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

Details

Stereochemistry ABSOLUTE
Molecular Formula C17H25Cl2F3N5O12P3S2
Molecular Weight 776.359
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CANGRELOR

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

InChI

InChIKey=PAEBIVWUMLRPSK-IDTAVKCVSA-N
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

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

2015
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

2015
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

2015
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
The medicinal chemistry of the P2 receptor family.
2001
Blockade of adenosine diphosphate receptors P2Y(12) and P2Y(1) is required to inhibit platelet aggregation in whole blood under flow.
2001 Dec 1
Cangrelor AstraZeneca.
2001 Feb
ADP receptor antagonists inhibit platelet aggregation induced by the chemokines SDF-1, MDC and TARC.
2001 Feb 9
Role of the PAR4 thrombin receptor in stabilizing platelet-platelet aggregates as revealed by a patient with Hermansky-Pudlak syndrome.
2002 Apr
Safety profile and tolerability of intravenous AR-C69931MX, a new antiplatelet drug, in unstable angina pectoris and non-Q-wave myocardial infarction.
2002 May
Functional significance of adenosine 5'-diphosphate receptor (P2Y(12)) in platelet activation initiated by binding of von Willebrand factor to platelet GP Ibalpha induced by conditions of high shear rate.
2002 May 28
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
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
A selective role for phosphatidylinositol 3,4,5-trisphosphate in the Gi-dependent activation of platelet Rap1B.
2003 Jan 3
Pharmacological characterization of the human P2Y13 receptor.
2003 Jul
Pharmacodynamic profile of antiplatelet agents: marked differences between single versus costimulation with platelet activators.
2004
Autoinhibition of transmitter release from PC12 cells and sympathetic neurons through a P2Y receptor-mediated inhibition of voltage-gated Ca2+ channels.
2004 Dec
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
P2Y receptor antagonists in thrombosis.
2005 Mar
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
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
Evaluation of platelet function, a method comparison.
2006 Feb
ADP receptors: inhibitory strategies for antiplatelet therapy.
2006 Jun
Can the PFA-100 be modified to detect P2Y12 inhibition?
2006 Jun
Initial experience with an intravenous P2Y12 platelet receptor antagonist in patients undergoing percutaneous coronary intervention: results from a 2-part, phase II, multicenter, randomized, placebo- and active-controlled trial.
2006 Mar
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
Platelet P2 receptors: old and new targets for antithrombotic drugs.
2007 Jan
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
Antithrombotic therapy and the transition to the catheterization laboratory in UA/NSTEMI.
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
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
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
Akt activation is involved in P2Y12 receptor-mediated chemotaxis of microglia.
2008 May 15
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
DASH   INN   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
(DICHLOROMETHYLENE)DIPHOSPHONIC N-(2-(METHYLSULFANYL)ETHYL)-2-((3,3,3-TRIFLUOROPROPYL)SULFANYL-5'-ADENYLIC MONOANHYDRIDE
Common Name English
KENGREAL
Brand Name English
CANGRELOR [MI]
Common Name English
CANGRELOR [ORANGE BOOK]
Common Name English
cangrelor [INN]
Common Name English
CANGRELOR [USAN]
Common Name English
Cangrelor [WHO-DD]
Common Name English
5'-ADENYLICACID, N-(2-(METHYLTHIO)ETHYL)-2-((3,3,3-TRIFLUOROPROPYL)THIO)-, MONOANHYDRIDE WITH (DICHLOROMETHYLENE)BIS(PHOSPHONIC ACID)
Common Name English
AR-C69931XX
Code English
Classification Tree Code System Code
NDF-RT N0000182142
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
NCI_THESAURUS C1327
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
WHO-ATC B01AC25
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
Code System Code Type Description
MERCK INDEX
m3019
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY Merck Index
PUBCHEM
9854012
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
DAILYMED
6AQ1Y404U7
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
CHEBI
90841
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
EVMPD
SUB26448
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
INN
7883
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
DRUG CENTRAL
5006
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PRIMARY
NCI_THESAURUS
C76395
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PRIMARY
SMS_ID
100000092769
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
MESH
C117446
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
CHEBI
90836
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
IUPHAR
1776
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PRIMARY
RXCUI
1656052
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY RxNorm
FDA UNII
6AQ1Y404U7
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
NDF-RT
N0000182143
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY P2Y12 Receptor Antagonists [MoA]
USAN
RR-120
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
DRUG BANK
DB06441
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
WIKIPEDIA
CANGRELOR
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
CAS
163706-06-7
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
EPA CompTox
DTXSID90167651
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
ChEMBL
CHEMBL334966
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY