Aliskiren

Summary

Aliskiren (CHEMBL1639) is an approved small-molecule antihypertensive agent (ATC C09XA02) targeting REN; indicated across 18 conditions including cardiovascular disorder and hypertensive disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C09XA02
• Targets: 1 (REN)
• Indications: 18 conditions
• Clinical trials: 146
• Chemistry: 551.8 Da · C30H53N3O6

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1639
Name	Aliskiren
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5493444
ChEBI	CHEBI:601027
ATC	C09XA02
Molecular formula	C30H53N3O6
Molecular weight	551.8
InChIKey	UXOWGYHJODZGMF-QORCZRPOSA-N

SMILES: CC(C)[C@@H](CC1=CC(=C(C=C1)OC)OCCCOC)C[C@@H]([C@H](C[C@@H](C(C)C)C(=O)NCC(C)(C)C(=O)N)O)N

IUPAC name: (2S,4S,5S,7S)-5-amino-N-(3-amino-2,2-dimethyl-3-oxopropyl)-4-hydroxy-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-8-methyl-2-propan-2-ylnonanamide

ChEBI definition: A monomethoxybenzene compound having a 3-methoxypropoxy group at the 2-position and a multi-substituted branched alkyl substituent at the 4-position.

Pharmacological roles (ChEBI): antihypertensive agent.

Also known as: Aliskiren, Aliskirene, Aliskireno, Rasilez, SPP-100, SPP100, aliskiren, Aliskerin, ALISKIREN, SID174006809, ALISKIREN HEMIFUMARATE

Parent form; salt/anhydrous children: CHEMBL1667, CHEMBL559358, CHEMBL3508698, CHEMBL3545059

Patent coverage: 399 distinct patent families (1,033 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,026 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
REN	renin	Inhibition	9.2	0.2%	P00797

Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: Renin, Renin, Renin-1, Renin.

Bioactivity

ChEMBL activities: 29 potent at pChembl ≥ 5 of 29 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
REN	9.4	IC50	0.4	nM	CHEMBL_ACT_10866108
REN	9.3	IC50	0.5	nM	CHEMBL_ACT_2625946
REN	9.28	IC50	0.53	nM	CHEMBL_ACT_10866101
REN	9.28	IC50	0.53	nM	CHEMBL_ACT_3076309
REN	9.22	IC50	0.6	nM	CHEMBL_ACT_12063305
REN	9.22	IC50	0.6	nM	CHEMBL_ACT_15165246
REN	9.22	IC50	0.6	nM	CHEMBL_ACT_18255685
REN	9.22	IC50	0.6	nM	CHEMBL_ACT_24860347
REN	9.22	IC50	0.6	nM	CHEMBL_ACT_24860349
REN	9.22	IC50	0.6	nM	CHEMBL_ACT_2625944
REN	9.22	IC50	0.6	nM	CHEMBL_ACT_2639499
REN	9.22	IC50	0.6	nM	CHEMBL_ACT_2723731
REN	9.22	IC50	0.6	nM	CHEMBL_ACT_2723732
REN	9.22	IC50	0.6	nM	CHEMBL_ACT_3550773
REN	9.22	IC50	0.6	nM	CHEMBL_ACT_6219441
REN	9.19	IC50	0.65	nM	CHEMBL_ACT_10866092
REN	9.19	IC50	0.65	nM	CHEMBL_ACT_3076310
REN	9.15	IC50	0.7	nM	CHEMBL_ACT_24828150
REN	9.15	IC50	0.7	nM	CHEMBL_ACT_24860365
REN	9.08	IC50	0.84	nM	CHEMBL_ACT_18292502
Q6DLW5	8.92	IC50	1.2	nM	CHEMBL_ACT_18292585
REN	8.66	IC50	2.21	nM	CHEMBL_ACT_6302123
REN	8.64	IC50	2.3	nM	CHEMBL_ACT_15767087
REN	8.6	IC50	2.5	nM	CHEMBL_ACT_24828148
REN	8.6	IC50	2.5	nM	CHEMBL_ACT_24860381
REN	8.52	IC50	3	nM	CHEMBL_ACT_18255663
P06281	8.35	IC50	4.5	nM	CHEMBL_ACT_3550881
P08424	7.1	IC50	80	nM	CHEMBL_ACT_3550880
P08424	7.06	IC50	88	nM	CHEMBL_ACT_18292583

Target pathways

Aggregated over 1 target gene(s): REN.

Top Reactome pathways

1 total, by targets touching each:

Pathway	Targets	Genes
Metabolism of Angiotensinogen to Angiotensins	1	REN

Dominant GO biological processes

GO term	Targets
kidney development	1
mesonephros development	1
angiotensin maturation	1
renin-angiotensin regulation of aldosterone production	1
proteolysis	1
regulation of blood pressure	1
male gonad development	1
hormone-mediated signaling pathway	1
response to lipopolysaccharide	1
response to immobilization stress	1
drinking behavior	1
regulation of MAPK cascade	1
cell maturation	1
amyloid-beta metabolic process	1
response to cAMP	1

Indications & clinical

Indications

18 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
cardiovascular disorder	4	MONDO:0004995	EFO:0000319
hypertensive disorder	3	MONDO:0005044	EFO:0000537
IgA glomerulonephritis	3	MONDO:0005342	EFO:0004194
congestive heart failure	3	MONDO:0005009	EFO:0000373
heart failure	3	MONDO:0005252	EFO:0003144
myocardial infarction	3	MONDO:0005068	EFO:0000612
atrial fibrillation	3	MONDO:0004981	EFO:0000275
diabetes mellitus	3	MONDO:0005015	EFO:0000400
coronary artery disorder	3	MONDO:0005010	MONDO:0021661
essential hypertension	3	MONDO:0001134	MONDO:0001134
Marfan syndrome	3	MONDO:0007947	MONDO:0007947
kidney disorder	2	MONDO:0005240	EFO:0003086
atherosclerosis	2	MONDO:0005311	EFO:0003914
diabetic kidney disease	2	MONDO:0005016	EFO:0000401
acute coronary syndrome	2	MONDO:0005542	EFO:0005672
chronic kidney disease	1	MONDO:0005300	EFO:0003884
type 2 diabetes mellitus	1	MONDO:0005148	MONDO:0005148

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 146.

Phase distribution

Phase	Trials
PHASE4	53
PHASE3	53
PHASE2	15
Not specified	11
PHASE1	9
PHASE1/PHASE2	4
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00441064	PHASE4	COMPLETED	Effect of High and Low Sodium Diets on Blood Pressure in Hypertensive Patients Treated With Aliskiren
NCT00542269	PHASE4	TERMINATED	Efficacy and Safety of Aliskiren/Ramipril/Amlodipine Compared With Ramipril/Amlodipine and Aliskiren/Amlodipine in Patients With Metabolic Syndrome
NCT00631917	PHASE4	COMPLETED	A Study Evaluating the Gastrointestinal (GI) Safety and Tolerability of Aliskiren Compared to Ramipril in Essential Hypertension
NCT00654875	PHASE4	COMPLETED	Efficacy and Safety of Once Daily Dosing of Aliskiren (300 mg (qd) Once a Day) to Twice Daily Dosing of Aliskiren (150 mg (Bid) Twice a Day) in Treating Moderate Hypertension.
NCT00660309	PHASE4	COMPLETED	A Clinical Study to Evaluate Renal Hemodynamic Responses to Aliskiren in Patients With Type 2 Diabetes Mellitus
NCT00719316	PHASE4	UNKNOWN	Aliskiren and Muscle Sympathetic Nerve Activity
NCT00760266	PHASE4	COMPLETED	Blood Pressure Lowering of Aliskiren HCTZ Compared to HCTZ in Stage 2 Systolic Hypertension in Older Population
NCT00765947	PHASE4	COMPLETED	Efficacy and Tolerability of an Aliskiren-based Treatment Algorithm in Patients With Mild to Moderate Hypertension
NCT00772577	PHASE4	COMPLETED	Study of the Efficacy and Safety of Aliskiren HCTZ vs Ramipril in Obese Patients (BMI ≥ 30) With Stage 2 Hypertension
NCT00787605	PHASE4	COMPLETED	Aliskiren HCTZ Compared to Amlodipine in Patients With Stage 2 Systolic Hypertension and Diabetes Mellitus
NCT00797316	PHASE4	COMPLETED	Aliskiren Plus HCTZ Compared to Aliskiren in Metabolic Syndrome Patients With Stage 2 Systolic Hypertension
NCT00809926	PHASE4	COMPLETED	8 Weeks Study to Evaluate the Efficacy and Safety of Valsartan in Combination With Aliskiren Compared to Valsartan Alone in Patients With Stage 2 Hypertension
NCT00818779	PHASE4	COMPLETED	Direct Renin Inhibition Effects on Atherosclerotic Biomarkers
NCT00853957	PHASE4	COMPLETED	Efficacy and Safety of Aliskiren Administered in Combination With Amlodipine Versus Amlodipine Alone in African American Patients With Stage 2 Hypertension
NCT00865020	PHASE4	COMPLETED	Efficacy and Safety of Aliskiren 300 mg Compared to Telmisartan 80 mg After 1 Week of Treatment Withdrawal
NCT00922311	PHASE4	COMPLETED	Aliskiren for Proteinuric IgAN Despite Angiotensin Blockade
NCT00927394	PHASE4	COMPLETED	Aliskiren and Valsartan vs Valsartan Alone in Patients With Stage II Systolic Hypertension and Type II Diabetes Mellitus
NCT00942994	PHASE4	COMPLETED	Aliskiren/Amlodipine/Hydrochlorothiazide (HCTZ) Versus Aliskiren/Amlodipine in US Minority Patients With Stage II Systolic Hypertension
NCT00949351	PHASE4	UNKNOWN	Safety of Add on Aliskiren to Angiotensin Converting Enzyme Inhibitor (ACEI) and Angiotensin I Receptor Blocker (ARB) Treatment in Type 2 Diabetes With Nephropathy
NCT00961207	PHASE4	TERMINATED	Triple Blockade of the Renin Angiotensin Aldosterone System in Diabetic (Type 1&2) Proteinuric Patients
NCT00974922	PHASE4	TERMINATED	Vitamin D Deficiency in Patients With Hypertension
NCT00982033	PHASE4	COMPLETED	Effects of Aliskiren on Patient With Heart Failure and a Normal Ejection Fraction
NCT00994253	PHASE4	WITHDRAWN	Evaluating the Effect of Aliskiren Versus HCTZ on Coronary Flow Reserve in Hypertensive Type II Diabetics
NCT01040494	PHASE4	UNKNOWN	Add-on Aliskiren Treatment in Patients With Chronic Congestive Heart Failure
NCT01042392	PHASE4	COMPLETED	Efficacy of Aliskiren Compared to Ramipril in the Treatment of Moderate Systolic Hypertensive Patients
NCT01048047	PHASE4	UNKNOWN	Effects of Aliskiren/Amlodipine Versus Amlodipine Monotherapy on Ankle-foot Volume in Hypertensive Patients
NCT01056731	PHASE4	COMPLETED	A Clinical Study With Aliskiren Alone or in Combination Therapy With Diuretic Hctz in Venezuelan Hypertensive Patients.
NCT01060865	PHASE4	TERMINATED	Evaluation of Aliskiren Efficacy by Different Methods of Blood Pressure Measurements
NCT01070030	PHASE4	COMPLETED	Efficacy and Safety of Combination Therapy of Aliskiren/Amlodipine or Aliskiren/Amlodipine/Hydrochlorothiazide in Patients With Stage II Hypertension
NCT01095822	PHASE4	UNKNOWN	Effects of Valsartan and Aliskiren on Hemostatic Indices in Hypertensive Diabetics
NCT01129557	PHASE4	TERMINATED	Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
NCT01138423	PHASE4	COMPLETED	Treatment of Adiposity Related hypErTension (TARGET)
NCT01150201	PHASE4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01156207	PHASE4	UNKNOWN	Significance of Regional Ventriculo-arterial Coupling in Patients With Chronic Heart Failure
NCT01176032	PHASE4	COMPLETED	ALiskiren or Losartan Effects on bioMARKers of Myocardial Remodeling
NCT01184599	PHASE4	UNKNOWN	A Prospective Study of the Kidney Protective Effect of Aliskiren in Hypertensive Patients With IgA Nephropathy
NCT01219413	PHASE4	COMPLETED	Influence of Aliskiren on Proteinuria
NCT01235910	PHASE4	TERMINATED	Clinical Pharmacology of Aliskiren in Combination With Cyclosporine in Cardiac Transplantation
NCT01284114	PHASE4	COMPLETED	Effects of Aliskiren in Elderly Hypertensive Chronic Kidney Disease (CKD) Patients
NCT01305850	PHASE4	UNKNOWN	The Effect of Aliskiren and Losartan on Peritoneal Membrane in Continuous Ambulatory Peritoneal Dialysis Patients

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

9 molecules share ≥1 primary target. Top 9 by shared-target count:

Molecule	Source	Status	Shared targets
CAPTOPRIL	ChEMBL	Phase 4 (approved)	REN
SITOKIREN	ChEMBL	Phase 3	REN
DITEKIREN	ChEMBL	Phase 2	REN
ENALKIREN	ChEMBL	Phase 2	REN
IMARIKIREN	ChEMBL	Phase 2	REN
PEPSTATIN	ChEMBL	Phase 2	REN
REMIKIREN	ChEMBL	Phase 2	REN
TERLAKIREN	ChEMBL	Phase 2	REN
ZANKIREN	ChEMBL	Phase 2	REN