23848 | 90602906 |
| Ventricular tachyarrhythmia | 30.74 | 29.97 | 5 | 1688 | 206 | 90626548 |
| Adenocarcinoma metastatic | 30.29 | 29.97 | 5 | 1688 | 226 | 90626528 |
FDA Adverse Event Reporting System (Male)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Platelet count increased | 50.52 | 32.69 | 16 | 1005 | 10687 | 42609627 |
| Myelofibrosis | 33.66 | 32.69 | 8 | 1013 | 1839 | 42618475 |
FDA Adverse Event Reporting System (Geriatric)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Platelet count increased | 136.52 | 27.27 | 42 | 2530 | 26292 | 110560435 |
| Myelofibrosis | 98.65 | 27.27 | 21 | 2551 | 3030 | 110583697 |
| Angiodermatitis | 90.14 | 27.27 | 13 | 2559 | 188 | 110586539 |
| Thrombocytosis | 59.80 | 27.27 | 18 | 2554 | 10426 | 110576301 |
| Skin ulcer | 50.11 | 27.27 | 26 | 2546 | 63619 | 110523108 |
| Acute myocardial infarction | 43.43 | 27.27 | 26 | 2546 | 83751 | 110502976 |
| Cerebral infarction | 43.18 | 27.27 | 22 | 2550 | 51816 | 110534911 |
| Prinzmetal angina | 42.52 | 27.27 | 10 | 2562 | 2259 | 110584468 |
| Myeloproliferative neoplasm | 41.61 | 27.27 | 9 | 2563 | 1396 | 110585331 |
| Splenomegaly | 41.35 | 27.27 | 17 | 2555 | 24481 | 110562246 |
| Bone marrow reticulin fibrosis | 33.70 | 27.27 | 6 | 2566 | 340 | 110586387 |
| Congestive cardiomyopathy | 31.46 | 27.27 | 12 | 2560 | 14207 | 110572520 |
| Pyelonephritis | 31.02 | 27.27 | 14 | 2558 | 25236 | 110561491 |
| Cardiac failure | 30.41 | 27.27 | 29 | 2543 | 187597 | 110399130 |
| Anaemia | 28.70 | 27.27 | 48 | 2524 | 547038 | 110039689 |
| Pulmonary arterial hypertension | 27.63 | 27.27 | 14 | 2558 | 32554 | 110554173 |
FDA Adverse Event Reporting System (Pediatric)
None
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| ATC | L01XX35 | ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS OTHER ANTINEOPLASTIC AGENTS Other antineoplastic agents |
| FDA MoA | N0000175086 | Phosphodiesterase 3 Inhibitors |
| MeSH PA | D002317 | Cardiovascular Agents |
| MeSH PA | D005343 | Fibrinolytic Agents |
| MeSH PA | D006401 | Hematologic Agents |
| MeSH PA | D010975 | Platelet Aggregation Inhibitors |
| FDA EPC | N0000175638 | Platelet-reducing Agent |
| FDA PE | N0000175972 | Decreased Platelet Production |
| CHEBI has role | CHEBI:35610 | antineoplastic agent |
| CHEBI has role | CHEBI:48675 | antifibrinolytic drug |
| CHEBI has role | CHEBI:50249 | anticoagulant |
| CHEBI has role | CHEBI:50427 | platelet aggregation inhibitor |
| CHEBI has role | CHEBI:35554 | cardiovascular drug |
Related Drugs by ATC class:
L01XX Other antineoplastic agents 33 drugs
Drug Use | Suggest Off label Use Form| |View source of the data|
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| Essential thrombocythemia | indication | 109994006 | DOID:2224 |
| Thrombocytosis in Myeloproliferative Disease | indication | ||
| High output heart failure | contraindication | 10091002 | |
| Heart disease | contraindication | 56265001 | DOID:114 |
| Hepatic failure | contraindication | 59927004 | |
| Interstitial pneumonia | contraindication | 64667001 | |
| Blood coagulation disorder | contraindication | 64779008 | DOID:1247 |
| Kidney disease | contraindication | 90708001 | DOID:557 |
| Interstitial lung disease | contraindication | 233703007 | DOID:3082 |
| Disease of liver | contraindication | 235856003 | DOID:409 |
| Anemia | contraindication | 271737000 | DOID:2355 |
| Thrombocytopenic disorder | contraindication | 302215000 | DOID:1588 |
| Eosinophilic asthma | contraindication | 367542003 | DOID:9498 |
🐶 Veterinary Drug Use
None
🐶 Veterinary products
None
Acid dissociation constants calculated using MoKa v3.0.0
| Dissociation level | Dissociation constant | Type (acidic/basic) |
|---|---|---|
| pKa1 | 10.12 | acidic |
| pKa2 | 3.82 | Basic |
Orange Book patent data (new drug applications)
None
Orange Book exclusivity data (new drug applications)
None
Bioactivity Summary:
| Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA source |
|---|---|---|---|---|---|---|---|---|---|
| cGMP-inhibited 3',5'-cyclic phosphodiesterase A | Enzyme | INHIBITOR | IC50 | 7.27 | IUPHAR | CHEMBL | |||
| cGMP-dependent 3',5'-cyclic phosphodiesterase | Enzyme | IC50 | 4.47 | CHEMBL |
External reference:
| ID | Source |
|---|---|
| 4024077 | VUID |
| N0000022082 | NUI |
| D02933 | KEGG_DRUG |
| 823178-43-4 | SECONDARY_CAS_RN |
| 236612 | RXNORM |
| C0051809 | UMLSCUI |
| CHEBI:55345 | CHEBI |
| CHEMBL760 | ChEMBL_ID |
| CHEMBL1200759 | ChEMBL_ID |
| DB00261 | DRUGBANK_ID |
| C021139 | MESH_SUPPLEMENTAL_RECORD_UI |
| 135409400 | PUBCHEM_CID |
| 7114 | IUPHAR_LIGAND_ID |
| 4672 | INN_ID |
| K9X45X0051 | UNII |
| 4199 | MMSL |
| 58814 | MMSL |
| d04126 | MMSL |
| J33 | PDB_CHEM_ID |
| 4021052 | VANDF |
| 4024077 | VANDF |
| 006435 | NDDF |
| 006436 | NDDF |
| 1001001000202106 | SNOMEDCT_US |
| 108976008 | SNOMEDCT_US |
| 108977004 | SNOMEDCT_US |
| 372561005 | SNOMEDCT_US |
| K9X45X0051 | INXIGHT DRUGS |
Pharmaceutical products:
None