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
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
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/18796456 |
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18796456 |
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: Q9H244 Gene ID: 64805.0 Gene Symbol: P2RY12 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26402735 |
0.4 nM [IC50] | ||
Target ID: Q09QM4 Gene ID: 767613.0 Gene Symbol: Gpr17 Target Organism: Rattus norvegicus (Rat) Sources: https://www.ncbi.nlm.nih.gov/pubmed/27544384 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Preventing | KENGREAL Approved UseKENGREAL 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 Date2015 |
|||
Preventing | KENGREAL Approved UseKENGREAL 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 Date2015 |
|||
Primary | KENGREAL Approved UseKENGREAL 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 Date2015 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
299 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19779037 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19779037 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
249 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19779037 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19779037 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.61 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19779037 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19779037 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2% |
unknown, intravenous |
CANGRELOR plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
300 ug/kg single, intravenous Overdose Dose: 300 ug/kg Route: intravenous Route: single Dose: 300 ug/kg Sources: |
unhealthy n = 3 |
|
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 |
|
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%) Sources: Coronary artery dissection (0.6%) Coronary artery perforation (0.6%) Dyspnea (0.6%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/204958Orig1s000ClinPharmR.pdf#page=48 Page: 48.0 |
yes | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/204958Orig1s000ClinPharmR.pdf#page=48 Page: 48.0 |
yes |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
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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 |
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The effects of GPIIb-IIIa antagonists and a combination of three other antiplatelet agents on platelet-leukocyte interactions. | 2003 |
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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 |
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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 |
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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 |
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Influence of preparative procedures on assay of platelet function and apparent effects of antiplatelet agents. | 2007 Aug 15 |
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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 |
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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 |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27544384
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.
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C1327
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B01AC25
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CANGRELOR
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CHEMBL334966
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
SALT/SOLVATE (PARENT)