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

Molecular Formula Na
Molecular Weight 22.9898
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C17H21Cl2F3N5O12P3S2
Molecular Weight 772.327
Charge -4
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

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
Cangrelor AstraZeneca.
2001 Feb
ADP receptor antagonists inhibit platelet aggregation induced by the chemokines SDF-1, MDC and TARC.
2001 Feb 9
Activation of Gi-coupled receptors releases a tonic state of inhibited platelet aggregation.
2001 Mar
Effects of combining three different antiplatelet agents on platelets and leukocytes in whole blood in vitro.
2001 Sep
Role of the PAR4 thrombin receptor in stabilizing platelet-platelet aggregates as revealed by a patient with Hermansky-Pudlak syndrome.
2002 Apr
Role of ADP receptor P2Y(12) in platelet adhesion and thrombus formation in flowing blood.
2002 Apr 1
Safety profile and tolerability of intravenous AR-C69931MX, a new antiplatelet drug, in unstable angina pectoris and non-Q-wave myocardial infarction.
2002 May
Comparison of the pharmacodynamic effects of the platelet ADP receptor antagonists clopidogrel and AR-C69931MX in patients with ischaemic heart disease.
2002 Nov
Inhibition of ADP-induced P-selectin expression and platelet-leukocyte conjugate formation by clopidogrel and the P2Y12 receptor antagonist AR-C69931MX but not aspirin.
2002 Sep
Effects of the NHE-1 inhibitor cariporide alone or together with the P2Y12 antagonist AR-C 69331 MX on CD62p expression and formation of platelet-leukocyte aggregates.
2003
The effects of GPIIb-IIIa antagonists and a combination of three other antiplatelet agents on platelet-leukocyte interactions.
2003
Blockade of the platelet P2Y12 receptor by AR-C69931MX sustains coronary artery recanalization and improves the myocardial tissue perfusion in a canine thrombosis model.
2003 Feb 1
Agonist concentration-dependent differential responsivity of a human platelet purinergic receptor: pharmacological and kinetic studies of aggregation, deaggregation and shape change responses mediated by the purinergic P2Y1 receptor in vitro.
2003 Nov-Dec
P2Y12 receptor stimulation inhibits beta-adrenergic receptor-induced differentiation by reversing the cyclic AMP-dependent inhibition of protein kinase B.
2004 Apr
Autoinhibition of transmitter release from PC12 cells and sympathetic neurons through a P2Y receptor-mediated inhibition of voltage-gated Ca2+ channels.
2004 Dec
Inhibition of ADP-induced intracellular Ca2+ responses and platelet aggregation by the P2Y12 receptor antagonists AR-C69931MX and clopidogrel is enhanced by prostaglandin E1.
2004 Jan
Costimulation of the Gi-coupled ADP receptor and the Gq-coupled TXA2 receptor is required for ERK2 activation in collagen-induced platelet aggregation.
2004 Jan 2
Potentiation of platelet aggregation by heparin in human whole blood is attenuated by P2Y12 and P2Y1 antagonists but not aspirin.
2005
Preclinical and clinical studies with selective reversible direct P2Y12 antagonists.
2005 Apr
P2Y12 receptors play a significant role in the development of platelet microaggregation in patients with diabetes.
2005 Feb
Regulation of tissue factor-induced coagulation and platelet aggregation in flowing whole blood.
2005 Jan
Inhibitory effects of P2Y12 receptor antagonists on TRAP-induced platelet aggregation, procoagulant activity, microparticle formation and intracellular calcium responses in patients with acute coronary syndromes.
2005 Mar
P2Y receptor antagonists in thrombosis.
2005 Mar
Evidence that the purinergic receptor P2Y12 potentiates platelet shape change by a Rho kinase-dependent mechanism.
2005 Nov
The nucleotide receptor P2Y13 is a key regulator of hepatic high-density lipoprotein (HDL) endocytosis.
2005 Nov
Metabotropic P2Y1 receptors inhibit P2X3 receptor-channels in rat dorsal root ganglion neurons.
2005 Oct 3
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
Evaluation of platelet function, a method comparison.
2006 Feb
Can the PFA-100 be modified to detect P2Y12 inhibition?
2006 Jun
Cangrelor for treatment of coronary thrombosis.
2006 May
ADP receptors: inhibitory strategies for antiplatelet therapy.
2006 Sep 1
Optimal management of platelet function after coronary stenting.
2007 Feb
Platelet P2 receptors: old and new targets for antithrombotic drugs.
2007 Jan
Glycoprotein Ibalpha inhibition and ADP receptor antagonists, but not aspirin, reduce platelet thrombus formation in flowing blood exposed to atherosclerotic plaques.
2007 Mar
Primary and secondary agonists can use P2X(1) receptors as a major pathway to increase intracellular Ca(2+) in the human platelet.
2007 May
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
Pharmacology of emerging novel platelet inhibitors.
2008 Aug
Peripheral tachykinins and the neurokinin receptor NK1 are required for platelet thrombus formation.
2008 Jan 15
New antiplatelet therapies in development.
2008 Jul 1
Multiple electrode aggregometry and P2Y(12) antagonists.
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
Coronary atherothrombotic disease: progress in antiplatelet therapy.
2008 May
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.
Substance Class Chemical
Created
by admin
on Wed Jul 05 23:17:11 UTC 2023
Edited
by admin
on Wed Jul 05 23:17:11 UTC 2023
Record UNII
2144G00Y7W
Record Status Validated (UNII)
Record Version
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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 Wed Jul 05 23:17:11 UTC 2023 , Edited by admin on Wed Jul 05 23:17:11 UTC 2023
EMA ASSESSMENT REPORTS KENGREXAL (AUTHORIZED: VASCULAR SURGICAR PROCEDURES
Created by admin on Wed Jul 05 23:17:11 UTC 2023 , Edited by admin on Wed Jul 05 23:17:11 UTC 2023
EMA ASSESSMENT REPORTS KENGREXAL (AUTHORIZED: ACUTE CORONARY SYNDROME)
Created by admin on Wed Jul 05 23:17:11 UTC 2023 , Edited by admin on Wed Jul 05 23:17:11 UTC 2023
Code System Code Type Description
SMS_ID
100000168765
Created by admin on Wed Jul 05 23:17:11 UTC 2023 , Edited by admin on Wed Jul 05 23:17:11 UTC 2023
PRIMARY
DRUG BANK
DBSALT001292
Created by admin on Wed Jul 05 23:17:11 UTC 2023 , Edited by admin on Wed Jul 05 23:17:11 UTC 2023
PRIMARY
RXCUI
1656051
Created by admin on Wed Jul 05 23:17:11 UTC 2023 , Edited by admin on Wed Jul 05 23:17:11 UTC 2023
PRIMARY RxNorm
PUBCHEM
10260031
Created by admin on Wed Jul 05 23:17:11 UTC 2023 , Edited by admin on Wed Jul 05 23:17:11 UTC 2023
PRIMARY
CAS
163706-36-3
Created by admin on Wed Jul 05 23:17:11 UTC 2023 , Edited by admin on Wed Jul 05 23:17:11 UTC 2023
PRIMARY
USAN
RR-129
Created by admin on Wed Jul 05 23:17:11 UTC 2023 , Edited by admin on Wed Jul 05 23:17:11 UTC 2023
PRIMARY
FDA UNII
2144G00Y7W
Created by admin on Wed Jul 05 23:17:11 UTC 2023 , Edited by admin on Wed Jul 05 23:17:11 UTC 2023
PRIMARY
NCI_THESAURUS
C76396
Created by admin on Wed Jul 05 23:17:11 UTC 2023 , Edited by admin on Wed Jul 05 23:17:11 UTC 2023
PRIMARY
ChEMBL
CHEMBL334966
Created by admin on Wed Jul 05 23:17:11 UTC 2023 , Edited by admin on Wed Jul 05 23:17:11 UTC 2023
PRIMARY
MERCK INDEX
M3019
Created by admin on Wed Jul 05 23:17:11 UTC 2023 , Edited by admin on Wed Jul 05 23:17:11 UTC 2023
PRIMARY Merck Index
EPA CompTox
DTXSID50167652
Created by admin on Wed Jul 05 23:17:11 UTC 2023 , Edited by admin on Wed Jul 05 23:17:11 UTC 2023
PRIMARY
EVMPD
SUB182388
Created by admin on Wed Jul 05 23:17:11 UTC 2023 , Edited by admin on Wed Jul 05 23:17:11 UTC 2023
PRIMARY
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PARENT -> SALT/SOLVATE
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ACTIVE MOIETY