Identification

Name
Cangrelor
Accession Number
DB06441
Type
Small Molecule
Groups
Approved
Description

Cangrelor is an intravenous, direct-acting, reversible P2Y12 inhibitor for patients undergoing percutaneous coronary intervention (PCI) who have not been yet treated by oral P2Y12 inhibitors. An advantage Cangrelor provides over oral P2Y12 inhibitors (such as prasugrel, ticagrelor, and clopidogrel) is that it is an active drug not requiring metabolic conversion therefore providing a rapid onset and offset of action. Cangrelor was approved by the FDA in June 2015 for intravenous application.

Structure
Thumb
Synonyms
  • [dichloro-[[[(2R,3S,4R,5R)-3,4-dihydroxy-5-[6-(2-methylsulfanylethylamino)-2-(3,3,3-trifluoropropylsulfanyl)purin-9-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]methyl]phosphonic acid
External IDs
AR-C69931XX / AR69931
Product Ingredients
IngredientUNIICASInChI Key
Cangrelor tetrasodium2144G00Y7W163706-36-3COWWROCHWNGJHQ-OPKBHZIBSA-J
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
KengrealInjection, powder, lyophilized, for solution50 mg/1IntravenousChiesi Pharmaceuticals Inc.2015-07-08Not applicableUs
KengrealInjection, powder, lyophilized, for solution50 mg/1IntravenousThe Medicines Company2015-07-08Not applicableUs
KengrexalInjection, powder, for solution50 mgIntravenousChiesi Farmaceutici S.P.A.2015-03-23Not applicableEu
Categories
UNII
6AQ1Y404U7
CAS number
163706-06-7
Weight
Average: 776.35
Monoisotopic: 774.9483145
Chemical Formula
C17H25Cl2F3N5O12P3S2
InChI Key
PAEBIVWUMLRPSK-IDTAVKCVSA-N
InChI
InChI=1S/C17H25Cl2F3N5O12P3S2/c1-43-5-3-23-12-9-13(26-15(25-12)44-4-2-16(20,21)22)27(7-24-9)14-11(29)10(28)8(38-14)6-37-42(35,36)39-41(33,34)17(18,19)40(30,31)32/h7-8,10-11,14,28-29H,2-6H2,1H3,(H,33,34)(H,35,36)(H,23,25,26)(H2,30,31,32)/t8-,10-,11-,14-/m1/s1
IUPAC Name
[dichloro({[({[(2R,3S,4R,5R)-3,4-dihydroxy-5-(6-{[2-(methylsulfanyl)ethyl]amino}-2-[(3,3,3-trifluoropropyl)sulfanyl]-9H-purin-9-yl)oxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl})methyl]phosphonic acid
SMILES
CSCCNC1=C2N=CN([C@@H]3O[C@H](COP(O)(=O)OP(O)(=O)C(Cl)(Cl)P(O)(O)=O)[C@@H](O)[C@H]3O)C2=NC(SCCC(F)(F)F)=N1

Pharmacology

Indication

For use as an adjunct to percutaneous coronary intervention (PCI) for reducing the risk of periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis (ST) in patients in who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Cangrelor is a selective, reversible, P2Y12 platelet receptor antagonist which inhibits ADP platelet aggregation. ADP is typically released by damaged blood vessels, red blood cells, and/or platelets due to agonists stimulating platelet activity. ADP binds to P2Y12 to stimulate and complete platelet aggregation by inhibiting adenylyl cyclase by a Gi protein, thus potentiating dense granule secretion and increasing coagulation activity. Cangrelor acts on the same target as oral irreversible inhibitors clopidogrel and ticlopidine and has a similar mechanism of action, but is reversible and provides a fast onset and offset of action.

TargetActionsOrganism
AP2Y purinoceptor 12
inhibitor
Human
Absorption
Not Available
Volume of distribution

In a study in healthy volunteers administration at a dose of 30 mcg/kg bolus plus 4 mcg/kg/min showed a volume of distribution of 3.9 L.

Protein binding

about 97-98%.

Metabolism

Cangrelor is deactivated rapidly in the circulation by dephosphorylation to its primary metabolite, a nucleoside, which has negligible anti-platelet activity. Cangrelor's metabolism is independent of hepatic function and it does not interfere with other drugs metabolized by hepatic enzymes.

Route of elimination

Following IV administration of [3H] cangrelor, 58% of radioactivity was recovered in urine. The remaining 35% of radioactivity was in feces, presumably following biliary excretion.

Half life

The average elimination half-life of cangrelor is about 3-6 minutes.

Clearance

The mean clearance is about 43.2 L/h.

Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Cangrelor.
AcenocoumarolAcenocoumarol may increase the anticoagulant activities of Cangrelor.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Cangrelor.
AloxiprinThe risk or severity of adverse effects can be increased when Cangrelor is combined with Aloxiprin.
AlteplaseThe risk or severity of bleeding can be increased when Alteplase is combined with Cangrelor.
Aminosalicylic AcidThe risk or severity of bleeding can be increased when Aminosalicylic Acid is combined with Cangrelor.
AnagrelideThe risk or severity of bleeding can be increased when Anagrelide is combined with Cangrelor.
AncrodCangrelor may increase the anticoagulant activities of Ancrod.
AndrographolideAndrographolide may increase the anticoagulant activities of Cangrelor.
AnistreplaseCangrelor may increase the anticoagulant activities of Anistreplase.
Food Interactions
Not Available

References

General References
  1. Keating GM: Cangrelor: A Review in Percutaneous Coronary Intervention. Drugs. 2015 Aug;75(12):1425-34. doi: 10.1007/s40265-015-0445-3. [PubMed:26201463]
  2. Fugate SE, Cudd LA: Cangrelor for treatment of coronary thrombosis. Ann Pharmacother. 2006 May;40(5):925-30. Epub 2006 Apr 4. [PubMed:16595568]
External Links
KEGG Drug
D03359
PubChem Compound
9854012
PubChem Substance
310264872
ChemSpider
8029718
BindingDB
50118225
ChEBI
90841
ChEMBL
CHEMBL334966
PharmGKB
PA165945763
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cangrelor
ATC Codes
B01AC25 — Cangrelor
FDA label
Download (520 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
1CompletedTreatmentHealthy Volunteers1
1RecruitingPreventionComplete Obstruction of Systemic to Pulmonary Artery Shunt / Partial Obstruction of Systemic to Pulmonary Artery Shunt1
2CompletedNot AvailableCoronary Artery Disease2
2CompletedBasic ScienceCoronary Artery Disease1
2CompletedTreatmentAcute Coronary Syndromes (ACS)1
2CompletedTreatmentStable Angina (SA)1
3TerminatedTreatmentAcute Coronary Syndromes (ACS) / Atherosclerosis1
3TerminatedTreatmentAcute Coronary Syndromes (ACS) / Myocardial Infarction1
4Not Yet RecruitingTreatmentAcute Coronary Syndromes (ACS) / Myocardial Infarction / ST Elevation Myocardial Infarction (STEMI)1
4Not Yet RecruitingTreatmentCoronary Artery Disease / ST Elevation Myocardial Infarction (STEMI)1
4RecruitingTreatmentACS - Acute Coronary Syndrome / Cardiopulmonary Arrest With Successful Resuscitation / Hypothermia, Induced1
4RecruitingTreatmentAcute Coronary Syndromes (ACS) / High On-treatment Platelet Reactivity (HTPR) / Microvascular Obstruction (MVO) / ST Segment Elevation Myocardial Infarction (STEMI) / Thrombolysis in Myocardial Infarction (TIMI) / Unstable Angina (UA)1
4RecruitingTreatmentAcute Myocardial Infarction (AMI) / Shock, Cardiogenic1
4RecruitingTreatmentPercutaneous Coronary Intervention / ST Segment Elevation Myocardial Infarction (STEMI)1
Not AvailableRecruitingNot AvailableNon-ST Elevation Myocardial Infarction (NSTEMI)1
Not AvailableRecruitingTreatmentST Elevation Myocardial Infarction (STEMI)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous50 mg/1
Injection, powder, for solutionIntravenous50 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6130208No1998-06-292018-06-29Us
US6114313No1997-12-112017-12-11Us
US8680052No2013-03-092033-03-09Us
US8759316No2009-05-132029-05-13Us
US9295687No2015-07-102035-07-10Us
US9439921No2015-07-102035-07-10Us
US9427448No2010-11-102030-11-10Us
US9700575No2015-07-102035-07-10Us
US9925265No2009-05-132029-05-13Us
US10039780No2015-07-102035-07-10Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility4.33 mg/mLALOGPS
logP1.21ALOGPS
logP-0.12ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)0.8ChemAxon
pKa (Strongest Basic)2.61ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area255.91 Å2ChemAxon
Rotatable Bond Count16ChemAxon
Refractivity153.78 m3·mol-1ChemAxon
Polarizability63.92 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as purine ribonucleoside monophosphates. These are nucleotides consisting of a purine base linked to a ribose to which one monophosphate group is attached.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Purine nucleotides
Sub Class
Purine ribonucleotides
Direct Parent
Purine ribonucleoside monophosphates
Alternative Parents
Pentose phosphates / 6-alkylaminopurines / Glycosylamines / Monosaccharide phosphates / Bisphosphonates / Alkylarylthioethers / Aminopyrimidines and derivatives / Secondary alkylarylamines / Monoalkyl phosphates / N-substituted imidazoles
show 18 more
Substituents
Purine ribonucleoside monophosphate / Pentose phosphate / Pentose-5-phosphate / Glycosyl compound / N-glycosyl compound / 6-alkylaminopurine / 6-aminopurine / Monosaccharide phosphate / Bisphosphonate / Imidazopyrimidine
show 46 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Guanyl-nucleotide exchange factor activity
Specific Function
Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation.
Gene Name
P2RY12
Uniprot ID
Q9H244
Uniprot Name
P2Y purinoceptor 12
Molecular Weight
39438.355 Da
References
  1. Gan XD, Wei BZ, Fang D, Fang Q, Li KY, Ding SL, Peng S, Wan J: Efficacy and safety analysis of new P2Y12 inhibitors versus clopidogrel in patients with percutaneous coronary intervention: a meta-analysis. Curr Med Res Opin. 2015 Dec;31(12):2313-23. doi: 10.1185/03007995.2015.1098600. Epub 2015 Nov 4. [PubMed:26402735]

Drug created on March 19, 2008 10:33 / Updated on October 01, 2018 16:36