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
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
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 |
|
Activation of Gi-coupled receptors releases a tonic state of inhibited platelet aggregation. | 2001 Mar |
|
A Gi-dependent pathway is required for activation of the small GTPase Rap1B in human platelets. | 2002 Apr 5 |
|
Safety profile and tolerability of intravenous AR-C69931MX, a new antiplatelet drug, in unstable angina pectoris and non-Q-wave myocardial infarction. | 2002 May |
|
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 |
|
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 |
|
Advantages of fast-acting ADP receptor blockade in ischemic heart disease. | 2003 Feb 1 |
|
A selective role for phosphatidylinositol 3,4,5-trisphosphate in the Gi-dependent activation of platelet Rap1B. | 2003 Jan 3 |
|
Effects of inhibition of P2Y(1) and P2Y(12) on whole blood clotting, coagulum elasticity and fibrinolysis resistance studied with free oscillation rheometry. | 2003 Mar 15 |
|
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 |
|
Potential value of triple antiplatelet therapy for secondary stroke prevention. | 2003 Oct |
|
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 |
|
Evidence that the purinergic receptor P2Y12 potentiates platelet shape change by a Rho kinase-dependent mechanism. | 2005 Nov |
|
Therapeutic goals for effective platelet inhibition: a consensus document. | 2006 Fall |
|
ADP receptors: inhibitory strategies for antiplatelet therapy. | 2006 Jun |
|
Critical role of ADP interaction with P2Y12 receptor in the maintenance of alpha(IIb)beta3 activation: association with Rap1B activation. | 2006 Jun |
|
Seven Golden Rules for heuristic filtering of molecular formulas obtained by accurate mass spectrometry. | 2007 Mar 27 |
|
Clinical overview of promising nonthienopyridine antiplatelet agents. | 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 |
|
Changing trends in anti-coagulant therapies. Are heparins and oral anti-coagulants challenged? | 2008 Jun |
|
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 |
|
The active metabolite of prasugrel effectively blocks the platelet P2Y12 receptor and inhibits procoagulant and pro-inflammatory platelet responses. | 2008 Mar |
|
Antiplatelet therapy for secondary prevention of noncardioembolic ischemic stroke: a critical review. | 2008 May |
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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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C1327
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EMA ASSESSMENT REPORTS |
KENGREXAL (AUTHORIZED: VASCULAR SURGICAR PROCEDURES
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EMA ASSESSMENT REPORTS |
KENGREXAL (AUTHORIZED: ACUTE CORONARY SYNDROME)
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ACTIVE MOIETY
SUBSTANCE RECORD