BMS201038: an anticholesteremic agent and microsomal triglycide transfer protein inhibitor [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
lomitapide : 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. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]
| ID Source | ID |
|---|---|
| PubMed CID | 9853053 |
| CHEMBL ID | 354541 |
| CHEBI ID | 72297 |
| SCHEMBL ID | 304604 |
| MeSH ID | M0449162 |
| Synonym |
|---|
| 9-(4-{4-[(4''''-trifluoromethyl-biphenyl-2-carbonyl)-amino]-piperidin-1-yl}-butyl)-9h-fluorene-9-carboxylic acid (2,2,2-trifluoro-ethyl)-amide |
| 9-(4-{4-[(4''-trifluoromethyl-biphenyl-2-carbonyl)-amino]-piperidin-1-yl}-butyl)-9h-fluorene-9-carboxylic acid (2,2,2-trifluoro-ethyl)-amide |
| bdbm50098320 |
| bms-201038-01 |
| bms-201038 |
| chebi:72297 , |
| lomitapide |
| CHEMBL354541 , |
| aegr-733 |
| 182431-12-5 |
| lomitapide (usan/inn) |
| D09637 |
| juxtapid |
| aegr-773 |
| lomitapida |
| aegr773 |
| lomitapidum |
| aegr 773 |
| n-(2,2,2-trifluoroethyl)-9-{4-[4-({[4'-(trifluoromethyl)biphenyl-2-yl]carbonyl}amino)piperidin-1-yl]butyl}-9h-fluorene-9-carboxamide |
| 9h-fluorene-9-carboxamide, n-(2,2,2-trifluoroethyl)-9-(4-(4-(((4'-(trifluoromethyl)(1,1'-biphenyl)-2-yl)carbonyl)amino)-1-piperidinyl)butyl)- |
| lojuxta |
| bms 201038-01 |
| 82kub0583f , |
| hsdb 8218 |
| bms201038 |
| bms 201038 |
| n-(2,2,2-trifluoroethyl)-9-{4-(4-({(4'-(trifluoromethyl)biphenyl-2- yl)carbonyl}amino)piperidin-1-yl)butyl}-9h-fluorene-9-carboxamide |
| aegr733 |
| lomitapide [usan:inn] |
| unii-82kub0583f |
| bms 201238 |
| aegr 733 |
| lomitapide [vandf] |
| lomitapide [who-dd] |
| lomitapide [mi] |
| lomitapide [usan] |
| lomitapide [inn] |
| n-(2,2,2-trifluoroethyl)-9-(4-(4-(((4'-(trifluoromethyl)biphenyl-2-yl)carbonyl)amino)piperidin-1-yl)butyl)-9h-fluorene-9-carboxamide |
| S11708 |
| S7635 |
| gtpl7439 |
| n-(2,2,2-trifluoroethyl)-9-[4-[4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]piperidin-1-yl]butyl]fluorene-9-carboxamide |
| DB08827 |
| SCHEMBL304604 |
| CS-3423 |
| AKOS025149590 |
| HY-14667 |
| AC-32635 |
| DTXSID50171294 , |
| J-690250 |
| n-(2,2,2-trifluoroethyl)-9-[4-(4-{2-[4-(trifluoromethyl)phenyl]benzamido}piperidin-1-yl)butyl]-9h-fluorene-9-carboxamide |
| HMS3653B17 |
| lomitapide, >=98% (hplc) |
| NCGC00386364-05 |
| SW220160-1 |
| aegr-733(lomitapide) |
| FT-0750236 |
| BCP06821 |
| AS-75234 |
| n-(2,2,2-trifluoroethyl)-9-(4-{4-[4'-(trifluoromethyl)-[1,1'-biphenyl]-2-amido]piperidin-1-yl}butyl)-9h-fluorene-9-carboxamide |
| aegr-733;bms-201038 |
| mfcd16620494 |
| n-(2,2,2-trifluoroethyl)-9-(4-(4-(4'-(trifluoromethyl)biphenyl-2-ylcarboxamido)piperidin-1-yl)butyl)-9h-fluorene-9-carboxamide |
| n-(2,2,2-trifluoroethyl)-9-(4-(4-(4'-(trifluoromethyl)-[1,1'-biphenyl]-2-ylcarboxamido)piperidin-1-yl)butyl)-9h-fluorene-9-carboxamide |
| n-(2,2,2-trifluoroethyl)-9-[4-[4-[4'-(trifluoromethyl)-[1,1'-biphenyl]-2-ylcarboxamido]piperidin-1-yl]butyl]-9h-fluorene-9-carboxamide |
| L0298 |
| Q1268941 |
| SB16780 |
| lomitapide free base |
| 182431-12-5 (free base) |
| n-(2,2,2-trifluoroethyl)-9-(4-(4-(4'-(trifluoromethyl)-[1,1'-biphenyl]-2-carboxamido)piperidin-1-yl)butyl)-9h-fluorene-9-carboxamide |
| AMY38746 |
| HMS3743K11 |
| CCG-270380 |
| NCGC00386364-01 |
| 9h-fluorene-9-carboxamide, n-(2,2,2-trifluoroethyl)-9-[4-[4-[[[4'-(trifluoromethyl)[1,1'-biphenyl]-2-yl]carbonyl]amino]-1-piperidinyl]butyl]- |
| dtxcid3093785 |
| n-(2,2,2-trifluoroethyl)-9-(4-(4-(((4'-(trifluoromethyl)biphenyl-2-\\\\r\\\\n yl)carbonyl)amino)piperidin-1-yl)butyl)-9h-fluorene-9-carboxamide |
| c10ax12 |
| SY234920 |
| Z1696860003 |
| Excerpt | Reference | Relevance |
|---|---|---|
| "The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs." | ( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019) | 0.51 |
| Excerpt | Relevance | Reference |
|---|---|---|
| " Another group of Zucker fatty rats was dosed orally with BMS-201038 (0." | ( Inhibition of microsomal triglyceride transfer protein improves insulin sensitivity and reduces atherogenic risk in Zucker fatty rats. Dhanesha, N; Dhote, V; Jain, M; Joharapurkar, A; Kshirsagar, S; Patel, A; Patel, V; Raval, S, 2011) | 0.37 |
| " In this study, the initial dosage of lomitapide was 5 mg once daily for two weeks, with upward titration thereafter to 10, 20, 40, and 60 mg at weeks 2, 6, 10, and 14, respectively, or until an individually assessed maximum dosage was achieved." | ( Lomitapide: a review of its use in adults with homozygous familial hypercholesterolemia. Perry, CM, 2013) | 0.39 |
| " Study treatments were administered orally for 3 days in five separate periods in which subjects were dosed with (1) a single dose of 75 mg lomitapide on Day 1 followed by a single dose of 200 mg on Day 3; (2) ketoconazole 200 mg BID; (3) ketoconazole with a single dose of 75 mg lomitapide on Day 3; (4) a single dose of 400 mg moxifloxacin on Day 3 and (5) placebo." | ( Lomitapide at supratherapeutic plasma levels does not prolong the Qtc interval--results from a TQT study with moxifloxacin and ketoconazole. Darpo, B; Ferber, G; Sager, P; Sumeray, M; Zhou, M, 2013) | 0.39 |
| "A full pharmacokinetic profile was performed for the probe drug on day 1 and day 8 (after 7 days of dosing with lomitapide [i." | ( Pharmacokinetic interactions of the microsomal triglyceride transfer protein inhibitor, lomitapide, with drugs commonly used in the management of hypercholesterolemia. Bloedon, LT; Cuchel, M; Duffy, D; Dunbar, RL; Gadi, R; Movva, R; Tuteja, S, 2014) | 0.4 |
| " The recommended initial dosage of lomitapide is 5 mg once daily, with subsequent upward dose adjustment at specified intervals according to tolerability." | ( Lomitapide: A novel agent for the treatment of homozygous familial hypercholesterolemia. Davis, KA; Miyares, MA, 2014) | 0.4 |
| "25 mg once daily, n = 32) dosing was initiated on days 11 or 8, respectively, with evening (arm 1) or morning (arm 2) dosing; at steady state (days 15 or 22), a single lomitapide dose was administered; CYP3A inhibitor dosing continued for 6 days." | ( Evaluation of the effects of the weak CYP3A inhibitors atorvastatin and ethinyl estradiol/norgestimate on lomitapide pharmacokinetics in healthy subjects. Dutta, S; Foulds, P; King, A; Korb, S; Patel, G; Sumeray, M; Wade, JR, 2016) | 0.43 |
| " After a median 19 months (interquartile range 11-41 months) of treatment with a mean dosage of 20 mg of lomitapide." | ( Efficacy and safety of lomitapide in homozygous familial hypercholesterolaemia: the pan-European retrospective observational study. Arca, M; Bini, S; Boersma, E; Cefalù, AB; D'Erasmo, L; Di Costanzo, A; Steward, K; van Lennep, JR, 2022) | 0.72 |
| Role | Description |
|---|---|
| anticholesteremic drug | A substance used to lower plasma cholesterol levels. |
| MTP inhibitor | An inhibitor that interferes with the action of MTP. |
| [role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Class | Description |
|---|---|
| piperidines | |
| fluorenes | An ortho-fused polycyclic arene in which the skeleton is composed of two benzene rings ortho-fused to cyclopentane. |
| benzamides | |
| (trifluoromethyl)benzenes | An organofluorine compound that is (trifluoromethyl)benzene and derivatives arising from substitution of one or more of the phenyl hydrogens. |
| [compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Protein | Taxonomy | Measurement | Average (µ) | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| cytochrome P450 family 3 subfamily A polypeptide 4 | Homo sapiens (human) | Potency | 1.8999 | 0.0123 | 7.9835 | 43.2770 | AID1645841 |
| G | Vesicular stomatitis virus | Potency | 15.0916 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| cytochrome P450 2D6 | Homo sapiens (human) | Potency | 1.0684 | 0.0010 | 8.3798 | 61.1304 | AID1645840 |
| Interferon beta | Homo sapiens (human) | Potency | 15.0916 | 0.0033 | 9.1582 | 39.8107 | AID1645842 |
| HLA class I histocompatibility antigen, B alpha chain | Homo sapiens (human) | Potency | 15.0916 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| Spike glycoprotein | Severe acute respiratory syndrome-related coronavirus | Potency | 39.8107 | 0.0096 | 10.5250 | 35.4813 | AID1479145 |
| Inositol hexakisphosphate kinase 1 | Homo sapiens (human) | Potency | 15.0916 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| cytochrome P450 2C9, partial | Homo sapiens (human) | Potency | 15.0916 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Delta-type opioid receptor | Mus musculus (house mouse) | IC50 (µMol) | 0.0008 | 0.0001 | 0.7298 | 10.0000 | AID105916 |
| Microsomal triglyceride transfer protein large subunit | Homo sapiens (human) | IC50 (µMol) | 0.0056 | 0.0000 | 0.7263 | 5.7500 | AID105916; AID105917; AID248670 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID54742 | Dose required for 50% lowering of plasma TC in standard-diet-fed cynomolgus monkeys | 2001 | Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6 | A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors. |
| AID54888 | PlasmaTC lowering was determined in standard-diet-fed cynomolgus monkeys after 16h of postdosing at 10 mg/kg | 2001 | Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6 | A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors. |
| AID54890 | PlasmaTC lowering was determined in standard-diet-fed cynomolgus monkeys after 16h of postdosing at 5 mg/kg | 2001 | Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6 | A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors. |
| AID248670 | In vitro inhibitory concentration against human Microsomal triglyceride transfer protein | 2004 | Bioorganic & medicinal chemistry letters, Oct-18, Volume: 14, Issue:20 | 5-Carboxamido-1,3,2-dioxaphosphorinanes, potent inhibitors of MTP. |
| AID54887 | PlasmaTC lowering was determined in standard-diet-fed cynomolgus monkeys after 16h of postdosing at 1.25 mg/kg | 2001 | Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6 | A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors. |
| AID54889 | PlasmaTC lowering was determined in standard-diet-fed cynomolgus monkeys after 16h of postdosing at 2.5 mg/kg | 2001 | Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6 | A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors. |
| AID246903 | Concentration required for change in serum HDL cholesterol in male hamster after 3-day treatment | 2004 | Bioorganic & medicinal chemistry letters, Oct-18, Volume: 14, Issue:20 | 5-Carboxamido-1,3,2-dioxaphosphorinanes, potent inhibitors of MTP. |
| AID105917 | In vitro inhibition of human microsomal triglyceride transfer protein using triglyceride transfer assay | 2001 | Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6 | A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors. |
| AID221938 | Dose required for 50% lowering of plasma TC in standard-diet-fed golden Syrian hamsters 16h postdosing | 2001 | Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6 | A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors. |
| AID250106 | Percentage change in serum HDL cholesterol in male hamster after 3-day treatment at 30 mpk | 2004 | Bioorganic & medicinal chemistry letters, Oct-18, Volume: 14, Issue:20 | 5-Carboxamido-1,3,2-dioxaphosphorinanes, potent inhibitors of MTP. |
| AID246906 | inhibitory activity against secretion of lipoproteins apoB and apoA1 from human HepG2 cell lines | 2004 | Bioorganic & medicinal chemistry letters, Oct-18, Volume: 14, Issue:20 | 5-Carboxamido-1,3,2-dioxaphosphorinanes, potent inhibitors of MTP. |
| AID105916 | In vitro inhibition of human microsomal triglyceride transfer protein in HepG2 cells using apoB secretion assay | 2001 | Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6 | A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors. |
| AID1296008 | Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening | 2020 | SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1 | Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening. |
| AID1346987 | P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| AID1347160 | Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors | 2020 | Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49 | Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. |
| AID1347159 | Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay | 2020 | Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49 | Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. |
| AID1346986 | P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 7 (6.14) | 29.6817 |
| 2010's | 83 (72.81) | 24.3611 |
| 2020's | 24 (21.05) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.
| This Compound (10.87) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 13 (10.16%) | 5.53% |
| Reviews | 52 (40.63%) | 6.00% |
| Case Studies | 15 (11.72%) | 4.05% |
| Observational | 3 (2.34%) | 0.25% |
| Other | 45 (35.16%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||