Cinacalcet

Summary

Cinacalcet (CHEMBL1201284) is an approved small-molecule P450 inhibitor (ATC H05BX01) targeting GRM5 and CASR; indicated across 9 conditions including parathyroid gland disorder and secondary hyperparathyroidism.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: H05BX01
• Targets: 2 (GRM5, CASR)
• Indications: 9 conditions
• Clinical trials: 54
• Chemistry: 357.4 Da · C22H22F3N

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1201284
Name	Cinacalcet
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	156419
ChEBI	CHEBI:48390
ATC	H05BX01
Molecular formula	C22H22F3N
Molecular weight	357.4
InChIKey	VDHAWDNDOKGFTD-MRXNPFEDSA-N

SMILES: C[C@H](C1=CC=CC2=CC=CC=C21)NCCCC3=CC(=CC=C3)C(F)(F)F

IUPAC name: N-[(1R)-1-naphthalen-1-ylethyl]-3-[3-(trifluoromethyl)phenyl]propan-1-amine

ChEBI definition: A secondary amino compound that is (1R)-1-(naphthalen-1-yl)ethanamine in which one of the hydrogens attached to the nitrogen is substituted by a 3-[3-(trifluoromethyl)phenyl]propyl group.

Pharmacological roles (ChEBI): calcimimetic, P450 inhibitor.

Also known as: AMG 073, AMG-073, AMG073, Cinacalcet, KRN-1493, KRN1493, SID50125742, SID124893630, cinacalcet, CINACALCET, Cinacalcet hydrochlorideÊ, CINACALCET HYDROCHLORIDE

Parent form; salt/anhydrous children: CHEMBL1200776

Patent coverage: 1,530 distinct patent families (5,917 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 5,701 (96%) 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
GRM5	mGlu5 receptor	Positive	4.35	0.2%	P41594
CASR	CaS receptor	Positive	6.6	0.1%	P41180

Broader ChEMBL bioactivity targets: 27 (assay-derived). Sample: Nuclear receptor ROR-gamma, 4’-phosphopantetheinyl transferase ffp, Vasopressin V2 receptor, Extracellular calcium-sensing receptor, Alpha-2C adrenergic receptor, Beta-1 adrenergic receptor, Muscarinic acetylcholine receptor M1, D(2) dopamine receptor, Motilin receptor, Sodium-dependent noradrenaline transporter.

Bioactivity

ChEMBL activities: 20 potent at pChembl ≥ 5 of 33 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CASR	8.4	EC50	4	nM	CHEMBL_ACT_25570397
CYP2D6	7.3	IC50	50	nM	CHEMBL_ACT_17800254
CYP2D6	7.3	IC50	50	nM	CHEMBL_ACT_26645421
CASR	7.1	EC50	80	nM	CHEMBL_ACT_12719037
GLRA1	6.5	EC50	320	nM	CHEMBL_ACT_15241385
HTR2C	6.14	AC50	730	nM	CHEMBL_ACT_25131750
ADRA2C	6.08	AC50	830	nM	CHEMBL_ACT_25147818
KCNH2	5.89	AC50	1300	nM	CHEMBL_ACT_25117788
DRD3	5.82	AC50	1500	nM	CHEMBL_ACT_25193468
SLC6A4	5.75	AC50	1800	nM	CHEMBL_ACT_25150280
OPRM1	5.72	AC50	1900	nM	CHEMBL_ACT_25146892
OPRM1	5.6	AC50	2500	nM	CHEMBL_ACT_25157408
CASR	5.55	IC50	2800	nM	CHEMBL_ACT_29252824
DRD2	5.44	AC50	3600	nM	CHEMBL_ACT_25140273
P0DTD1	5.22	IC50	5990	nM	CHEMBL_ACT_25952252
SLC6A3	5.19	AC50	6400	nM	CHEMBL_ACT_25123894
SLC6A2	5.14	AC50	7200	nM	CHEMBL_ACT_25144944
ADORA3	5.09	AC50	8100	nM	CHEMBL_ACT_25134153
ADRB1	5.06	AC50	8800	nM	CHEMBL_ACT_25121720
GHSR	5	AC50	10000	nM	CHEMBL_ACT_25172699

Target pathways

Aggregated over 2 target gene(s): GRM5, CASR.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
G alpha (q) signalling events	2	CASR, GRM5
Class C/3 (Metabotropic glutamate/pheromone receptors)	2	CASR, GRM5
Signal Transduction	1	CASR
Signaling by GPCR	1	CASR
GPCR downstream signalling	1	CASR
G alpha (i) signalling events	1	CASR
GPCR ligand binding	1	CASR
Neurexins and neuroligins	1	GRM5

Dominant GO biological processes

GO term	Targets
signal transduction	2
G protein-coupled receptor signaling pathway	2
temperature homeostasis	1
response to amphetamine	1
desensitization of G protein-coupled receptor signaling pathway	1
regulation of DNA-templated transcription	1
positive regulation of cytosolic calcium ion concentration	1
phospholipase C-activating G protein-coupled glutamate receptor signaling pathway	1
G protein-coupled glutamate receptor signaling pathway	1
chemical synaptic transmission	1
learning or memory	1
locomotory behavior	1
positive regulation of dopamine secretion	1
operant conditioning	1
protein localization to nuclear inner membrane	1

Indications & clinical

Indications

9 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
parathyroid gland disorder	4	MONDO:0001223	EFO:0005754
secondary hyperparathyroidism	3	MONDO:0006964	EFO:1001173
chronic kidney disease	3	MONDO:0005300	EFO:0003884
hyperparathyroidism	3	MONDO:0001741	EFO:0008506
primary hyperparathyroidism	2	MONDO:0010837	EFO:0008519
renal osteodystrophy	2	MONDO:0006946	EFO:1001152
hypophosphatemic rickets	1	MONDO:0024300	MONDO:0024300

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

Clinical trials

Total trials: 54.

Phase distribution

Phase	Trials
PHASE4	17
PHASE2	13
PHASE3	11
Not specified	8
PHASE1	3
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03994172	PHASE4	ACTIVE_NOT_RECRUITING	Novel Combination Therapy for Osteoporosis in Men
NCT00110890	PHASE4	COMPLETED	A Research Study for Patients With End-Stage Renal Disease (ESRD)
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00431496	PHASE4	COMPLETED	A Study of Cinacalcet to Improve Achievement of National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) Targets in Patients With End Stage Renal Disease (ESRD)
NCT00446329	PHASE4	TERMINATED	Cinacalcet for Secondary Hyperparathyroidism in Patients Receiving Hemodialysis
NCT00803712	PHASE4	COMPLETED	20070360 Incident Dialysis
NCT00977080	PHASE4	COMPLETED	Evaluation of the Effectiveness of Paricalcitol Versus Cinacalcet With Low-Dose Vitamin D
NCT01100723	PHASE4	COMPLETED	Trial to Optimize Mineral Outcomes in Dialysis Patients
NCT01101113	PHASE4	COMPLETED	Cinacalcet stUdy for Peritoneal Dialysis Patients In Double Arm on the Lowing Effect OF iPTH Level
NCT01103206	PHASE4	COMPLETED	Evaluation of a Cincalcet Suppression Test
NCT01143987	PHASE4	COMPLETED	Cincalcet and Vascular Arterial Stiffness Among Peritoneal Dialysis Patients With Secondary Hyperparathyroidism
NCT01178450	PHASE4	COMPLETED	Parathyroidectomy vs Cinacalcet in the Treatment of Secondary Hyperparathyroidism Post Renal Transplantation
NCT01181531	PHASE4	COMPLETED	Compare the Efficacy of Cinacalcet vs Traditional Vitamin D for Secondary Hyperparathyroidism (SHPT) Among Subjects Undergoing Hemodialysis
NCT01250405	PHASE4	COMPLETED	Acute Effects of Cinacalcet on Arterial Stiffness and Ventricular Function in Hemodialysis Patients
NCT01447368	PHASE4	COMPLETED	Cinacalcet Versus Parathyroidectomy in Peritoneal Dialysis Patients
NCT02417389	PHASE4	COMPLETED	Efficacy of Cinacalcet in the Control of Primary Hyperparathyroidism
NCT05926570	PHASE4	COMPLETED	Parathyroid Hormone Level and Growth in Pediatric Patients With ESRD on Regular Hemodialysis
NCT07122401	PHASE3	RECRUITING	Study of MT1013 for the Treatment of Patients With Secondary Hyperparathyroidism
NCT00117052	PHASE3	COMPLETED	SENSOR: Study to Investigate Cinacalcet Treatment in Haemodialysis Patients With Secondary Hyperparathyroidism
NCT00345839	PHASE3	COMPLETED	E.V.O.L.V.E. Trial™: EValuation Of Cinacalcet Hydrochloride (HCl) Therapy to Lower CardioVascular Events
NCT00975000	PHASE3	COMPLETED	Treatment of Autonomous Hyperparathyroidism in Post Renal Transplant Recipients
NCT00975221	PHASE3	COMPLETED	Efficacy and Safety Study of Cinacalcet for the Treatment of Hypercalcemia in Patients With Primary Hyperparathyroidism Unable to Undergo Parathyroidectomy
NCT01011699	PHASE3	TERMINATED	Nicotinamide Versus Sevelamer Hydrochloride on Phosphatemia Control on Chronic Hemodialysed Patients
NCT01277510	PHASE3	TERMINATED	Pediatric Chronic Kidney Disease Safety and Efficacy
NCT01896232	PHASE3	COMPLETED	Head-to-Head Study of Etelcalcetide (AMG 416) and Cinacalcet
NCT02341417	PHASE3	COMPLETED	Extension Study of Cinacalcet for Treatment of Secondary Hyperparathyroidism (SHPT) in Pediatric Patients With Chronic Kidney Disease on Dialysis
NCT02525796	PHASE2/PHASE3	COMPLETED	Evaluating Alternative Medical Therapies in Primary Hyperparathyroidism
NCT02549391	PHASE2/PHASE3	COMPLETED	Phase 3 Study of KHK7580
NCT03299244	PHASE3	COMPLETED	Head-to-Head Study of Etelcalcetide and Cinacalcet in Asian Hemodialysis Patients With Secondary Hyperparathyroidism (SHPT)
NCT03822507	PHASE3	COMPLETED	Study of KHK7580 in Subjects With Secondary Hyperparathyroidism in Asia
NCT00113945	PHASE2	COMPLETED	Research Study Evaluating Cinacalcet for Patients With End Stage Renal Disease (ESRD)
NCT00113958	PHASE2	COMPLETED	Cinacalcet Study to Reach Kidney Disease Outcomes Quality Initiative (K/DOQI) Levels
NCT00656032	PHASE2	COMPLETED	Vitamin D, Insulin Resistance and Inflammation in ESRD
NCT00936650	PHASE2	COMPLETED	A Study to Assess the Efficacy and Safety of Twice-Daily Dose Regimens of an Oral Calcimimetic Agent AMG 073 (Cinacalcet) in Primary Hyperparathyroidism (PHPT)
NCT00936988	PHASE2	COMPLETED	A Multicenter, Open-label Extension Study to Assess the Long-term Safety and Efficacy of an Oral Calcimimetic Agent AMG 073 (Cinacalcet) in Primary Hyperparathyroidism
NCT01054079	PHASE2	COMPLETED	Cinacalcet Hydrochloride in Treating Men With Recurrent Prostate Cancer
NCT01439867	PHASE2	TERMINATED	Safety & Tolerability of Cinacalcet in Pediatric Patients With Chronic Kidney Disease and Secondary Hyperparathyroidism
NCT01599962	PHASE2	COMPLETED	Influence of Cincalcet on Cognitive Functions in Healthy Human Subjects
NCT02133404	PHASE2	COMPLETED	A Study to Evaluate the Effect of ASP7991 in Secondary Hyperparathyroidism Patients Undergoing Hemodialysis
NCT02216656	PHASE2	COMPLETED	Phase 2 Study of KHK7580

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 1 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

15 molecules share ≥1 primary target. Top 15 by shared-target count:

Molecule	Source	Status	Shared targets
ENCALERET	ChEMBL	Phase 3	CASR
EVOCALCET	ChEMBL	Phase 3	CASR
GLUTAMIC ACID	ChEMBL	Phase 3	GRM5
BASIMGLURANT	ChEMBL	Phase 2	GRM5
DIPRAGLURANT	ChEMBL	Phase 2	GRM5
FENDILINE	ChEMBL	Phase 2	CASR
FENOBAM	ChEMBL	Phase 2	GRM5
KAINIC ACID	ChEMBL	Phase 2	GRM5
MAVOGLURANT	ChEMBL	Phase 2	GRM5
QUINPIROLE	ChEMBL	Phase 2	GRM5
RASEGLURANT	ChEMBL	Phase 2	GRM5
RONACALERET	ChEMBL	Phase 2	CASR
SB-423562	ChEMBL	Phase 2	CASR
TECALCET	ChEMBL	Phase 2	CASR
tryptophan	PubChem	Approved	CASR