aliskiren Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
renin inhibitors 119 173334-57-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • aliskiren
  • rasilez
  • tekturna
  • aliskiren hemifumarate
  • aliskiren fumarate
  • SPP100
Renin is secreted by the kidney in response to decreases in blood volume and renal perfusion. Renin cleaves angiotensinogen to form the inactive decapeptide angiotensin I (Ang I). Ang I is converted to the active octapeptide angiotensin II (Ang II) by ACE and non-ACE pathways. Ang II is a powerful vasoconstrictor and leads to the release of catecholamines from the adrenal medulla and prejunctional nerve endings. It also promotes aldosterone secretion and sodium reabsorption. Together, these effects increase blood pressure. Ang II also inhibits renin release, thus providing a negative feedback to the system. This cycle, from renin through angiotensin to aldosterone and its associated negative feedback loop, is known as the renin-angiotensin-aldosterone system (RAAS). Aliskiren is a direct renin inhibitor, decreasing plasma renin activity (PRA) and inhibiting the conversion of angiotensinogen to Ang I. Whether aliskiren affects other RAAS components, e.g., ACE or non-ACE pathways, is not known.
  • Molecular weight: 551.77
  • Formula: C30H53N3O6
  • CLOGP: 3.51
  • LIPINSKI: 1
  • HAC: 9
  • HDO: 4
  • TPSA: 146.13
  • ALOGS: -5.42
  • ROTB: 19

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.15 g O

ADMET properties:

PropertyValueReference
MRTD (Maximum Recommended Therapeutic Daily Dose) 7.77 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Hosey CM, Chan R, Benet LZ
S (Water solubility) 350 mg/mL Hosey CM, Chan R, Benet LZ
EoM (Fraction excreted unchanged in urine) 25 % Hosey CM, Chan R, Benet LZ
BA (Bioavailability) 2.50 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

DateAgencyCompanyOrphan
March 5, 2007 FDA NOVARTIS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Neurologic neglect syndrome 211.66 18.26 44 8976 642 46676400
Carotid artery thrombosis 208.94 18.26 44 8976 686 46676356
Personality disorder 207.41 18.26 58 8962 3075 46673967
Blood pressure inadequately controlled 192.12 18.26 59 8961 4347 46672695
Adjustment disorder 180.44 18.26 44 8976 1355 46675687
Hemiplegia 169.61 18.26 60 8960 6878 46670164
Angioedema 158.05 18.26 97 8923 39245 46637797
Affect lability 157.47 18.26 59 8961 7961 46669081
Blood creatinine increased 144.73 18.26 119 8901 76284 46600758
Muscle spasticity 133.89 18.26 58 8962 11382 46665660
Cerebrovascular accident 129.12 18.26 126 8894 100913 46576129
Motor dysfunction 119.43 18.26 47 8973 7235 46669807
Sensory loss 118.32 18.26 46 8974 6856 46670186
Hyperkalaemia 113.12 18.26 87 8933 50622 46626420
Aphasia 111.03 18.26 69 8951 28498 46648544
Hemiparesis 102.95 18.26 58 8962 20011 46657031
Coordination abnormal 97.88 18.26 46 8974 10903 46666139
Blood pressure increased 92.59 18.26 118 8902 126548 46550494
Dysphagia 90.52 18.26 92 8928 77220 46599822
Eating disorder 87.98 18.26 47 8973 14607 46662435
Dysarthria 87.26 18.26 66 8954 37432 46639610
Conjoined twins 86.54 18.26 18 9002 263 46676779
Hypertension 74.83 18.26 135 8885 196221 46480821
Blood urea increased 66.55 18.26 48 8972 25304 46651738
Intestinal malrotation 66.15 18.26 15 9005 334 46676708
Diabetes mellitus inadequate control 64.54 18.26 37 8983 13177 46663865
Congenital bladder anomaly 63.28 18.26 13 9007 178 46676864
Muscular weakness 63.03 18.26 83 8937 91761 46585281
Urachal abnormality 63.02 18.26 13 9007 182 46676860
Persistent cloaca 61.87 18.26 13 9007 200 46676842
Concomitant disease progression 61.71 18.26 21 8999 2141 46674901
Hypertensive crisis 55.70 18.26 34 8986 13581 46663461
Renal failure 52.26 18.26 85 8935 113509 46563533
Renal impairment 50.68 18.26 67 8953 74305 46602737
Blood potassium increased 48.86 18.26 34 8986 16933 46660109
Hyponatraemia 48.21 18.26 77 8943 101255 46575787
Off label use 47.90 18.26 8 9012 379833 46297209
Glomerular filtration rate decreased 42.27 18.26 27 8993 11667 46665375
Limb malformation 37.30 18.26 10 9010 451 46676591
Impaired work ability 33.32 18.26 24 8996 12612 46664430
Confusional state 33.11 18.26 86 8934 159806 46517236
Anal prolapse 32.07 18.26 7 9013 130 46676912
Acute kidney injury 30.98 18.26 108 8912 235747 46441295
Multiple drug therapy 30.58 18.26 10 9010 901 46676141
Rheumatoid arthritis 28.23 18.26 6 9014 240209 46436833
Oedema peripheral 28.17 18.26 81 8939 159625 46517417
Cardiac failure 26.64 18.26 52 8968 79896 46597146
Renin increased 25.46 18.26 6 9014 159 46676883
Anxiety 25.34 18.26 85 8935 181872 46495170
Urine albumin/creatinine ratio increased 25.25 18.26 6 9014 165 46676877
Left ventricular hypertrophy 24.50 18.26 14 9006 4949 46672093
Angina pectoris 24.49 18.26 28 8992 26747 46650295
Pharyngeal oedema 22.16 18.26 20 9000 14451 46662591
Periorbital oedema 21.68 18.26 13 9007 5022 46672020
Toxicity to various agents 21.62 18.26 7 9013 211759 46465283
Abortion induced 21.53 18.26 17 9003 10243 46666799
Swollen tongue 20.92 18.26 27 8993 29205 46647837
Oedema mouth 20.64 18.26 10 9010 2531 46674511
Exercise tolerance decreased 20.19 18.26 12 9008 4565 46672477
Rectocele 19.13 18.26 7 9013 882 46676160
Blood pressure diastolic decreased 18.61 18.26 18 9002 14193 46662849
Glycosylated haemoglobin increased 18.59 18.26 16 9004 10860 46666182

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Concomitant disease progression 250.23 18.00 68 7537 2452 29942421
Blood creatinine increased 207.43 18.00 177 7428 91198 29853675
Hyperkalaemia 121.95 18.00 114 7491 65896 29878977
Blood pressure inadequately controlled 109.11 18.00 36 7569 2534 29942339
Cardiac failure 106.48 18.00 118 7487 83300 29861573
Blood pressure increased 80.31 18.00 95 7510 71833 29873040
Renal impairment 74.53 18.00 99 7506 84085 29860788
Urine albumin/creatinine ratio increased 71.87 18.00 14 7591 106 29944767
Glycosylated haemoglobin increased 69.30 18.00 38 7567 9453 29935420
Blood urea increased 69.28 18.00 60 7545 31321 29913552
Blood potassium increased 64.47 18.00 44 7561 16169 29928704
Angina pectoris 64.28 18.00 56 7549 29462 29915411
Chronic kidney disease 59.69 18.00 60 7545 37778 29907095
Angioedema 47.87 18.00 51 7554 34333 29910540
Renal failure 45.82 18.00 101 7504 128865 29816008
Oedema peripheral 43.51 18.00 88 7517 105744 29839129
Glomerular filtration rate decreased 40.86 18.00 29 7576 11333 29933540
Proteinuria 37.91 18.00 32 7573 16113 29928760
Blood pressure diastolic decreased 37.52 18.00 22 7583 6209 29938664
Renin increased 35.16 18.00 7 7598 60 29944813
Off label use 35.03 18.00 10 7595 249280 29695593
Creatinine urine increased 33.97 18.00 8 7597 159 29944714
Hypertensive crisis 33.96 18.00 23 7582 8334 29936539
Diabetic nephropathy 33.87 18.00 14 7591 1855 29943018
Bundle branch block left 32.99 18.00 19 7586 5185 29939688
Dyspnoea 30.91 18.00 166 7439 333129 29611744
Renal artery stenosis 27.43 18.00 12 7593 1827 29943046
Cardiac failure chronic 25.91 18.00 17 7588 5846 29939027
Hypotension 25.87 18.00 110 7495 200455 29744418
Cardiac failure acute 25.29 18.00 20 7585 9189 29935684
Toxicity to various agents 25.06 18.00 7 7598 177176 29767697
Orthopnoea 24.65 18.00 15 7590 4525 29940348
Sudden cardiac death 24.59 18.00 14 7591 3738 29941135
Acute pulmonary oedema 24.32 18.00 18 7587 7497 29937376
Acute kidney injury 23.72 18.00 134 7471 273708 29671165
Hypertension 23.56 18.00 76 7529 121278 29823595
Defect conduction intraventricular 23.18 18.00 6 7599 178 29944695
Oedema 22.92 18.00 40 7565 42953 29901920
Bradycardia 22.85 18.00 51 7554 65475 29879398
Post procedural haematoma 22.77 18.00 10 7595 1537 29943336
Diabetes mellitus 22.38 18.00 39 7566 41826 29903047
Disease progression 22.27 18.00 57 7548 79817 29865056
Syncope 21.05 18.00 58 7547 84845 29860028
Atrioventricular block 20.39 18.00 16 7589 7266 29937607
Blood pressure decreased 20.32 18.00 40 7565 47035 29897838
Neutropenia 20.29 18.00 4 7601 128536 29816337
Microalbuminuria 19.58 18.00 7 7598 626 29944247
Atrioventricular block first degree 19.26 18.00 14 7591 5674 29939199
Eyelid oedema 18.42 18.00 13 7592 5032 29939841
Periorbital oedema 18.09 18.00 11 7594 3315 29941558

Pharmacologic Action:

SourceCodeDescription
ATC C09XA02 CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
OTHER AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
Renin-inhibitors
ATC C09DX02 CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), COMBINATIONS
Angiotensin II receptor blockers (ARBs), other combinations
ATC C09XA52 CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
OTHER AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
Renin-inhibitors
ATC C09XA53 CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
OTHER AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
Renin-inhibitors
ATC C09XA54 CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
OTHER AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
Renin-inhibitors
FDA MoA N0000175899 Renin Inhibitors
FDA EPC N0000175900 Renin Inhibitor
CHEBI has role CHEBI:35674 antihypertensive

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Hypertensive disorder indication 38341003 DOID:10763
Anuria contraindication 2472002 DOID:2983
Hypercholesterolemia contraindication 13644009
Hyperkalemia contraindication 14140009
Secondary angle-closure glaucoma contraindication 21571006
Hypovolemia contraindication 28560003
Obstruction of bile duct contraindication 30144000
Dehydration contraindication 34095006
Hyperuricemia contraindication 35885006 DOID:1920
Angioedema contraindication 41291007 DOID:1558
Hypokalemia contraindication 43339004
Low blood pressure contraindication 45007003
Systemic lupus erythematosus contraindication 55464009 DOID:9074
Sympathectomy contraindication 57071006
Acute nephropathy contraindication 58574008
Hepatic failure contraindication 59927004
Hypercalcemia contraindication 66931009 DOID:12678
Hyperparathyroidism contraindication 66999008 DOID:13543
Hypochloremic alkalosis contraindication 70134007
Hepatic coma contraindication 72836002 DOID:12550
Diabetes mellitus contraindication 73211009 DOID:9351
Chronic idiopathic constipation contraindication 82934008
Hyponatremia contraindication 89627008
Gout contraindication 90560007 DOID:13189
Hypomagnesemia contraindication 190855004
Acute pancreatitis contraindication 197456007 DOID:2913
Impaired renal function disorder contraindication 197663003
Disease of liver contraindication 235856003 DOID:409
Neonatal hyperbilirubinemia contraindication 281610001
Pregnancy, function contraindication 289908002
Renal artery stenosis contraindication 302233006
Neutropenic disorder contraindication 303011007 DOID:1227
Azotemia contraindication 445009001
Severe Aortic Valve Stenosis contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 12.53 acidic
pKa2 9.2 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 37.5MG BASE TEKTURNULL NODEN PHARMA N210709 Nov. 14, 2017 DISCN CAPSULE, PELLET ORAL May 14, 2021 PEDIATRIC EXCLUSIVITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Renin Enzyme INHIBITOR IC50 9.22 WOMBAT-PK CHEMBL
Multidrug resistance protein 1 Transporter Km 5.68 WOMBAT-PK
Cytochrome P450 3A4 Enzyme Km 4.61 WOMBAT-PK
Renin Enzyme IC50 8.70 CHEMBL
Renin Enzyme IC50 7.96 CHEMBL
Renin Enzyme IC50 8.10 CHEMBL
Renin-1 Enzyme IC50 8.35 CHEMBL
Renin Enzyme IC50 7.10 CHEMBL
Protease Enzyme Ki 7.12 CHEMBL

External reference:

IDSource
502FWN4Q32 UNII
4025960 VUID
N0000179765 NUI
D03208 KEGG_DRUG
173334-58-2 SECONDARY_CAS_RN
C1120110 UMLSCUI
CHEBI:601027 CHEBI
C41 PDB_CHEM_ID
CHEMBL1639 ChEMBL_ID
CHEMBL3545059 ChEMBL_ID
CHEMBL1667 ChEMBL_ID
DB09026 DRUGBANK_ID
5493444 PUBCHEM_CID
7992 INN_ID
C446481 MESH_SUPPLEMENTAL_RECORD_UI
4812 IUPHAR_LIGAND_ID
325646 RXNORM
108166 MMSL
23512 MMSL
310257 MMSL
34310 MMSL
d06665 MMSL
011991 NDDF
011995 NDDF
425981005 SNOMEDCT_US
426725002 SNOMEDCT_US
427002003 SNOMEDCT_US
4025960 VANDF
4030489 VANDF

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ALISKIREN HUMAN PRESCRIPTION DRUG LABEL 1 49884-424 TABLET, FILM COATED 150 mg ORAL ANDA 29 sections
ALISKIREN HUMAN PRESCRIPTION DRUG LABEL 1 49884-425 TABLET, FILM COATED 300 mg ORAL ANDA 29 sections
Tekturna HUMAN PRESCRIPTION DRUG LABEL 1 50090-2985 TABLET, FILM COATED 300 mg ORAL NDA 29 sections
Tekturna HUMAN PRESCRIPTION DRUG LABEL 1 50090-2985 TABLET, FILM COATED 300 mg ORAL NDA 29 sections
Tekturna HUMAN PRESCRIPTION DRUG LABEL 1 54868-5772 TABLET, FILM COATED 150 mg ORAL NDA 29 sections
Tekturna HCT HUMAN PRESCRIPTION DRUG LABEL 2 54868-6041 TABLET, FILM COATED 150 mg ORAL NDA 28 sections
Tekturna HUMAN PRESCRIPTION DRUG LABEL 1 54868-6042 TABLET, FILM COATED 300 mg ORAL NDA 29 sections
Tekturna HCT HUMAN PRESCRIPTION DRUG LABEL 2 54868-6103 TABLET, FILM COATED 300 mg ORAL NDA 28 sections
Tekturna HCT HUMAN PRESCRIPTION DRUG LABEL 2 54868-6194 TABLET, FILM COATED 300 mg ORAL NDA 28 sections
Aliskiren HUMAN PRESCRIPTION DRUG LABEL 1 66993-141 TABLET, FILM COATED 150 mg ORAL NDA authorized generic 28 sections
Aliskiren HUMAN PRESCRIPTION DRUG LABEL 1 66993-142 TABLET, FILM COATED 300 mg ORAL NDA authorized generic 28 sections
Tekturna HCT HUMAN PRESCRIPTION DRUG LABEL 2 70839-112 TABLET, FILM COATED 150 mg ORAL NDA 29 sections
Tekturna HCT HUMAN PRESCRIPTION DRUG LABEL 2 70839-125 TABLET, FILM COATED 150 mg ORAL NDA 29 sections
Tekturna HUMAN PRESCRIPTION DRUG LABEL 1 70839-150 TABLET, FILM COATED 150 mg ORAL NDA 28 sections
Tekturna HUMAN PRESCRIPTION DRUG LABEL 1 70839-300 TABLET, FILM COATED 300 mg ORAL NDA 28 sections
Tekturna HCT HUMAN PRESCRIPTION DRUG LABEL 2 70839-312 TABLET, FILM COATED 300 mg ORAL NDA 29 sections
Tekturna HCT HUMAN PRESCRIPTION DRUG LABEL 2 70839-325 TABLET, FILM COATED 300 mg ORAL NDA 29 sections