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
Molecular Formula | C17H21Cl2F3N5O12P3S2 |
Molecular Weight | 772.327 |
Charge | -4 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 4 / 4 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
Molecular Formula | Na |
Molecular Weight | 22.9898 |
Charge | 1 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
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 |
---|---|---|
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 |
|
Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors. | 2001 Mar 15 |
|
Effects of combining three different antiplatelet agents on platelets and leukocytes in whole blood in vitro. | 2001 Sep |
|
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 |
|
Purine and pyrimidine (P2) receptors as drug targets. | 2002 Sep 12 |
|
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 |
|
Potential value of triple antiplatelet therapy for secondary stroke prevention. | 2003 Oct |
|
Investigation of the PADA as a method for monitoring GPIIb/IIIa inhibitors and other antiplatelet agents. | 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 |
|
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 |
|
P2Y receptor antagonists in thrombosis. | 2005 Mar |
|
P2Y12 ADP receptor-dependent tyrosine phosphorylation of proteins of 27 and 31 kDa in thrombin-stimulated human platelets. | 2005 May |
|
Evidence that the purinergic receptor P2Y12 potentiates platelet shape change by a Rho kinase-dependent mechanism. | 2005 Nov |
|
Metabotropic P2Y1 receptors inhibit P2X3 receptor-channels in rat dorsal root ganglion neurons. | 2005 Oct 3 |
|
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 |
|
Critical role of ADP interaction with P2Y12 receptor in the maintenance of alpha(IIb)beta3 activation: association with Rap1B activation. | 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 |
|
P2Y12 receptor-mediated potentiation of thrombin-induced thromboxane A2 generation in platelets occurs through regulation of Erk1/2 activation. | 2006 Mar |
|
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 |
|
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 |
|
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 |
|
Primary and secondary agonists can use P2X(1) receptors as a major pathway to increase intracellular Ca(2+) in the human platelet. | 2007 May |
|
Antithrombotic therapy and the transition to the catheterization laboratory in UA/NSTEMI. | 2007 Oct |
|
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 |
|
Optimizing platelet P2Y12 inhibition for patients undergoing PCI. | 2007 Summer |
|
Clinical overview of promising nonthienopyridine antiplatelet agents. | 2008 Aug |
|
Pharmacology of emerging novel platelet inhibitors. | 2008 Aug |
|
Antiplatelet therapy in acute coronary syndromes. | 2008 Jul |
|
New antiplatelet therapies in development. | 2008 Jul 1 |
|
Multiple electrode aggregometry and P2Y(12) antagonists. | 2008 Jun |
|
GPR17: molecular modeling and dynamics studies of the 3-D structure and purinergic ligand binding features in comparison with P2Y receptors. | 2008 Jun 4 |
|
The active metabolite of prasugrel effectively blocks the platelet P2Y12 receptor and inhibits procoagulant and pro-inflammatory platelet responses. | 2008 Mar |
|
Coronary atherothrombotic disease: progress in antiplatelet therapy. | 2008 May |
|
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.
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:48:45 GMT 2023
by
admin
on
Fri Dec 15 15:48:45 GMT 2023
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Record UNII |
2144G00Y7W
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Record Status |
Validated (UNII)
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Record Version |
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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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