TICAGRELOR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H28F2N6O4S
Molecular Weight	522.568
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCSC1=NC(N[C@@H]2C[C@H]2C3=CC(F)=C(F)C=C3)=C4N=NN([C@@H]5C[C@H](OCCO)[C@@H](O)[C@H]5O)C4=N1

InChI

InChIKey=OEKWJQXRCDYSHL-FNOIDJSQSA-N

InChI=1S/C23H28F2N6O4S/c1-2-7-36-23-27-21(26-15-9-12(15)11-3-4-13(24)14(25)8-11)18-22(28-23)31(30-29-18)16-10-17(35-6-5-32)20(34)19(16)33/h3-4,8,12,15-17,19-20,32-34H,2,5-7,9-10H2,1H3,(H,26,27,28)/t12-,15+,16+,17-,19-,20+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C23H28F2N6O4S
Molecular Weight	522.568
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	6 / 6
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022433s015lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.ema.europa.eu/docs/en_GB/document_library/PIP_decision/WC500123240.pdf; http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/002303/WC500100562.pdf; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000PharmR.pdf

Ticagrelor (known trade names Brilinta, Brilique and Possia) is a P2Y12 platelet inhibitor. Brilinta has been approved by the US Food and Drug administration (FDA) in 2011 and is indicated to reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction. Brilinta also reduces the rate of stent thrombosis in patients who have been stented for treatment of ACS. Ticagrelor and its major metabolite reversibly interact with the platelet P2Y12 ADP-receptor to prevent signal transduction and platelet activation. Ticagrelor and its active metabolite are approximately equipotent. In vitro metabolism studies demonstrate that ticagrelor and its major active metabolite are weak inhibitors of CYP3A4, potential activators of CYP3A5 and inhibitors of the P-gp transporter. Most common adverse reactions are bleeding 12% and dyspnea 14%.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Purinergic receptor P2Y12 23 Target ID: CHEMBL2001 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022433s015lbl.pdf	Antagonist 2849

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute coronary syndrome 33 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022433s015lbl.pdf	Secondary		Approved 8583	BRILINTA Approved Use Indicated to reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction (MI). For at least the first 12 months following ACS, it is superior to clopidogrel. Reduces the rate of stent thrombosis in patients who have been stented for treatment of ACS. Launch Date 2011
Myocardial infarction 125 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022433s015lbl.pdf	Secondary		Approved 8583	BRILINTA Approved Use Indicated to reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction (MI). For at least the first 12 months following ACS, it is superior to clopidogrel. Reduces the rate of stent thrombosis in patients who have been stented for treatment of ACS. Launch Date 2011

C_max

Value	Dose	Analyte	Population
1208 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01898442	270 mg single, oral dose: 270 mg route of administration: oral experiment type: single co-administered:	TICAGRELOR plasma	Homo sapiens
1208 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01898442	360 mg single, oral dose: 360 mg route of administration: oral experiment type: single co-administered:	TICAGRELOR plasma	Homo sapiens
1583 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20642549/	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TICAGRELOR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
12379 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01898442	270 mg single, oral dose: 270 mg route of administration: oral experiment type: single co-administered:	TICAGRELOR plasma	Homo sapiens
12381 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01898442	360 mg single, oral dose: 360 mg route of administration: oral experiment type: single co-administered:	TICAGRELOR plasma	Homo sapiens
10160 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20642549/	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TICAGRELOR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
7 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022433s028lbl.pdf	90 mg single, oral dose: 90 mg route of administration: Oral experiment type: SINGLE co-administered:		TICAGRELOR plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022433s028lbl.pdf	90 mg single, oral dose: 90 mg route of administration: Oral experiment type: SINGLE co-administered:		TICAGRELOR plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1260 mg single, oral Highest studied dose Dose: 1260 mg Route: oral Route: single Dose: 1260 mg Sources: https://pubmed.ncbi.nlm.nih.gov/24040849 https://www.google.ru/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwji45rs27fuAhVmiYsKHW3hA2MQFjAGegQICBAC&url=https%3A%2F%2Fwww.tga.gov.au%2Ffile%2F797%2Fdownload&usg=AOvVaw3STEHV1bh8A3ZobpKVV1Gj	healthy Health Status: healthy Sources: https://pubmed.ncbi.nlm.nih.gov/24040849 https://www.google.ru/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwji45rs27fuAhVmiYsKHW3hA2MQFjAGegQICBAC&url=https%3A%2F%2Fwww.tga.gov.au%2Ffile%2F797%2Fdownload&usg=AOvVaw3STEHV1bh8A3ZobpKVV1Gj	DLT: Gastrointestinal disorder NOS, Sinus arrest... Dose limiting toxicities: Gastrointestinal disorder NOS (50%) Sinus arrest (serious, 16.7%) High grade atrioventricular block (serious, 16.7%) Ventricular escape rhythm (serious, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/24040849 https://www.google.ru/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwji45rs27fuAhVmiYsKHW3hA2MQFjAGegQICBAC&url=https%3A%2F%2Fwww.tga.gov.au%2Ffile%2F797%2Fdownload&usg=AOvVaw3STEHV1bh8A3ZobpKVV1Gj
900 mg single, oral MTD Dose: 900 mg Route: oral Route: single Dose: 900 mg Sources: https://pubmed.ncbi.nlm.nih.gov/24040849 https://www.google.ru/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwji45rs27fuAhVmiYsKHW3hA2MQFjAGegQICBAC&url=https%3A%2F%2Fwww.tga.gov.au%2Ffile%2F797%2Fdownload&usg=AOvVaw3STEHV1bh8A3ZobpKVV1Gj	healthy Health Status: healthy Sources: https://pubmed.ncbi.nlm.nih.gov/24040849 https://www.google.ru/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwji45rs27fuAhVmiYsKHW3hA2MQFjAGegQICBAC&url=https%3A%2F%2Fwww.tga.gov.au%2Ffile%2F797%2Fdownload&usg=AOvVaw3STEHV1bh8A3ZobpKVV1Gj	Sources: https://pubmed.ncbi.nlm.nih.gov/24040849 https://www.google.ru/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwji45rs27fuAhVmiYsKHW3hA2MQFjAGegQICBAC&url=https%3A%2F%2Fwww.tga.gov.au%2Ffile%2F797%2Fdownload&usg=AOvVaw3STEHV1bh8A3ZobpKVV1Gj
90 mg 2 times / day multiple, oral Recommended Dose: 90 mg, 2 times / day Route: oral Route: multiple Dose: 90 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022433s020lbl.pdf	unhealthy Health Status: unhealthy Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022433s020lbl.pdf	Disc. AE: Dyspnea... AEs leading to discontinuation/dose reduction: Dyspnea (0.9%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022433s020lbl.pdf
90 mg 2 times / day multiple, oral Recommended Dose: 90 mg, 2 times / day Route: oral Route: multiple Dose: 90 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022433s020lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022433s020lbl.pdf	Disc. AE: Bleeding... AEs leading to discontinuation/dose reduction: Bleeding (grade 3-5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022433s020lbl.pdf

AEs

AE	Significance	Dose	Population
Gastrointestinal disorder NOS	50% DLT	1260 mg single, oral Highest studied dose Dose: 1260 mg Route: oral Route: single Dose: 1260 mg Sources: https://pubmed.ncbi.nlm.nih.gov/24040849 https://www.google.ru/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwji45rs27fuAhVmiYsKHW3hA2MQFjAGegQICBAC&url=https%3A%2F%2Fwww.tga.gov.au%2Ffile%2F797%2Fdownload&usg=AOvVaw3STEHV1bh8A3ZobpKVV1Gj	healthy Health Status: healthy Sources: https://pubmed.ncbi.nlm.nih.gov/24040849 https://www.google.ru/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwji45rs27fuAhVmiYsKHW3hA2MQFjAGegQICBAC&url=https%3A%2F%2Fwww.tga.gov.au%2Ffile%2F797%2Fdownload&usg=AOvVaw3STEHV1bh8A3ZobpKVV1Gj
High grade atrioventricular block	serious, 16.7% DLT	1260 mg single, oral Highest studied dose Dose: 1260 mg Route: oral Route: single Dose: 1260 mg Sources: https://pubmed.ncbi.nlm.nih.gov/24040849 https://www.google.ru/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwji45rs27fuAhVmiYsKHW3hA2MQFjAGegQICBAC&url=https%3A%2F%2Fwww.tga.gov.au%2Ffile%2F797%2Fdownload&usg=AOvVaw3STEHV1bh8A3ZobpKVV1Gj	healthy Health Status: healthy Sources: https://pubmed.ncbi.nlm.nih.gov/24040849 https://www.google.ru/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwji45rs27fuAhVmiYsKHW3hA2MQFjAGegQICBAC&url=https%3A%2F%2Fwww.tga.gov.au%2Ffile%2F797%2Fdownload&usg=AOvVaw3STEHV1bh8A3ZobpKVV1Gj
Sinus arrest	serious, 16.7% DLT	1260 mg single, oral Highest studied dose Dose: 1260 mg Route: oral Route: single Dose: 1260 mg Sources: https://pubmed.ncbi.nlm.nih.gov/24040849 https://www.google.ru/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwji45rs27fuAhVmiYsKHW3hA2MQFjAGegQICBAC&url=https%3A%2F%2Fwww.tga.gov.au%2Ffile%2F797%2Fdownload&usg=AOvVaw3STEHV1bh8A3ZobpKVV1Gj	healthy Health Status: healthy Sources: https://pubmed.ncbi.nlm.nih.gov/24040849 https://www.google.ru/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwji45rs27fuAhVmiYsKHW3hA2MQFjAGegQICBAC&url=https%3A%2F%2Fwww.tga.gov.au%2Ffile%2F797%2Fdownload&usg=AOvVaw3STEHV1bh8A3ZobpKVV1Gj
Ventricular escape rhythm	serious, 16.7% DLT	1260 mg single, oral Highest studied dose Dose: 1260 mg Route: oral Route: single Dose: 1260 mg Sources: https://pubmed.ncbi.nlm.nih.gov/24040849 https://www.google.ru/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwji45rs27fuAhVmiYsKHW3hA2MQFjAGegQICBAC&url=https%3A%2F%2Fwww.tga.gov.au%2Ffile%2F797%2Fdownload&usg=AOvVaw3STEHV1bh8A3ZobpKVV1Gj	healthy Health Status: healthy Sources: https://pubmed.ncbi.nlm.nih.gov/24040849 https://www.google.ru/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwji45rs27fuAhVmiYsKHW3hA2MQFjAGegQICBAC&url=https%3A%2F%2Fwww.tga.gov.au%2Ffile%2F797%2Fdownload&usg=AOvVaw3STEHV1bh8A3ZobpKVV1Gj
Dyspnea	0.9% Disc. AE	90 mg 2 times / day multiple, oral Recommended Dose: 90 mg, 2 times / day Route: oral Route: multiple Dose: 90 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022433s020lbl.pdf	unhealthy Health Status: unhealthy Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022433s020lbl.pdf
Bleeding	grade 3-5 Disc. AE	90 mg 2 times / day multiple, oral Recommended Dose: 90 mg, 2 times / day Route: oral Route: multiple Dose: 90 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022433s020lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022433s020lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252 inducer 1087	substrate 1193 inhibitor 2438 inducer 440	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Cav1.2 58 Nav1.5 116 Kv1.5 27 Cav3.2 12 CYP3A5 136 CYP1A2 2153 CYP2B6 926 CYP2C8 1057 CYP2C19 2057 CYP2E1 1060 P-gp 1741 OAT3 747 OAT1 725 UGT1A1 246 L-type Ca channels 9	CYP3A5 446 CYP1A2 1197 CYP2A6 626 CYP2B6 776 CYP2C19 1119 P-gp 2052	CYP1A1 151 CYP1A2 832 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=13 Page: 13.0	likely
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=13 Page: 13.0	likely	AR-C124910XX 3
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=12 Page: 12-13	likely
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=12 Page: 12-13	likely	AR-C124910XX 3
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, Page: 9-11	moderate [IC50 10.5 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, Page: 9-11	moderate [IC50 11.7 uM]	AR-C124910XX 3
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, Page: 9-11	moderate [IC50 26.7 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=127 Page: 9-11, (PMDA) 127	moderate [IC50 33 uM]	AR-C124910XX 3
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=127 Page: 9-11, (PMDA) 127	moderate [IC50 43 uM]	AR-C124910XX 3
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, Page: 9-11	moderate [IC50 6.9 uM]	AR-C124910XX 3	no (co-administration study) Comment: Human liver microsomes, dicrofenac (substrate); Co-administration of ticagrelor (180 mg BID x 9 days) did not alter the systemic exposure of tolbutamide (500 mg QD on Day 5, CYP2C9 substrate) (GM ratio of AUCinf and Cmax were 103%, 110%, while 4-OH tolbutamide AUCinf GM ratio and Cmax GM ratio were 94% and 90%). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, Page: 9-11
CYP3A5 201	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=130 Page: 9-12, (PMDA) 130	moderate [IC50 7.6 uM]	AR-C124910XX 3
CYP3A5 201	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=60, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=66, https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=130 Page: 9-12, 60-61, 66-67, (PMDA) 130	moderate [IC50 8.2 uM]		yes (co-administration study) Comment: Human liver microsomes, midazolam (4-hydroxylation, substrate), no time-dependent inhibition; Co-administration of ticagrelor (270 mg AM + 180 mg PM on Day1, 180 mg BID on Days 2-7) significantly increased simvastatin (80 mg on Day 5, CYP3A4/5 substrate) AUCinf by 56% and Cmax 81%, and simvastatin acid AUCinf by 52% and Cmax by 64%. Co-administration of ticagrelor (270 mg AM + 180 mg PM on Day1, 180 mg BID on Days 2-7) significantly reduced oral midazolam (7.5 mg AM on Days 1 & 7) AUCinf by 10%, and 4’-OH-midazolam by 42%. Co-administration of ticagrelor (270 mg AM + 180 mg PM on Day 1, 180 mg BID on Days 2-7) does not alter the systemic exposure of IV midazolam (2.5 mg IV over 2 min AM on Days 1 & 7) and significantly reduced 4’-OH- midazolam systemic exposure by ~ 23%. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=60, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=66, https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=130 Page: 9-12, 60-61, 66-67, (PMDA) 130
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=127 Page: 9-12, (PMDA) 127	no [IC50 40 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, Page: 9-11	no [IC50 >50 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, Page: 9-11	no [IC50 >50 uM]	AR-C124910XX 3
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, Page: 9-11	no [IC50 >50 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=127 Page: 9-11, (PMDA) 127	no [IC50 >50 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, Page: 9-11	no [IC50 >50 uM]	AR-C124910XX 3
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, Page: 9-11	no [IC50 >50 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=62, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=64, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=66, https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=124, https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=130 Page: 9-12, 62-63, 64-65, 66-67 (PMDA) 124-125, 130	no [IC50 >50 uM]		weak (co-administration study) Comment: Human liver microsomes, midazolam (1-hydroxylation, substrate), midazolam 1-hydroxylation was activated in the presence of Cyt-b5 by 144.9% (CYP3A4 (cDNA expressed enzyme):Cyp-b5 = 1: 3 + 5.56 mcM ticagrelor), no time-dependent inhibition; Inhibited testosterone intrinsic clearance (IC50 = 23 mcM, pooled human liver microsomes (33 male and female donors); Co-administration of ticagrelor (270 mg AM + 90 mg PM on Day 1, 90 mg BID on Days 2-7) significantly increased atorvastatin (80 mg QD on Day 5) AUCinf 36% and Cmax 23%, atorvastatin lactone AUCinf 32% and Cmax 39%, s 2-OH atorvastatin AUCinf 33% and Cmax 13%, and 4-OH atorvastatin AUCinf 67% and Cmax 55%. Co-administration of ticagrelor (90 mg BID x 21 days) significantly increased ethinyl estradiol AUCinf, Cmax, and Cmin by 20%, 30.6%, and 20.2%, respectively. Co-administration of ticagrelor does not alter the systemic exposure of levonorgestrel. Co-administration of ticagrelor (270 mg AM + 180 mg PM on Day1, 180 mg BID on Days 2-7) significantly reduced oral midazolam (7.5 mg AM on Days 1 & 7) AUCinf by 10%, but did not alter 1’-OH- midazolam AUC. Co-administration of ticagrelor (270 mg AM + 180 mg PM on Day 1, 180 mg BID on Days 2-7) did not alter the systemic exposure of IV midazolam (2.5 mg IV over 2 min AM on Days 1 & 7) and 1’-OH-midazolam. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=62, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=64, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=66, https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=124, https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=130 Page: 9-12, 62-63, 64-65, 66-67 (PMDA) 124-125, 130
CYP1A1 272	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=14, https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=139 Page: 14, (PMDA) 139	no
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=12 Page: 12-13	no
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=12 Page: 12-13	no	AR-C124910XX 3
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=12 Page: 12-13	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=12 Page: 12-13	no	AR-C124910XX 3
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=9, https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=130 Page: 9-12, (PMDA) 130	no	AR-C124910XX 3
OAT1 730	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=160 Page: (PMDA) 160-161	no
OAT1 730	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=160 Page: (PMDA) 160-161	no	AR-C133913XX 3
OAT3 749	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=160 Page: (PMDA) 160-161	strong [Ki 13.4 uM]	AR-C133913XX 3
OAT3 749	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=160 Page: (PMDA) 160-161	strong [Ki 16.3 uM]	AR-C124910XX 3
OAT3 749	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=160 Page: (PMDA) 160-161	strong [Ki 4.9 uM]
OAT1 730	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=160 Page: (PMDA) 160-161	strong	AR-C124910XX 3
L-type Ca channels 9	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000PharmR.pdf#page=116 Page: 116.0	weak
L-type Ca channels 9	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000PharmR.pdf#page=116 Page: 116.0	weak	AR-C124910XX 3
UGT1A1 303	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000PharmR.pdf#page=117 Page: 26, 117	yes [IC50 0.759 uM]	AR-C124910XX 3
UGT1A1 303	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000PharmR.pdf#page=117 Page: 26, 117	yes [IC50 1 uM]
Kv1.5 42	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000PharmR.pdf#page=117 Page: 117.0	yes [IC50 10 uM]
Kv1.5 42	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000PharmR.pdf#page=117 Page: 117.0	yes [IC50 16.9 uM]	AR-C124910XX 3
Cav3.2 12	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000PharmR.pdf#page=117 Page: 117.0	yes [IC50 19.2 uM]
Cav3.2 12	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000PharmR.pdf#page=117 Page: 117.0	yes [IC50 19.9 uM]	AR-C124910XX 3
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=4, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=58, https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=157 Page: 4-5, 58-59 (PMDA) 157	yes [IC50 7.8 uM]		yes (co-administration study) Comment: MDR1-MDCK monolayer, H3-digoxin (5 mcM) as a substrate, Flux ratio = 19.5 (digoxin only), 3.1 (digoxin + 10 mcM Ticagrelor); Co-administration of ticagrelor (400 mg QD, Days 1-16) significantly increased digoxin (0.25 mg BID on Day 6, 0.25 mg QD on Days 7-14, P-gp substrate) AUC0-72, Css,max, and Css, min by 28%, 75% and 31%, respectively. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=4, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=58, https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=157 Page: 4-5, 58-59 (PMDA) 157
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=4, https://www.pmda.go.jp/drugs/2016/P20161026001/670227000_22800AMX00680_I100_1.pdf#page=157 Page: 4-5, (PMDA) 157	yes [IC50 9.9 uM]	AR-C124910XX 3

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000PharmR.pdf#page=123, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=6, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=43 Page: 123, (ClinPharm) 5-6, 43-44, 45-47, 47-49	major [Km 11 uM]		yes (co-administration study) Comment: Human liver microsomes (determination of CYPs) and human cDNA expressed emzymes (Km for AR-C124910XX formation), Km (AR-C124910XX, human liver microsomes) = 27 mcM; Km (AR-C133913XX formation) = 41 mcM; Co-administration of ketoconazole (200 mg BID for 10 days, CYP3A4 inhibitor) significantly increased ticagrelor (90 mg QD on Day 4) AUCinf by 7.32 fold and Cmax by 2.35 fold, and decreased AR-C124910XX AUCinf by 56% and Cmax by 89%. Co-administration of diltiazem (240 mg QD x 14 days, moderate CYP3A4 inhibitor) significantly increased ticagrelor (90 mg QD on Day 8) AUCinf by 2.74 fold and Cmax by 1.69, and decreased AR-C124910XX AUCinf by 13% and Cmax by 38%. Co-administration of rifampin (600 mg QD Days 4-17, strong CYP3A4/P-gp inducer) significantly decreased ticagrelor (180 mg QD Days 1 & 15) AUCinf by 86% and Cmax by 73%, and decreased AR-C124910XX AUCinf by 46% and did not affect Cmax. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000PharmR.pdf#page=123, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=6, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=43 Page: 123, (ClinPharm) 5-6, 43-44, 45-47, 47-49
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP2A6 626	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP2B6 776	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP3A5 446	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000PharmR.pdf#page=123, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=6 Page: 123, (ClinPharm) 5-6	yes [Km 5.36 uM]
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=4 Page: 4.0	yes
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000ClinPharmR.pdf#page=4 Page: 4.0	yes	AR-C124910XX 3

Tox targets

Target	Modality	Metabolite
Cav1.2 63	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000PharmR.pdf#page=117 Page: 117.0
Cav1.2 63	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000PharmR.pdf#page=117 Page: 117.0	AR-C124910XX 3
Nav1.5 119	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000PharmR.pdf#page=117 Page: 117.0
Nav1.5 119	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000PharmR.pdf#page=117 Page: 117.0	AR-C124910XX 3
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000PharmR.pdf#page=119 Page: 119.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:68558	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:68558
ChemicalBook	CB51509134	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB51509134
eMolecules	36756307	https://www.emolecules.com/cgi-bin/more?vid=36756307
MolPort	MolPort-023-329-971	https://www.molport.com/shop/molecule-link/MolPort-023-329-971
Selleck Chemicals	ticagrelor	http://www.selleckchem.com/products/ticagrelor.html
ZINC	ZINC000028957444	http://zinc15.docking.org/substances/ZINC000028957444

PubMed

Title	Date	PubMed
Dyspnoea after AZD6140: safety first?	2006 Jun	16698878
P2Y12 receptor antagonists: a rapidly expanding group of antiplatelet agents.	2006 May	16569650
Aspirin and clopidogrel resistance: consideration and management.	2006 Oct	17020569
Platelet P2 receptors: old and new targets for antithrombotic drugs.	2007 Jan	17187456
Molecule of the month. Ticagrelor.	2007 May	17637939
Dyspnoea and antiplatelet agents: revisited.	2007 Sep	17686098
Optimizing platelet P2Y12 inhibition for patients undergoing PCI.	2007 Summer	17614940
Clinical overview of promising nonthienopyridine antiplatelet agents.	2008 Aug	18657683
Pharmacology of emerging novel platelet inhibitors.	2008 Aug	18657681
Platelet ADP-receptor antagonists for cardiovascular disease: past, present and future.	2008 Dec	18957959
Antiplatelet therapy in acute coronary syndromes.	2008 Jul	18611368
Gateways to clinical trials.	2008 Mar	18560631
Investigational antiplatelet drugs for the treatment and prevention of coronary artery disease.	2008 Sep-Oct	18708826
P2Y(12) inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use.	2009 Aug	19633016
Oral antiplatelet therapy for acute and chronic management of NSTE ACS: residual ischemic risk and opportunities for improvement.	2009 Dec	19890703
Ticagrelor versus clopidogrel in acute coronary syndromes.	2009 Dec 10	20050198
Ticagrelor versus clopidogrel in acute coronary syndromes.	2009 Dec 10	20050197
Ticagrelor versus clopidogrel in acute coronary syndromes.	2009 Dec 10	20050196
Ticagrelor versus clopidogrel in acute coronary syndromes.	2009 Dec 10	20007565
ACP Journal Club. Ticagrelor was more effective than clopidogrel, with no increase in major bleeding in acute coronary syndromes.	2009 Dec 15	20008753
Current problems, new opportunities and future directions of anti-platelet therapy - increasing role of novel antiplatelet agents in cardiovascular diseases.	2009 Jan	19149707
New P2Y12 blockers.	2009 Jul	19630813
Effect of blocking platelet activation with AZD6140 on development of abdominal aortic aneurysm in a rat aneurysmal model.	2009 Mar	19028049
Update on oral antiplatelet therapy: principles, problems and promises.	2009 May	19450051
HOTLINE I, PLATO favours ticagrelor over clopidogrel in ACS.	2009 Nov	19891080
P2Y12 inhibitors: thienopyridines and direct oral inhibitors.	2009 Nov	19882081
European Society of Cardiology--2009 annual congress. 31 August - 2 September 2009, Barcelona, Spain.	2009 Nov	19844849
Ticagrelor binds to human P2Y(12) independently from ADP but antagonizes ADP-induced receptor signaling and platelet aggregation.	2009 Sep	19552634
Ticagrelor--is there need for a new player in the antiplatelet-therapy field?	2009 Sep 10	19717845
Novel antiplatelet agents in development: prasugrel, ticagrelor, and cangrelor and beyond.	2009 Sep-Oct	19262362
Ticagrelor: the first reversibly binding oral P2Y12 receptor antagonist.	2009 Winter	19604248
The PLATO trial: do you believe in magic?	2010 Apr	20007979
Balancing the benefits and risks of antiplatelet agents in patients with non-ST-segment elevated acute coronary syndromes and undergoing percutaneous coronary intervention.	2010 Aug	20111983
Limitations of current therapies to prevent thrombosis: a need for novel strategies.	2010 Feb	20094648
The TRITON versus PLATO trials: differences beyond platelet inhibition.	2010 Feb	20024505
Pharmacokinetic, pharmacodynamic and clinical profile of novel antiplatelet drugs targeting vascular diseases.	2010 Feb 1	20050853
Recent advances in cardiology.	2010 Jan	20014984
Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study.	2010 Jan 23	20079528
PLATO study of ticagrelor versus clopidogrel in patients with high-risk acute coronary syndromes.	2010 Jul	20432073
The case for routine genotyping in dual-antiplatelet therapy.	2010 Jul 6	20471193
The novel P2Y 12 antagonist AZD6140 rapidly and reversibly reduces platelet activation in diabetic rats.	2010 Mar	19846210
Advances in antiplatelet treatment for acute coronary syndromes.	2010 May	19910292
Forecasting drug utilization and expenditure in a metropolitan health region.	2010 May 17	20478043

Patents

Sample Use Guides

In Vivo Use Guide

Initiate treatment with 180 mg (two 90 mg tablets) oral loading dose. Continue treatment with 90 mg twice daily.

Route of Administration: Oral

In Vitro Use Guide

In human liver microsomes, ticagrelor inhibited midazolam 4-hydroxylation with an IC50 of 8.2 uM. Evaluated in fresh human hepatocytes at concentration up to 20 uM, ticagrelor was not an inducer of CYP1A2 or CYP3A4.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:18:18 GMT 2025` Edited by `admin` on `Mon Mar 31 18:18:18 GMT 2025`
Record UNII	GLH0314RVC
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BRILINTA

Preferred Name

English

TICAGRELOR

Official Name

English

1,2-CYCLOPENTANEDIOL, 3-(7-(((1R,2S)-2-(3,4-DIFLUOROPHENYL)CYCLOPROPYL)AMINO)-5-(PROPYLTHIO)-3H-1,2,3-TRIAZOLO(4,5-D)PYRIMIDIN-3-YL)-5-(2-HYDROXYETHOXY)-, (1S,2S,3R,5S)-

Systematic Name

English

AZD-6140

Code

English

TICAGRELOR [MI]

Common Name

English

(1S,2S,3R,5S)-3-(7-((1R,2S)-2-(3,4-Difluorophenyl)cyclopropylamino)-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol

Systematic Name

English

POSSIA

Brand Name

English

TICAGRELOR [EMA EPAR]

Common Name

English

Ticagrelor [WHO-DD]

Common Name

English

TICAGRELOR [EP MONOGRAPH]

Common Name

English

TICAGRELOR [USAN]

Common Name

English

TICAGRELOR [ORANGE BOOK]

Common Name

English

ticagrelor [INN]

Common Name

English

TICAGRELOR [USP-RS]

Common Name

English

TICAGRELOR [JAN]

Common Name

English

TICAGRELOR [MART.]

Common Name

English

AZD6140

Code

English

BRILIQUE

Brand Name

English

AR-C126532XX

Code

English

TICAGRELOR [VANDF]

Common Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

POSSIA (WITHDRAWN: PERIPHERAL VASCULAR DISEASES)