Evocalcet

Summary

Evocalcet (CHEMBL4297621) is a phase-3 clinical-stage small molecule (ATC H05BX06) targeting CASR; indicated across 3 conditions including secondary hyperparathyroidism and parathyroid gland disorder.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: H05BX06
• Targets: 1 (CASR)
• Indications: 3 conditions
• Clinical trials: 8
• Chemistry: 374.5 Da · C24H26N2O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4297621
Name	Evocalcet
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	71242808
ATC	H05BX06
Molecular formula	C24H26N2O2
Molecular weight	374.5
InChIKey	RZNUIYPHQFXBAN-XLIONFOSSA-N

SMILES: C[C@H](C1=CC=CC2=CC=CC=C21)N[C@H]3CCN(C3)C4=CC=C(C=C4)CC(=O)O

IUPAC name: 2-[4-[(3S)-3-[[(1R)-1-naphthalen-1-ylethyl]amino]pyrrolidin-1-yl]phenyl]acetic acid

Also known as: Evocalcet, KHK-7580, Khk7580, KHK7580, MT-4580, EVOCALCET

Parent form; salt/anhydrous children: CHEMBL4128835

Patent coverage: 23 distinct patent families (39 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 25 (64%) 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
CASR	CaS receptor	Positive	7.03	0.1%	P41180

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Extracellular calcium-sensing receptor.

Bioactivity

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

Target	pChembl	Type	Value	Unit	Activity ID
CASR	7.03	EC50	93	nM	CHEMBL_ACT_25570398

Target pathways

Aggregated over 1 target gene(s): CASR.

Top Reactome pathways

7 total, by targets touching each:

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

Dominant GO biological processes

GO term	Targets
ossification	1
response to ischemia	1
detection of calcium ion	1
intracellular calcium ion homeostasis	1
G protein-coupled receptor signaling pathway	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
JNK cascade	1
chemosensory behavior	1
positive regulation of cell population proliferation	1
anatomical structure morphogenesis	1
positive regulation of gene expression	1
positive regulation of insulin secretion	1
bile acid secretion	1
cellular response to hepatocyte growth factor stimulus	1

Indications & clinical

Indications

3 indications (0 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
secondary hyperparathyroidism	3	MONDO:0006964	EFO:1001173
parathyroid gland disorder	3	MONDO:0001223	EFO:0005754
hyperparathyroidism	1	MONDO:0001741	EFO:0008506

Clinical trials

Total trials: 8.

Phase distribution

Phase	Trials
PHASE3	4
PHASE1	2
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02549391	PHASE2/PHASE3	COMPLETED	Phase 3 Study of KHK7580
NCT02549404	PHASE3	COMPLETED	Phase 3 Study of KHK7580
NCT02549417	PHASE3	COMPLETED	Phase 3 Study of KHK7580
NCT03280264	PHASE3	COMPLETED	Phase 3 Study of KHK7580 for the Treatment of Hypercalcemia in Patients With Parathyroid Carcinoma or Primary Hyperparathyroidism
NCT03822507	PHASE3	COMPLETED	Study of KHK7580 in Subjects With Secondary Hyperparathyroidism in Asia
NCT01935856	PHASE1/PHASE2	COMPLETED	Phase 1/2 Study of KHK7580 for Secondary Hyperparathyroidism in Patients Receiving Hemodialysis
NCT02143271	PHASE1	COMPLETED	Study of KHK7580 for Secondary Hyperparathyroidism in Patients Receiving Peritoneal Dialysis
NCT04206657	PHASE1	COMPLETED	Pharmacokinetic Study of KHK7580 in Healthy Adult Volunteers

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

7 molecules share ≥1 primary target. Top 7 by shared-target count:

Molecule	Source	Status	Shared targets
CINACALCET	ChEMBL + PubChem	Phase 4 (approved)	CASR
ENCALERET	ChEMBL	Phase 3	CASR
FENDILINE	ChEMBL	Phase 2	CASR
RONACALERET	ChEMBL	Phase 2	CASR
SB-423562	ChEMBL	Phase 2	CASR
TECALCET	ChEMBL	Phase 2	CASR
tryptophan	PubChem	Approved	CASR