ALISKIREN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C30H53N3O6
Molecular Weight	551.7583
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COCCCOC1=C(OC)C=CC(C[C@@H](C[C@H](N)[C@@H](O)C[C@@H](C(C)C)C(=O)NCC(C)(C)C(N)=O)C(C)C)=C1

InChI

InChIKey=UXOWGYHJODZGMF-QORCZRPOSA-N

InChI=1S/C30H53N3O6/c1-19(2)22(14-21-10-11-26(38-8)27(15-21)39-13-9-12-37-7)16-24(31)25(34)17-23(20(3)4)28(35)33-18-30(5,6)29(32)36/h10-11,15,19-20,22-25,34H,9,12-14,16-18,31H2,1-8H3,(H2,32,36)(H,33,35)/t22-,23-,24-,25-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021985s023lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/21687346

Aliskiren – the only direct renin inhibitor which is clinically used as an antihypertensive drug. Aliskiren is the first of a new class of antihypertensive agents. Aliskiren is a new renin inhibitor of a novel structural class that has recently been shown to be efficacious in hypertensive patients after once-daily oral dosing. In short-term studies, it was effective in lowering blood pressure either alone or in combination with valsartan and hydrochlorothiazide, and had a low incidence of serious adverse effects. It was approved by the Food and Drug Administration in 2007 for the use as a monotherapy or in combination with other antihypertensives. Aliskiren is marketed under the trade name Tekturna. Aliskiren effectively reduces functional plasma renin activity by binding to renin with high affinity, preventing it from converting angiotensinogen to angiotensin I. The inhibition of renin by aliskiren is associated with a reduction in circulating levels of angiotensin I and II, with a resultant increase in plasma renin concentration and inhibit activation of mitogen-activated protein kinases ERK1 (p44) and ERK2 (p42).

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Renin 7 Target ID: CHEMBL286 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021985s023lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/18611061	Inhibitor 8504		0.6 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 575 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021985s023lbl.pdf	Primary		Approved 8583	TEKTURNA Approved Use Amturnide is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including amlodipine and hydrochlorothiazide (HCTZ). There are no controlled trials demonstrating risk reduction with Amturnide. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than 1 drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality have also been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (e.g., patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. This fixed combination drug is not indicated for initial therapy of hypertension. Amturnide is a combination of aliskiren, a renin inhibitor, amlodipine besylate, a dihydropyridine calcium channel blocker, and hydrochlorothiazide (HCTZ), a thiazide diuretic. Amturnide is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions: Not indicated for initial therapy. (1) Launch Date 2007

C_max

Value	Dose	Analyte	Population
273 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01570686	300 mg 1 times / day steady, oral dose: 300 mg route of administration: oral experiment type: steady co-administered:	ALISKIREN plasma	Homo sapiens population: unhealthy age: sex: food status: Fasted
252 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01570686	300 mg 1 times / day steady, oral dose: 300 mg route of administration: oral experiment type: steady co-administered:	ALISKIREN plasma	Homo sapiens population: unhealthy age: sex: food status: Fasted
108 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01570686	300 mg 1 times / day steady, oral dose: 300 mg route of administration: oral experiment type: steady co-administered:	ALISKIREN plasma	Homo sapiens population: unhealthy age: sex: food status: Fed
102 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01570686	300 mg 1 times / day steady, oral dose: 300 mg route of administration: oral experiment type: steady co-administered:	ALISKIREN plasma	Homo sapiens population: unhealthy age: sex: food status: Fed
290.2 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/18611061/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	ALISKIREN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Analyte	Population
1580 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01570686	300 mg 1 times / day steady, oral dose: 300 mg route of administration: oral experiment type: steady co-administered:	ALISKIREN plasma	Homo sapiens population: unhealthy age: sex: food status: Fasted
1540 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01570686	300 mg 1 times / day steady, oral dose: 300 mg route of administration: oral experiment type: steady co-administered:	ALISKIREN plasma	Homo sapiens population: unhealthy age: sex: food status: Fasted
872 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01570686	300 mg 1 times / day steady, oral dose: 300 mg route of administration: oral experiment type: steady co-administered:	ALISKIREN plasma	Homo sapiens population: unhealthy age: sex: food status: Fed
1100 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01570686	300 mg 1 times / day steady, oral dose: 300 mg route of administration: oral experiment type: steady co-administered:	ALISKIREN plasma	Homo sapiens population: unhealthy age: sex: food status: Fed
1399 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/18611061/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	ALISKIREN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
41 h REVIEW https://pubmed.ncbi.nlm.nih.gov/18611061/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		ALISKIREN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Doses

Dose	Population	Adverse events
600 mg single, oral Highest studied dose Dose: 600 mg Route: oral Route: single Dose: 600 mg Sources: https://pubmed.ncbi.nlm.nih.gov/18538111	healthy, 18 - 45 Health Status: healthy Age Group: 18 - 45 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18538111	Sources: https://pubmed.ncbi.nlm.nih.gov/18538111
600 mg 1 times / day multiple, oral Highest studied dose Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17367658	unhealthy, 53 Health Status: unhealthy Age Group: 53 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/17367658	Disc. AE: Diarrhea... AEs leading to discontinuation/dose reduction: Diarrhea (0.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/17367658
300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021985s023lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021985s023lbl.pdf	Disc. AE: Disorder fetal, Angioedema... AEs leading to discontinuation/dose reduction: Disorder fetal Angioedema Angioedema Hypotension Impaired renal function Hyperkalemia Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021985s023lbl.pdf
150 mg 1 times / day steady, oral Dose: 150 mg, 1 times / day Route: oral Route: steady Dose: 150 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01437943	unhealthy Health Status: unhealthy Sources: https://clinicaltrials.gov/ct2/show/NCT01437943	Other AEs: GI bleed, Knee hemarthrosis... Other AEs: GI bleed (serious, 1 patient) Knee hemarthrosis (serious, 1 patient) Diarrhea (below serious, 5 patients) Lower extremities weakness of (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT01437943
300 mg 1 times / day steady, oral Dose: 300 mg, 1 times / day Route: oral Route: steady Dose: 300 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00768040	unhealthy Health Status: unhealthy Sources: https://clinicaltrials.gov/ct2/show/NCT00768040	Other AEs: Cellulitis, Pneumonia... Other AEs: Cellulitis (serious, 1 patient) Pneumonia (serious, 1 patient) Diabetic foot (serious, 1 patient) Choroidal neovascularisation (below serious, 1 patient) Foreign body sensation in eyes (below serious, 1 patient) Asteroid hyalosis (below serious, 1 patient) Retinal neovascularisation (below serious, 1 patient) Vision blurred (below serious, 1 patient) Vitreous detachment (below serious, 1 patient) Diarrhoea (below serious, 1 patient) Flatulence (below serious, 1 patient) Fatigue (below serious, 1 patient) Fungal skin infection (below serious, 1 patient) Respiratory tract infection (below serious, 1 patient) Sinusitis (below serious, 1 patient) Tooth fracture (below serious, 1 patient) Hypoglycaemia (below serious, 1 patient) Arthritis (below serious, 1 patient) Muscle spasms (below serious, 1 patient) Myalgia (below serious, 1 patient) Pain in extremity (below serious, 1 patient) Pain in jaw (below serious, 1 patient) Basal cell carcinoma (below serious, 2 patients) Paraesthesia (below serious, 1 patient) Epistaxis (below serious, 1 patient) Hypotension (below serious, 2 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00768040
300 mg 1 times / day steady, oral Dose: 300 mg, 1 times / day Route: oral Route: steady Dose: 300 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00894387	unhealthy Health Status: unhealthy Sources: https://clinicaltrials.gov/ct2/show/NCT00894387	Other AEs: Anaemia, Haemorrhagic disorder... Other AEs: Anaemia (serious, 6 patients) Haemorrhagic disorder (serious, 1 patient) Hilar lymphadenopathy (serious, 1 patient) Lymphadenopathy (serious, 1 patient) Splenic infarction (serious, 1 patient) Angina unstable (serious, 7 patients) Aortic valve incompetence (serious, 1 patient) Arteriospasm coronary (serious, 1 patient) Atrial flutter (serious, 3 patients) Atrioventricular block complete (serious, 2 patients) Cardio-respiratory arrest (serious, 7 patients) Cardiogenic shock (serious, 7 patients) Cardiomyopathy (serious, 1 patient) Cardiopulmonary failure (serious, 2 patients) Coronary artery disease (serious, 4 patients) Left ventricular dysfunction (serious, 1 patient) Low cardiac output syndrome (serious, 1 patient) Fibrosis myocardial (serious, 1 patient) Tachyarrhythmia (serious, 1 patient) Tachycardia (serious, 3 patients) Ventricular extrasystoles (serious, 1 patient) Ventricular tachycardia (serious, 10 patients) Vertigo (serious, 4 patients) Cataract (serious, 3 patients) Retinal detachment (serious, 1 patient) Constipation (serious, 2 patients) Duodenal ulcer haemorrhage (serious, 1 patient) Enterocolitis (serious, 1 patient) Gastritis (serious, 1 patient) Hiatus hernia (serious, 1 patient) Intestinal obstruction (serious, 1 patient) Intestinal polyp (serious, 1 patient) Nausea (serious, 8 patients) Small intestinal obstruction (serious, 1 patient) Umbilical hernia, obstructive (serious, 1 patient) Upper gastrointestinal haemorrhage (serious, 1 patient) Vomiting (serious, 5 patients) Chest discomfort (serious, 1 patient) Chest pain (serious, 6 patients) Device lead issue (serious, 1 patient) Drug intolerance (serious, 1 patient) Necrosis (serious, 1 patient) Non-cardiac chest pain (serious, 7 patients) Soft tissue inflammation (serious, 1 patient) Sudden death (serious, 9 patients) Cholecystitis (serious, 2 patients) Hepatic cirrhosis (serious, 1 patient) Hepatic cyst (serious, 1 patient) Hepatorenal syndrome (serious, 1 patient) Heart transplant rejection (serious, 1 patient) Anal abscess (serious, 1 patient) Appendicitis (serious, 2 patients) Bronchitis bacterial (serious, 1 patient) Erysipelas (serious, 2 patients) Gastrointestinal viral infection (serious, 1 patient) Hepatitis B (serious, 1 patient) Liver abscess (serious, 1 patient) Infection localised (serious, 1 patient) Lower respiratory tract infection (serious, 3 patients) Orchitis (serious, 1 patient) Osteomyelitis acute (serious, 1 patient) Paronychia (serious, 1 patient) Pseudomembranous colitis (serious, 2 patients) Respiratory tract infection (serious, 3 patients) Sepsis (serious, 8 patients) Viral infection (serious, 1 patient) Wound infection pseudomonas (serious, 1 patient) Accidental overdose (serious, 1 patient) Ankle fracture (serious, 1 patient) Contusion (serious, 1 patient) Dermatitis artefacta (serious, 1 patient) Electric shock (serious, 1 patient) Extradural haematoma (serious, 1 patient) Femoral neck fracture (serious, 1 patient) Femur fracture (serious, 4 patients) Head injury (serious, 1 patient) Humerus fracture (serious, 2 patients) Laceration (serious, 1 patient) Post procedural haematoma (serious, 1 patient) Procedural haemorrhage (serious, 1 patient) Pubis fracture (serious, 1 patient) Spinal compression fracture (serious, 1 patient) Splenic rupture (serious, 1 patient) Subdural haematoma (serious, 2 patients) Thermal burn (serious, 1 patient) Toxicity to various agents (serious, 2 patients) Blood creatinine increased (serious, 3 patients) Haemoglobin decreased (serious, 1 patient) International normalised ratio increased (serious, 2 patients) Renal function test abnormal (serious, 1 patient) Decreased appetite (serious, 1 patient) Diabetic ketoacidosis (serious, 1 patient) Failure to thrive (serious, 1 patient) Fluid intake reduced (serious, 1 patient) Hypoglycaemia (serious, 7 patients) Arthralgia (serious, 1 patient) Arthritis (serious, 1 patient) Bursitis (serious, 1 patient) Costochondritis (serious, 1 patient) Joint effusion (serious, 1 patient) Muscular weakness (serious, 1 patient) Pain in extremity (serious, 2 patients) Bladder neoplasm (serious, 1 patient) Colon cancer (serious, 2 patients) Colorectal cancer (serious, 1 patient) Hepatic neoplasm (serious, 1 patient) Hepatobiliary neoplasm (serious, 1 patient) Adenocarcinoma lung (serious, 1 patient) Lung neoplasm malignant (serious, 1 patient) Lung squamous cell carcinoma stage unspecified (serious, 1 patient) Multiple myeloma (serious, 1 patient) Prostate cancer metastatic (serious, 1 patient) Uterine leiomyoma (serious, 1 patient) Anterior spinal artery syndrome (serious, 1 patient) Burning sensation (serious, 1 patient) Cerebral haematoma (serious, 1 patient) Coma (serious, 1 patient) Diabetic neuropathy (serious, 1 patient) Dizziness (serious, 4 patients) Dysarthria (serious, 1 patient) Embolic stroke (serious, 2 patients) Epilepsy (serious, 2 patients) Haemorrhagic stroke (serious, 1 patient) Intracranial haematoma (serious, 1 patient) Loss of consciousness (serious, 1 patient) Metabolic encephalopathy (serious, 1 patient) Myasthenia gravis (serious, 1 patient) Myasthenia gravis crisis (serious, 1 patient) Neuropathy peripheral (serious, 1 patient) Somnolence (serious, 2 patients) Trigeminal neuralgia (serious, 1 patient) Unresponsive to stimuli (serious, 1 patient) Uraemic encephalopathy (serious, 1 patient) Abnormal behaviour (serious, 1 patient) Alcohol abuse (serious, 1 patient) Anxiety (serious, 1 patient) Confusional state (serious, 2 patients) Depression suicidal (serious, 1 patient) Screaming (serious, 1 patient) Bladder tamponade (serious, 1 patient) Haematuria (serious, 1 patient) Nephropathy (serious, 1 patient) Polyuria (serious, 1 patient) Renal artery stenosis (serious, 1 patient) Renal failure acute (serious, 20 patients) Renal impairment (serious, 5 patients) Benign prostatic hyperplasia (serious, 2 patients) Menorrhagia (serious, 1 patient) Acute pulmonary oedema (serious, 7 patients) Acute respiratory distress syndrome (serious, 1 patient) Acute respiratory failure (serious, 2 patients) Asthma (serious, 1 patient) Atelectasis (serious, 1 patient) Bronchiectasis (serious, 1 patient) Chronic obstructive pulmonary disease (serious, 13 patients) Dyspnoea (serious, 20 patients) Pneumonitis (serious, 1 patient) Pneumothorax (serious, 1 patient) Productive cough (serious, 1 patient) Pulmonary artery thrombosis (serious, 1 patient) Respiratory failure (serious, 6 patients) Wheezing (serious, 1 patient) Hyperhidrosis (serious, 2 patients) Skin ulcer (serious, 1 patient) Skin ulcer haemorrhage (serious, 1 patient) Extremity necrosis (serious, 1 patient) Hypotension (serious, 24 patients) Peripheral arterial occlusive disease (serious, 4 patients) Peripheral ischaemia (serious, 1 patient) Disorder peripheral vascular (serious, 2 patients) Phlebitis (serious, 1 patient) Diarrhoea (below serious, 49 patients) Hyperkalaemia (below serious, 155 patients) Renal impairment (below serious, 47 patients) Cough (below serious, 59 patients) Hypotension (below serious, 117 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00894387
300 mg 1 times / day steady, oral Dose: 300 mg, 1 times / day Route: oral Route: steady Dose: 300 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00982033	unhealthy Health Status: unhealthy Sources: https://clinicaltrials.gov/ct2/show/NCT00982033	Other AEs: Thrush NOS... Other AEs: Thrush NOS (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT00982033
300 mg 1 times / day steady, oral Dose: 300 mg, 1 times / day Route: oral Route: steady Dose: 300 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01417104	unhealthy Health Status: unhealthy Sources: https://clinicaltrials.gov/ct2/show/NCT01417104	Other AEs: Hyperkalemia... Other AEs: Hyperkalemia (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT01417104

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	inhibitor 2438	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2C8 1057 CYP2C19 2057 CYP2E1 1060 CYP3A4/5 296 BCRP 910 P-gp 1741	P-gp 2052 OATP1 3 OCT1 393 OCT3 92 MRP2 252 BCRP 697	CYP 74

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_ClinPharmR_P2.pdf Page: 12.0	no [Inhibition 100 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_ClinPharmR_P2.pdf Page: 12.0	no [Inhibition 100 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_ClinPharmR_P2.pdf Page: 12.0	no [Inhibition 100 uM]
CYP3A4/5 357	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_ClinPharmR_P2.pdf Page: 12.0	no [Inhibition 100 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_PharmR_P1.pdf Page: 46.0	no [Inhibition 200 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_PharmR_P1.pdf Page: 46.0	no [Inhibition 200 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_PharmR_P1.pdf Page: 46.0	no [Inhibition 200 uM]
CYP 150	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_ClinPharmR_P4.pdf Page: 47.0	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_ClinPharmR_P2.pdf Page: 21.0	no
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_ClinPharmR_P1.pdf Page: 30.0	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
OATP1 3	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_ClinPharmR_P1.pdf Page: 30, 57	inconclusive
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_ClinPharmR_P1.pdf Page: 30.0	major	yes (co-administration study) Comment: itraconazole increased Cmax by 5-fold and AUC by 6-fold; ketaconazole increased Cmax a nd AUC by 2-fold; cyclosporine increased Cmax by 5-fold and AUC by 3-fold Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_ClinPharmR_P1.pdf Page: 30.0
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_ClinPharmR_P1.pdf Page: 30, 55, 56	minor
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_ClinPharmR_P1.pdf Page: 31.0	no
MRP2 252	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_ClinPharmR_P1.pdf Page: 31.0	no
OCT1 393	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_ClinPharmR_P1.pdf Page: 31, 57	no
OCT3 92	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_ClinPharmR_P1.pdf Page: 31, 57	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_ClinPharmR_P1.pdf Page: 31.0	yes	yes (co-administration study) Comment: from clinical pharmacology review pdf 4: ketaconazole increased Cmax by 81% and AUC by 76%; from product label: itraconazole increased Cmax by 5-fold and AUC by 6-fold; cyclosporine increased Cmax by 5-fold and AUC by 3-fold Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_ClinPharmR_P1.pdf Page: 31.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021985s000_PharmR_P1.pdf Page: 46, 69

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:601027	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:601027
ChemicalBook	CB9966226	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9966226
eMolecules	31229123	https://www.emolecules.com/cgi-bin/more?vid=31229123
MolPort	MolPort-006-167-755	https://www.molport.com/shop/molecule-link/MolPort-006-167-755
MolPort	MolPort-028-956-725	https://www.molport.com/shop/molecule-link/MolPort-028-956-725
ZINC	ZINC000004393164	http://zinc15.docking.org/substances/ZINC000004393164

PubMed

Title	Date	PubMed
Aliskiren, a novel oral renin inhibitor, provides dose-dependent efficacy and placebo-like tolerability in Japanese patients with hypertension.	2006 Dec	17378372
Opportunities for structure-based design of protease-directed drugs.	2006 Dec	17112720
[Renin-angiotensin system].	2006 Jul	16895166
[Antihypertensive drugs in clinical development].	2006 May	16819244
Aliskiren: a renin inhibitor offering a new approach for the treatment of hypertension.	2006 Oct	16989601
New drugs for hypertension: what do they offer?	2006 Oct	16965731
Prorenin induces intracellular signaling in cardiomyocytes independently of angiotensin II.	2006 Oct	16940215
Molecule of the Month. Aliskiren fumarate.	2006 Sep	17080206
Imaging the renin-angiotensin system: an important target of anti-hypertensive therapy.	2006 Sep 15	16979787
Antihypertensive therapies.	2007 Aug	17821828
[The best of hypertension in 2006].	2007 Jan	17405564
Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial.	2007 Jul 21	17658393
Dual inhibition of the renin system by aliskiren and valsartan.	2007 Jul 21	17658374
Low-dose renin inhibitor and low-dose AT(1)-receptor blocker therapy ameliorate target-organ damage in rats harbouring human renin and angiotensinogen genes.	2007 Jun	17703434
Aliskiren for renin inhibition: a new class of antihypertensives.	2007 Mar	17341529
Identification of hot spots within druggable binding regions by computational solvent mapping of proteins.	2007 Mar 22	17305325
The difficult conception, birth and delivery of a renin inhibitor: controversies around aliskiren.	2007 Sep	17762637
Inhibition of renin: an updated review of the development of renin inhibitors.	2007 Sep	17729187

Patents

Sample Use Guides

In Vivo Use Guide

Starting dose: 150 mg once daily with a routine pattern with regard to meals. If blood pressure remains uncontrolled titrate up to 300 mg daily (2.1, 2.3) Majority of effect of given dose attained in 2 weeks

Route of Administration: Oral

In Vitro Use Guide

Aliskiren (0.1 or 10 uM) dose-dependently improved functions and increased both VEGF and stromal cell-derived factor-1α (SDF-1α) expression of EPCs from patients with T2DM or EPCs from healthy volunteers and treated with high glucose.

Name

Type

Language

ALISKIREN

Official Name

English

SPP-100

Preferred Name

English

aliskiren [INN]

Common Name

English

ALISKIREN [USAN]

Common Name

English

Aliskiren [WHO-DD]

Common Name

English

ALISKIREN [EMA EPAR]

Common Name

English

(2S,4S,5S,7S)-5-Amino-N-(2-carbamoyl-2-methylpropyl)-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnonamide

Systematic Name

English

SPP100

Code

English

ALISKIREN [MI]

Common Name

English

ALISKIREN [HSDB]

Common Name

English

ALISKIREN [VANDF]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175900