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

Details

Stereochemistry ABSOLUTE
Molecular Formula C17H25Cl2F3N5O12P3S2
Molecular Weight 776.3619
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CANGRELOR

SMILES

CSCCNc1c2c(nc(n1)SCCC(F)(F)F)n(cn2)[C@@]3([H])[C@@]([H])([C@@]([H])([C@@]([H])(COP(=O)(O)OP(=O)(C(Cl)(Cl)P(=O)(O)O)O)O3)O)O

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

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
ADP receptor antagonists inhibit platelet aggregation induced by the chemokines SDF-1, MDC and TARC.
2001 Feb 9
Comparison of the pharmacodynamic effects of the platelet ADP receptor antagonists clopidogrel and AR-C69931MX in patients with ischaemic heart disease.
2002 Nov
The effects of GPIIb-IIIa antagonists and a combination of three other antiplatelet agents on platelet-leukocyte interactions.
2003
In vivo blockade of platelet ADP receptor P2Y12 reduces embolus and thrombus formation but not thrombus stability.
2003 Mar 1
Preclinical and clinical studies with selective reversible direct P2Y12 antagonists.
2005 Apr
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
P2Y12 ADP receptor-dependent tyrosine phosphorylation of proteins of 27 and 31 kDa in thrombin-stimulated human platelets.
2005 May
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
Cangrelor for treatment of coronary thrombosis.
2006 May
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
Inhibition of the platelet P2Y12 receptor for adenosine diphosphate potentiates the antiplatelet effect of prostacyclin.
2007 Mar
Involvement of P2X and P2Y receptors in microglial activation in vivo.
2007 Sep
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
Antiplatelet therapy in acute coronary syndromes.
2008 Jul
The ATP-gated P2X1 receptor plays a pivotal role in activation of aspirin-treated platelets by thrombin and epinephrine.
2008 Jul 4
Changing trends in anti-coagulant therapies. Are heparins and oral anti-coagulants challenged?
2008 Jun
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
Coronary atherothrombotic disease: progress in antiplatelet therapy.
2008 May
Antiplatelet therapy for secondary prevention of noncardioembolic ischemic stroke: a critical review.
2008 May
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 [WHO-DD]
Common Name English
CANGRELOR [USAN]
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 Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
NCI_THESAURUS C1327
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
WHO-ATC B01AC25
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
Code System Code Type Description
MERCK INDEX
M3019
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
PRIMARY Merck Index
PUBCHEM
9854012
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
PRIMARY
EVMPD
SUB26448
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
PRIMARY
INN
7883
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
PRIMARY
DRUG CENTRAL
5006
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
PRIMARY
NCI_THESAURUS
C76395
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
PRIMARY
MESH
C117446
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
PRIMARY
IUPHAR
1776
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
PRIMARY
RXCUI
1656052
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
PRIMARY RxNorm
FDA UNII
6AQ1Y404U7
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
PRIMARY
NDF-RT
N0000182143
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
PRIMARY P2Y12 Receptor Antagonists [MoA]
EPA CompTox
163706-06-7
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
PRIMARY
DRUG BANK
DB06441
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
PRIMARY
WIKIPEDIA
CANGRELOR
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
PRIMARY
CAS
163706-06-7
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
PRIMARY
ChEMBL
CHEMBL334966
Created by admin on Sat Jun 26 06:09:08 UTC 2021 , Edited by admin on Sat Jun 26 06:09:08 UTC 2021
PRIMARY