Encaleret

Summary

Encaleret (CHEMBL1672973) is a phase-3 clinical-stage small molecule targeting CASR; indicated across 2 conditions including hypoparathyroidism.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (CASR)
• Indications: 2 conditions
• Clinical trials: 4
• Chemistry: 514 Da · C29H33ClFNO4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1672973
Name	Encaleret
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	46917559
Molecular formula	C29H33ClFNO4
Molecular weight	514
InChIKey	UNFHDRVFEQPUEL-DENIHFKCSA-N

SMILES: CC1=C(C=CC(=C1)C2=CC=CC=C2[C@@H](C)OC[C@@H](CNC(C)(C)CC3=CC(=C(C=C3)Cl)F)O)C(=O)O

IUPAC name: 4-[2-[(1R)-1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenyl]-2-methylbenzoic acid

Also known as: Encaleret, JTT-305, ENCALERET

Parent form; salt/anhydrous children: CHEMBL2105731

Patent coverage: 12 distinct patent families (33 SureChEMBL compound mentions), from 3 matched compound structure(s). 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	Negative	7.9	0.1%	P41180

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Extracellular calcium-sensing receptor, Beta-2 adrenergic receptor, Cytochrome P450 2D6.

Bioactivity

ChEMBL activities: 2 potent at pChembl ≥ 5 of 3 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CASR	7.92	IC50	12	nM	CHEMBL_ACT_5223165
ADRB2	5.77	IC50	1700	nM	CHEMBL_ACT_5223191

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

1 disease in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
hypoparathyroidism	2	MONDO:0001220	EFO:0009451

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

Clinical trials

Total trials: 4.

Phase distribution

Phase	Trials
PHASE2	2
PHASE3	1
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05680818	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Encaleret Compared to Standard of Care in Participants With ADH1
NCT07080385	PHASE2/PHASE3	RECRUITING	Pharmacokinetics, Efficacy, and Safety of Encaleret in Pediatric Participants With Autosomal Dominant Hypocalcemia Type 1 (ADH1)
NCT04581629	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of Encaleret in Participants With Autosomal Dominant Hypocalcemia (ADH) Type 1
NCT05735015	PHASE2	COMPLETED	PTH-independent Effects of Encaleret

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
EVOCALCET	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