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

Molecular Formula C17H25Cl2F3N5O12P3S2
Molecular Weight 776.359
Charge 0
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

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
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
Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors.
2001 Mar 15
A Gi-dependent pathway is required for activation of the small GTPase Rap1B in human platelets.
2002 Apr 5
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
Glycoprotein IIb/IIIa and P2Y12 receptor antagonists yield additive inhibition of platelet aggregation, granule secretion, soluble CD40L release and procoagulant responses.
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
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
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
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
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
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
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
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
Multiple electrode aggregometry and P2Y(12) antagonists.
2008 Jun
Changing trends in anti-coagulant therapies. Are heparins and oral anti-coagulants challenged?
2008 Jun
P2 receptors, platelet function and pharmacological implications.
2008 Mar
P2Y12 antagonism: promises and challenges.
2008 Mar
Coronary atherothrombotic disease: progress in antiplatelet therapy.
2008 May
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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:10:10 GMT 2023
Edited
by admin
on Fri Dec 15 16:10:10 GMT 2023
Record UNII
6AQ1Y404U7
Record Status Validated (UNII)
Record Version
  • Download
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
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
NCI_THESAURUS
C76395
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
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
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
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
Related Record Type Details
TARGET -> INHIBITOR
EXCRETED UNCHANGED
The chromatographic method used did not differentiate between cangrelor (AR-69931) and one of its metabolite AR-C90439 in this study and so the presence or absence of cangrelor (AR-C69931) in urine or feces cannot be confirmed.
SALT/SOLVATE -> PARENT
BINDER->LIGAND
BINDING
Related Record Type Details
METABOLITE -> PARENT
MINOR
FECAL
METABOLITE -> PARENT
MINOR
FECAL
METABOLITE -> PARENT
MAJOR
PLASMA
METABOLITE -> PARENT
MAJOR
URINE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC INTRAVENOUS ADMINISTRATION

Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC