Lomitapide

Summary

Lomitapide (CHEMBL354541) is an approved small-molecule anticholesteremic drug (ATC C10AX12); indicated across 3 conditions including cardiovascular disorder and familial hypercholesterolemia.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C10AX12
• Indications: 3 conditions
• Clinical trials: 17
• Chemistry: 693.7 Da · C39H37F6N3O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL354541
Name	Lomitapide
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	9853053
ChEBI	CHEBI:72297
ATC	C10AX12
Molecular formula	C39H37F6N3O2
Molecular weight	693.7
InChIKey	MBBCVAKAJPKAKM-UHFFFAOYSA-N

SMILES: C1CN(CCC1NC(=O)C2=CC=CC=C2C3=CC=C(C=C3)C(F)(F)F)CCCCC4(C5=CC=CC=C5C6=CC=CC=C64)C(=O)NCC(F)(F)F

IUPAC name: N-(2,2,2-trifluoroethyl)-9-[4-[4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]piperidin-1-yl]butyl]fluorene-9-carboxamide

ChEBI definition: A member of the class of benzamides obtained by formal condensation of the carboxy group of 4’-(trifluoromethyl)biphenyl-2-carboxylic acid with the primary amino group of 9-[4-(4-aminopiperidin-1-yl)butyl]-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide. Used (as its mesylate salt) as a complement to a low-fat diet and other lipid-lowering treatments in patients with homozygous familial hypercholesterolemia.

Pharmacological roles (ChEBI): anticholesteremic drug, MTP inhibitor.

Also known as: AEGR-733, Lojuxta, Lomitapida, Lomitapide, LOMITAPIDE, lomitapide

Parent form; salt/anhydrous children: CHEMBL2105662

Patent coverage: 459 distinct patent families (1,163 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

Broader ChEMBL bioactivity targets: 15 (assay-derived). Sample: Alpha-2A adrenergic receptor, D(1A) dopamine receptor, Thromboxane A2 receptor, Muscarinic acetylcholine receptor M2, Methionine synthase, Muscarinic acetylcholine receptor M1, Prostaglandin G/H synthase 1, Sodium-dependent noradrenaline transporter, Alpha-1A adrenergic receptor, Mu-type opioid receptor.

Bioactivity

ChEMBL activities: 14 potent at pChembl ≥ 5 of 17 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
MTR	9.3	IC50	0.5	nM	CHEMBL_ACT_25500443
MTTP	9.1	IC50	0.8	nM	CHEMBL_ACT_1223939
MTTP	8.1	IC50	8	nM	CHEMBL_ACT_1223938
MTTP	8.1	IC50	8	nM	CHEMBL_ACT_1454278
SLC6A3	6.62	AC50	239.1	nM	CHEMBL_ACT_25124902
KCNH2	6.07	AC50	860	nM	CHEMBL_ACT_25117523
DRD1	5.83	AC50	1492	nM	CHEMBL_ACT_25115153
DRD3	5.75	AC50	1758	nM	CHEMBL_ACT_25194467
SLC6A2	5.66	AC50	2204	nM	CHEMBL_ACT_25145943
ADRA1A	5.62	AC50	2404	nM	CHEMBL_ACT_25218802
CHRM1	5.41	AC50	3856	nM	CHEMBL_ACT_25210165
OPRM1	5.4	AC50	4022	nM	CHEMBL_ACT_25158118
ADORA3	5.36	AC50	4403	nM	CHEMBL_ACT_25198673
TBXA2R	5.07	AC50	8464	nM	CHEMBL_ACT_25211037

Target pathways

No target-pathway data for this drug (no mapped target genes).

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
cardiovascular disorder	3	MONDO:0004995	EFO:0000319
familial hypercholesterolemia	3	MONDO:0005439	EFO:0004911

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

Clinical trials

Total trials: 17.

Phase distribution

Phase	Trials
PHASE3	5
PHASE1	5
PHASE2	4
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00730236	PHASE3	COMPLETED	A Safety and Efficacy Study of AEGR-733 to Treat Homozygous Familial Hypercholesterolemia (FH)
NCT00943306	PHASE3	COMPLETED	Long Term, Follow-on Study of Lomitapide in Patients With Homozygous Familial Hypercholesterolemia
NCT02173158	PHASE3	COMPLETED	Efficacy and Safety of Lomitapide in Japanese Patients With HoFH on Concurrent Lipid-Lowering Therapy
NCT02765841	PHASE3	WITHDRAWN	Evaluate the Efficacy and Safety of Lomitapide in Pediatric Patients With Homozygous Familial Hypercholesterolemia on Stable Lipid-lowering Therapy
NCT04681170	PHASE3	COMPLETED	Efficacy and Safety of Lomitapide in Paediatric Patients With Homozygous Familial Hypercholesterolaemia (HoFH)
NCT00474240	PHASE2	COMPLETED	AEGR-733 and Atorvastatin 20 mg vs. Monotherapy in Moderate Hypercholesterolemia
NCT00559962	PHASE2	COMPLETED	Evaluate Low Doses of AEGR-733 on Hepatic Fat Accumulation by MRS
NCT00690443	PHASE2	COMPLETED	Evaluate Safety and Efficacy of AEGR-733 and Atorvastatin vs Atorvastatin Monotherapy in Hypercholesterolemia
NCT01556906	PHASE2	COMPLETED	Safety, Tolerability and Efficacy of Microsomal Triglyceride Protein (MTP) Inhibitor
NCT01760187	PHASE1	COMPLETED	Phase I Study of the Safety, Tolerability, PK & PD of Lomitapide in Japanese and Caucasian Subjects With Elevated LDL-C
NCT01915771	PHASE1	COMPLETED	Study to Determine the Intra-subject Variability of Pharmacokinetics of Lomitapide in Healthy Subjects
NCT02044419	PHASE1	COMPLETED	A Comparative Bioavailability Study of Lomitapide 20 mg Intact vs Sprinkled
NCT02080455	PHASE1	COMPLETED	Evaluate the Effect of Atorvastatin on the Pharmacokinetics of Lomitapide in Healthy Subjects.
NCT02080468	PHASE1	COMPLETED	Evaluate the Effect of Ethinyl Estradiol/Norgestimate on the Pharmacokinetics of Lomitapide in Healthy Female Subjects
NCT02135705	Not specified	COMPLETED	LOWER: Lomitapide Observational Worldwide Evaluation Registry
NCT02399839	Not specified	TERMINATED	Global Lomitapide Pregnancy Exposure Registry
NCT02399852	Not specified	WITHDRAWN	Effects of Lomitapide on Carotid and Aortic Atherosclerosis

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

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).