U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C17H21Cl2F3N5O12P3S2.4Na
Molecular Weight 864.287
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CANGRELOR TETRASODIUM

SMILES

[Na+].[Na+].[Na+].[Na+].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

InChI

InChIKey=COWWROCHWNGJHQ-OPKBHZIBSA-J
InChI=1S/C17H25Cl2F3N5O12P3S2.4Na/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);;;;/q;4*+1/p-4/t8-,10-,11-,14-;;;;/m1..../s1

HIDE SMILES / InChI
Cangrelor is a P2Y12 inhibitor that has been approved as an antiplatelet drug. It is marketed in the US under the brand name Kengreal and in Europe as Kengrexal. Cangrelor is an intravenous, direct-acting reversible P2Y12 inhibitor for patients undergoing percutaneous coronary intervention.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Q9H244
Gene ID: 64805.0
Gene Symbol: P2RY12
Target Organism: Homo sapiens (Human)
0.4 nM [IC50]
Target ID: Q09QM4
Gene ID: 767613.0
Gene Symbol: Gpr17
Target Organism: Rattus norvegicus (Rat)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
KENGREAL

Approved Use

KENGREAL is indicated as an adjunct to percutaneous coronary intervention (PCI) to reduce the risk of periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis (ST) in patients who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor [see Clinical Studies ( 14.1 )

Launch Date

1.43493117E12
Preventing
KENGREAL

Approved Use

KENGREAL is indicated as an adjunct to percutaneous coronary intervention (PCI) to reduce the risk of periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis (ST) in patients who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor [see Clinical Studies ( 14.1 )

Launch Date

1.43493117E12
Primary
KENGREAL

Approved Use

KENGREAL is indicated as an adjunct to percutaneous coronary intervention (PCI) to reduce the risk of periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis (ST) in patients who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor [see Clinical Studies ( 14.1 )

Launch Date

1.43493117E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
299 ng/mL
135 μg/kg other, intravenous
dose: 135 μg/kg
route of administration: Intravenous
experiment type: OTHER
co-administered:
CANGRELOR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
635 ng/mL
270 μg/kg other, intravenous
dose: 270 μg/kg
route of administration: Intravenous
experiment type: OTHER
co-administered:
CANGRELOR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
249 ng × h/mL
135 μg/kg other, intravenous
dose: 135 μg/kg
route of administration: Intravenous
experiment type: OTHER
co-administered:
CANGRELOR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
478 ng × h/mL
270 μg/kg other, intravenous
dose: 270 μg/kg
route of administration: Intravenous
experiment type: OTHER
co-administered:
CANGRELOR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.61 min
135 μg/kg other, intravenous
dose: 135 μg/kg
route of administration: Intravenous
experiment type: OTHER
co-administered:
CANGRELOR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3.71 min
270 μg/kg other, intravenous
dose: 270 μg/kg
route of administration: Intravenous
experiment type: OTHER
co-administered:
CANGRELOR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
unknown, intravenous
CANGRELOR plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
300 ug/kg single, intravenous
Overdose
Dose: 300 ug/kg
Route: intravenous
Route: single
Dose: 300 ug/kg
Sources:
unhealthy
n = 3
Health Status: unhealthy
Population Size: 3
Sources:
12 ug/kg/min single, intravenous
Overdose
Dose: 12 ug/kg/min
Route: intravenous
Route: single
Dose: 12 ug/kg/min
Sources:
unhealthy
n = 1
Health Status: unhealthy
Population Size: 1
Sources:
30 ug/kg single, intravenous
Recommended
Dose: 30 ug/kg
Route: intravenous
Route: single
Dose: 30 ug/kg
Sources:
unhealthy
n = 5529
Health Status: unhealthy
Sex: M+F
Population Size: 5529
Sources:
Disc. AE: Bleeding, Coronary artery dissection...
AEs leading to
discontinuation/dose reduction:
Bleeding (0.3%)
Coronary artery dissection (0.6%)
Coronary artery perforation (0.6%)
Dyspnea (0.6%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Bleeding 0.3%
Disc. AE
30 ug/kg single, intravenous
Recommended
Dose: 30 ug/kg
Route: intravenous
Route: single
Dose: 30 ug/kg
Sources:
unhealthy
n = 5529
Health Status: unhealthy
Sex: M+F
Population Size: 5529
Sources:
Coronary artery dissection 0.6%
Disc. AE
30 ug/kg single, intravenous
Recommended
Dose: 30 ug/kg
Route: intravenous
Route: single
Dose: 30 ug/kg
Sources:
unhealthy
n = 5529
Health Status: unhealthy
Sex: M+F
Population Size: 5529
Sources:
Coronary artery perforation 0.6%
Disc. AE
30 ug/kg single, intravenous
Recommended
Dose: 30 ug/kg
Route: intravenous
Route: single
Dose: 30 ug/kg
Sources:
unhealthy
n = 5529
Health Status: unhealthy
Sex: M+F
Population Size: 5529
Sources:
Dyspnea 0.6%
Disc. AE
30 ug/kg single, intravenous
Recommended
Dose: 30 ug/kg
Route: intravenous
Route: single
Dose: 30 ug/kg
Sources:
unhealthy
n = 5529
Health Status: unhealthy
Sex: M+F
Population Size: 5529
Sources:
Overview

OverviewOther

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 58 uM]
no [IC50 58 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no
no
weak
weak
yes
yes
Drug as victim
PubMed

PubMed

TitleDatePubMed
Effects on blood compatibility in vitro by combining a direct P2Y12 receptor inhibitor and heparin coating of stents.
2006 Aug
Brief review: coronary drug-eluting stents and anesthesia.
2006 Dec
Comparison of VASP-phosphorylation assay to light-transmission aggregometry in assessing inhibition of the platelet ADP P2Y12 receptor.
2006 Dec
Therapeutic goals for effective platelet inhibition: a consensus document.
2006 Fall
ADP receptors: inhibitory strategies for antiplatelet therapy.
2006 Jun
Can the PFA-100 be modified to detect P2Y12 inhibition?
2006 Jun
Critical role of ADP interaction with P2Y12 receptor in the maintenance of alpha(IIb)beta3 activation: association with Rap1B activation.
2006 Jun
Cangrelor for treatment of coronary thrombosis.
2006 May
Aspirin and clopidogrel resistance: consideration and management.
2006 Oct
ADP receptors: inhibitory strategies for antiplatelet therapy.
2006 Sep 1
ADP receptor antagonism: what's in the pipeline?
2007
Influence of preparative procedures on assay of platelet function and apparent effects of antiplatelet agents.
2007 Aug 15
Enhanced platelet aggregation and activation under conditions of hypothermia.
2007 Dec
Optimal management of platelet function after coronary stenting.
2007 Feb
Platelet P2 receptors: old and new targets for antithrombotic drugs.
2007 Jan
New antiplatelet therapies for acute coronary syndromes.
2007 Jul
Residual platelet ADP reactivity after clopidogrel treatment is dependent on activation of both the unblocked P2Y(1) and the P2Y (12) receptor and is correlated with protein expression of P2Y (12).
2007 Jun
Glycoprotein Ibalpha inhibition and ADP receptor antagonists, but not aspirin, reduce platelet thrombus formation in flowing blood exposed to atherosclerotic plaques.
2007 Mar
Dyspnoea after antiplatelet agents: the AZD6140 controversy.
2007 Mar
Inhibition of the platelet P2Y12 receptor for adenosine diphosphate potentiates the antiplatelet effect of prostacyclin.
2007 Mar
Seven Golden Rules for heuristic filtering of molecular formulas obtained by accurate mass spectrometry.
2007 Mar 27
Primary and secondary agonists can use P2X(1) receptors as a major pathway to increase intracellular Ca(2+) in the human platelet.
2007 May
Antithrombotic therapy and the transition to the catheterization laboratory in UA/NSTEMI.
2007 Oct
Preliminary experience with intravenous P2Y12 platelet receptor inhibition as an adjunct to reduced-dose alteplase during acute myocardial infarction: results of the Safety, Tolerability and Effect on Patency in Acute Myocardial Infarction (STEP-AMI) angiographic trial.
2007 Oct
Involvement of P2X and P2Y receptors in microglial activation in vivo.
2007 Sep
Optimizing platelet P2Y12 inhibition for patients undergoing PCI.
2007 Summer
Transitioning patients from cangrelor to clopidogrel: pharmacodynamic evidence of a competitive effect.
2008
Detection of P2Y(14) protein in platelets and investigation of the role of P2Y(14) in platelet function in comparison with the EP(3) receptor.
2008 Aug
Clinical overview of promising nonthienopyridine antiplatelet agents.
2008 Aug
Pharmacology of emerging novel platelet inhibitors.
2008 Aug
Survival of heparins, oral anticoagulants, and aspirin after the year 2010.
2008 Feb
Modulation of platelet and leucocyte function by a Chinese herbal formulation as compared with conventional antiplatelet agents.
2008 Feb
Peripheral tachykinins and the neurokinin receptor NK1 are required for platelet thrombus formation.
2008 Jan 15
Antiplatelet therapy in acute coronary syndromes.
2008 Jul
The reversible P2Y antagonist cangrelor influences the ability of the active metabolites of clopidogrel and prasugrel to produce irreversible inhibition of platelet function.
2008 Jul
New antiplatelet therapies in development.
2008 Jul 1
The ATP-gated P2X1 receptor plays a pivotal role in activation of aspirin-treated platelets by thrombin and epinephrine.
2008 Jul 4
Multiple electrode aggregometry and P2Y(12) antagonists.
2008 Jun
Changing trends in anti-coagulant therapies. Are heparins and oral anti-coagulants challenged?
2008 Jun
GPR17: molecular modeling and dynamics studies of the 3-D structure and purinergic ligand binding features in comparison with P2Y receptors.
2008 Jun 4
UCB Pharma research day-25 October 2007 'Glia-neuron interactions and purinergic receptors in neurological disorders'.
2008 Mar
P2 receptors, platelet function and pharmacological implications.
2008 Mar
Acyl derivatives of coenzyme A inhibit platelet function via antagonism at P2Y1 and P2Y12 receptors: a new finding that may influence the design of anti-thrombotic agents.
2008 Mar
The active metabolite of prasugrel effectively blocks the platelet P2Y12 receptor and inhibits procoagulant and pro-inflammatory platelet responses.
2008 Mar
P2Y12 antagonism: promises and challenges.
2008 Mar
Coronary atherothrombotic disease: progress in antiplatelet therapy.
2008 May
Antiplatelet therapy for secondary prevention of noncardioembolic ischemic stroke: a critical review.
2008 May
Akt activation is involved in P2Y12 receptor-mediated chemotaxis of microglia.
2008 May 15
P2Y12 receptors in spinal microglia are required for neuropathic pain after peripheral nerve injury.
2008 May 7
Development of selective agonists and antagonists of P2Y receptors.
2009 Mar
Patents

Sample Use Guides

Cangrelor is the active ingredient in KENGREAL which is administered at 30 micro-g/kg as an intravenous bolus prior to PCI and followed immediately by a 4 micro-g/kg/min IV infusion for at least 2 hours or duration of the procedure, whichever is longer.
Route of Administration: Intravenous
In Vitro Use Guide
Curator's Comment: referenced study was conducted on rat
Primary OPCs were isolated from mixed glial cultures from postnatal day 2 Sprague-Dawley rat cortex. Cells were suspended in NM15 Medium containing MEM, 15% heat-inactivated fetal bovine serum, 6 mg/mL glucose, 100 U/mL penicillin, 100 micro-g/mL streptomycin, 5 micro-g/mL insulin, and incubated at room Temperature in a RAN2-Ab-precoated plate. After 20 min, floating cells were transferred to a second RAN2-Ab-precoated plate and incubated for additional 20 min at RT. To verify whether OPCs can generate neurons under a standard protocol of oligodendrocyte differentiation, cells were plated in Neurobasal medium with 2 % B27 Supplement, 2 mM L-glutamine, 10 ng/ml human platelet-derived growth factor-BB, and 10 ng/ml human basic fibroblast growth factor to promote proliferation. After 2 days, OPCs were shifted to differentiating medium, and either grown under control conditions or exposed to the anticonvulsant agent valproic acid (VPA, 500 micro-M) for 24–72 h, fixed, and immunostained for GPR17 and the neuronal marker βIII-tubulin. The GPR17 antagonist Cangrelor (10 micro-M) was used in parallel to VPS (500 micro-M). The percentage of GPR17/βIII-tub double-positive cells over the total cell population increased in cultures treated with either Cangrelor or VPA. It was also observed that in Cangralor treated cells the percentage of NG2/GPR17 double-positive cells calculated on the total number of cells decreased, indicating that a subset of OPCs is shifting its fate from oligodendrocytes to neurons.
Name Type Language
CANGRELOR TETRASODIUM
MART.   USAN   WHO-DD  
USAN  
Official Name English
CANGRELOR TETRASODIUM [MART.]
Common Name English
CANGRELOR TETRASODIUM SALT [MI]
Common Name English
Cangrelor tetrasodium [WHO-DD]
Common Name English
AR-C69931MX
Code English
CANGRELOR TETRASODIUM SALT
MI  
Common Name English
CANGRELOR TETRASODIUM [USAN]
Common Name English
KENGREXAL
Brand Name English
Classification Tree Code System Code
NCI_THESAURUS C1327
Created by admin on Fri Dec 15 15:48:45 UTC 2023 , Edited by admin on Fri Dec 15 15:48:45 UTC 2023
EMA ASSESSMENT REPORTS KENGREXAL (AUTHORIZED: VASCULAR SURGICAR PROCEDURES
Created by admin on Fri Dec 15 15:48:45 UTC 2023 , Edited by admin on Fri Dec 15 15:48:45 UTC 2023
EMA ASSESSMENT REPORTS KENGREXAL (AUTHORIZED: ACUTE CORONARY SYNDROME)
Created by admin on Fri Dec 15 15:48:45 UTC 2023 , Edited by admin on Fri Dec 15 15:48:45 UTC 2023
Code System Code Type Description
SMS_ID
100000168765
Created by admin on Fri Dec 15 15:48:45 UTC 2023 , Edited by admin on Fri Dec 15 15:48:45 UTC 2023
PRIMARY
DRUG BANK
DBSALT001292
Created by admin on Fri Dec 15 15:48:45 UTC 2023 , Edited by admin on Fri Dec 15 15:48:45 UTC 2023
PRIMARY
RXCUI
1656051
Created by admin on Fri Dec 15 15:48:45 UTC 2023 , Edited by admin on Fri Dec 15 15:48:45 UTC 2023
PRIMARY RxNorm
PUBCHEM
10260031
Created by admin on Fri Dec 15 15:48:45 UTC 2023 , Edited by admin on Fri Dec 15 15:48:45 UTC 2023
PRIMARY
CAS
163706-36-3
Created by admin on Fri Dec 15 15:48:45 UTC 2023 , Edited by admin on Fri Dec 15 15:48:45 UTC 2023
PRIMARY
USAN
RR-129
Created by admin on Fri Dec 15 15:48:45 UTC 2023 , Edited by admin on Fri Dec 15 15:48:45 UTC 2023
PRIMARY
FDA UNII
2144G00Y7W
Created by admin on Fri Dec 15 15:48:45 UTC 2023 , Edited by admin on Fri Dec 15 15:48:45 UTC 2023
PRIMARY
NCI_THESAURUS
C76396
Created by admin on Fri Dec 15 15:48:45 UTC 2023 , Edited by admin on Fri Dec 15 15:48:45 UTC 2023
PRIMARY
ChEMBL
CHEMBL334966
Created by admin on Fri Dec 15 15:48:45 UTC 2023 , Edited by admin on Fri Dec 15 15:48:45 UTC 2023
PRIMARY
MERCK INDEX
m3019
Created by admin on Fri Dec 15 15:48:45 UTC 2023 , Edited by admin on Fri Dec 15 15:48:45 UTC 2023
PRIMARY Merck Index
EPA CompTox
DTXSID50167652
Created by admin on Fri Dec 15 15:48:45 UTC 2023 , Edited by admin on Fri Dec 15 15:48:45 UTC 2023
PRIMARY
EVMPD
SUB182388
Created by admin on Fri Dec 15 15:48:45 UTC 2023 , Edited by admin on Fri Dec 15 15:48:45 UTC 2023
PRIMARY