Lorundrostat

Summary

Lorundrostat (CHEMBL5095105) is a phase-3 clinical-stage small molecule targeting CYP11B1 and CYP11B2; indicated across 3 conditions including hypertensive disorder and heart failure.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (CYP11B1, CYP11B2)
• Indications: 3 conditions
• Clinical trials: 4
• Chemistry: 451.6 Da · C24H33N7O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL5095105
Name	Lorundrostat
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	126567187
Molecular formula	C24H33N7O2
Molecular weight	451.6
InChIKey	YHGVDZULVMINCJ-UHFFFAOYSA-N

SMILES: CC1=CC=C(C=C1)C2=CN=NC(=N2)N3CCN(CC3)CC(=O)NC4CCC(CC4)NC(=O)C

IUPAC name: N-(4-acetamidocyclohexyl)-2-[4-[5-(4-methylphenyl)-1,2,4-triazin-3-yl]piperazin-1-yl]acetamide

Also known as: Lorundrostat, MLS-101, MLS-101 FREE BASE, MLS101 FREE BASE, MT-4129, MT-4129 FREE BASE, MT4129 FREE BASE, LORUNDROSTAT, US10029993, Example 48

Parent form; salt/anhydrous children: CHEMBL6068393

Patent coverage: 17 distinct patent families (35 SureChEMBL compound mentions), from 2 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
CYP11B1	CYP11B1	Inhibition	6.32	0.1%	P15538
CYP11B2	CYP11B2	Inhibition	8.9	0.7%	P19099

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Cytochrome P450 11B2, mitochondrial.

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
CYP11B2	8.05	IC50	9	nM	CHEMBL_ACT_26901615

Target pathways

Aggregated over 2 target gene(s): CYP11B1, CYP11B2.

Top Reactome pathways

15 total, by targets touching each:

Pathway	Targets	Genes
Metabolism	2	CYP11B1, CYP11B2
Disease	2	CYP11B1, CYP11B2
Glucocorticoid biosynthesis	2	CYP11B1, CYP11B2
Metabolism of steroid hormones	2	CYP11B1, CYP11B2
Biological oxidations	2	CYP11B1, CYP11B2
Cytochrome P450 - arranged by substrate type	2	CYP11B1, CYP11B2
Phase I - Functionalization of compounds	2	CYP11B1, CYP11B2
Endogenous sterols	2	CYP11B1, CYP11B2
Metabolism of lipids	2	CYP11B1, CYP11B2
Metabolic disorders of biological oxidation enzymes	2	CYP11B1, CYP11B2
Diseases of metabolism	2	CYP11B1, CYP11B2
Metabolism of steroids	2	CYP11B1, CYP11B2
Mineralocorticoid biosynthesis	1	CYP11B2
Defective CYP11B2 causes CMO-1 deficiency	1	CYP11B2
Defective CYP11B1 causes AH4	1	CYP11B1

Dominant GO biological processes

GO term	Targets
C21-steroid hormone biosynthetic process	2
glucocorticoid biosynthetic process	2
cholesterol metabolic process	2
sterol metabolic process	2
aldosterone biosynthetic process	2
cellular response to hormone stimulus	2
cortisol metabolic process	2
cortisol biosynthetic process	2
cellular response to potassium ion	2
cellular response to peptide hormone stimulus	2
alcohol metabolic process	2
lipid metabolic process	2
steroid biosynthetic process	2
immune response	1
regulation of blood pressure	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
hypertensive disorder	1	MONDO:0005044	EFO:0000537
heart failure	1	MONDO:0005252	EFO:0003144
chronic kidney disease	1	MONDO:0005300	EFO:0003884

Clinical trials

Total trials: 4.

Phase distribution

Phase	Trials
PHASE2	2
PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05968430	PHASE3	ACTIVE_NOT_RECRUITING	Open-Label Extension (OLE) Study to Assess Safety, Efficacy, and Tolerability of Lorundrostat in Subjects With Hypertension
NCT06150924	PHASE2	COMPLETED	Efficacy and Safety of Lorundrostat in Addition to Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) in Subjects With Hypertension and Chronic Kidney Disease (CKD) With Albuminuria
NCT06785454	PHASE2	COMPLETED	A Study to Assess the Efficacy and Safety of Lorundrostat in Participants With Obstructive Sleep Apnea and Hypertension
NCT02953132	PHASE1	COMPLETED	A Clinical Study to See How the Study Drug MT-4129 is Taken up by the Body in Healthy 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.

13 molecules share ≥1 primary target. Top 13 by shared-target count:

Molecule	Source	Status	Shared targets
ABIRATERONE	ChEMBL + PubChem	Phase 4 (approved)	CYP11B1, CYP11B2
ETOMIDATE	ChEMBL	Phase 4 (approved)	CYP11B1, CYP11B2
FLUCONAZOLE	ChEMBL	Phase 4 (approved)	CYP11B1, CYP11B2
KETOCONAZOLE	ChEMBL	Phase 4 (approved)	CYP11B1, CYP11B2
LETROZOLE	ChEMBL	Phase 4 (approved)	CYP11B1, CYP11B2
METYRAPONE	ChEMBL	Phase 4 (approved)	CYP11B1, CYP11B2
OSILODROSTAT	ChEMBL	Phase 4 (approved)	CYP11B1, CYP11B2
POSACONAZOLE	ChEMBL	Phase 4 (approved)	CYP11B1, CYP11B2
BAXDROSTAT	ChEMBL	Phase 3	CYP11B1, CYP11B2
DEXFADROSTAT	ChEMBL	Phase 2	CYP11B1, CYP11B2
FADROZOLE	ChEMBL	Phase 2	CYP11B1, CYP11B2
AZALANSTAT	ChEMBL	Phase 2	CYP11B1
VOROZOLE	ChEMBL	Phase 2	CYP11B1