Skip to main content

2010 New Drug Approvals - Pt. XV - Lurasidone (Latuda)

By


ATC code (partial): N05AE


On October 28th 2010, the FDA approved Lurasidone (Tradename:Latuda) (Lurasidone is also known by the research code SM-13,496). Lurasidone is an atypical antipsychotic agent indicated for the treatment schizophrenia.

Lurasidone displays broad polypharmacology against a wide range of rhodopsin-like aminergic GPCRs, acting as an antagonist with high affinity at dopamine D2 receptors (Uniprot: P14416, ChEMBL: 72) (Ki of 1 nM), serotonin 5-HT2A (Uniprot: P28223, ChEMBL: 107) (Ki of 0.47 nM) and 5-HT7 receptors (Uniprot: P34969, ChEMBL: 10209) (Ki of 0.49 nM), and with moderate affinity at alpha-2C adrenergic receptors (Uniprot: P18825, ChEMBL: 218) (Ki of 10.8 nM) and at alpha-2A adrenergic receptors (Uniprot: P08913, ChEMBL: 52) (Ki of 40.7 nM). Lurasidone acts also as a partial agonist at serotonin 5-HT1A receptors (Uniprot: P08908, ChEMBL: 51) (Ki of 6.4 nM) and exhibits little or no affinity for histamine H1 (Uniprot: P35367, ChEMBL: 127) and muscarinic M1 receptors (Uniprot: P11229, ChEMBL: 61) (IC50 > 1000 nM and IC50 > 1000 nM, respectively). The efficacy of Luasidone is thought to be primarily related to the D2 and 5HT2A antagonism. All atypical antipsychotics display this complex polypharmacology.

Lurasidone is a synthetic small-molecule drug (Molecular Weight of 492.7 g/mol for Lurasidone itself and 529.14 g.mol-1 for the dosed HCl salt), is fully Rule-of-Five compliant, lipophilic and very slightly soluble in water.

Lurasidone has low systemic bioavailability (9-19%), and a high volume of distribution of 6173L, and displays high plasma protein binding (ppb) of ~99%. The half life is 18 hours, and steady-state plasma levels are reached 7 days after starting regular dosing. Lurasidone is predominantly metabolized by CYP3A4 into four major metabolites (two active metabolites and two 'inactive') - metabolites include hydroxylation of the nornbornane ring, N-dealkylation and S-oxidation. The apparent clearance is 3902mL/min, with the bulk of the drug being excreted in the feces. Dosage is oral, with a recommended starting dosage is 40 mg once daily (equivalent to 81umol), with a recommended maximum dosage of 80 mg daily.


Lurasidone is a chiral benzoisothiazol derivative - the benzoisothiazol is the fused five-six dual ring structure on the right of the figure above. Its structure (3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-ylmethyl] cyclohexylmethyl}hexahydro-4,7-methano-2H-isoindole-1,3-dione contains an imide heterocyclic and a piperazine functional group. The central piperazine nitrogen is basic. The chemical structure, properties and pharmacology are similar to Ziprasidone (Trademark:Geodon). 

NAME="Lurasidone"
TRADEMARK_NAME="Latuda"
ATC_code= NA
SMILES="O=C1C2[C@@H]3CC[C@@H](C3)C2C(=O)N1C[C@@H]4CCCC[C@H]4CN5CCN(CC5)c6nsc7ccccc67"
InChI="InChI=1S/C28H36N4O2S/c33-27-24-18-9-10-19(15-18)25(24)28(34)32(27)17-21-6-2-1-5-20(21)16-30-11-13-31(14-12-30)26-22-7-3-4-8-23(22)35-29-26/h3-4,7-8,18-21,24-25H,1-2,5-6,9-17H2/t18-,19+,20-,21-,24?,25?/m0/s1"
ChemDraw=Lurasidone.cdx

The full prescribing information can be found here.

Lurasidone has a boxed warning (colloquially known as a 'black box').

The license holder is Sunovion Pharmaceuticals Inc. and the product website is www.latuda.com
Labels:

Comments

Post a Comment

Popular posts from this blog

New SureChEMBL announcement

By
(Generated with DALL-E 3 ∙ 30 October 2023 at 1:48 pm) We have some very exciting news to report: the new SureChEMBL is now available! Hooray! What is SureChEMBL, you may ask. Good question! In our portfolio of chemical biology services, alongside our established database of bioactivity data for drug-like molecules ChEMBL , our dictionary of annotated small molecule entities ChEBI , and our compound cross-referencing system UniChem , we also deliver a database of annotated patents! Almost 10 years ago , EMBL-EBI acquired the SureChem system of chemically annotated patents and made this freely accessible in the public domain as SureChEMBL. Since then, our team has continued to maintain and deliver SureChEMBL. However, this has become increasingly challenging due to the complexities of the underlying codebase. We were awarded a Wellcome Trust grant in 2021 to completely overhaul SureChEMBL, with a new UI, backend infrastructure, and new f
Post a Comment
Read more

Legacy SureChEMBL retirement

By
Dear SureChEMBL users, About six months ago, we introduced the new version of SureChEMBL . It brought significant improvements in terms of performance and stability, and it also allows us to implement new functionalities. After the survey at the beginning of the year, we prioritised what should be delivered first. You should see the materialisation of our work in the coming months. As originally announced when the new SureChEMBL was introduced, the plan was to shut down the old system permanently to focus all our resources on the new SureChEMBL. This time has come, so expect www.surechembl-legacy.org to be unreachable in the coming days with no turning back! Consequently, and in parallel, the new SureChEMBL will lose its Beta status, and we will stop referring to it as the new version. This does not mean we are reducing our efforts to improve our system; on the contrary, this removes a distraction! If you have any feedback, you can contact us directly at surechembl-help@ebi.ac.uk . W
Post a Comment
Read more

ChEMBL & SureChEMBL anniversary symposium

By
  In 2024 we celebrate the 15th anniversary of the first public release of the ChEMBL database as well as the 10th anniversary of SureChEMBL. To recognise this important landmark we are organising a two-day symposium to celebrate the work achieved by ChEMBL and SureChEMBL, and look forward to its future.   Save the date for the ChEMBL 15 Year Symposium October 1-2, 2024     Day one will consist of four workshops, a basic ChEMBL drug design workshop; an advanced ChEMBL workshop (EUbOPEN community workshop); a ChEMBL data deposition workshop; and a SureChEMBL workshop. Day two will consist of a series of talks from invited speakers, a few poster flash talks, a local nature walk, as well as celebratory cake. During the breaks, the poster session will be a great opportunity to catch up with other users and collaborators of the ChEMBL resources and chat to colleagues, co-workers and others to find out more about how the database is being used. Lunch and refreshments will be pro
Post a Comment
Read more

ChEMBL 34 is out!

By
We are delighted to announce the release of ChEMBL 34, which includes a full update to drug and clinical candidate drug data. This version of the database, prepared on 28/03/2024 contains:         2,431,025 compounds (of which 2,409,270 have mol files)         3,106,257 compound records (non-unique compounds)         20,772,701 activities         1,644,390 assays         15,598 targets         89,892 documents Data can be downloaded from the ChEMBL FTP site:  https://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/releases/chembl_34/ Please see ChEMBL_34 release notes for full details of all changes in this release:  https://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/releases/chembl_34/chembl_34_release_notes.txt New Data Sources European Medicines Agency (src_id = 66): European Medicines Agency's data correspond to EMA drugs prior to 20 January 2023 (excluding vaccines). 71 out of the 882 newly added EMA drugs are only authorised by EMA, rather than from other regulatory bodies e.g.
Post a Comment
Read more

A python client for accessing ChEMBL web services

By
Motivation The CheMBL Web Services provide simple reliable programmatic access to the data stored in ChEMBL database. RESTful API approaches are quite easy to master in most languages but still require writing a few lines of code. Additionally, it can be a challenging task to write a nontrivial application using REST without any examples. These factors were the motivation for us to write a small client library for accessing web services from Python. Why Python? We choose this language because Python has become extremely popular (and still growing in use) in scientific applications; there are several Open Source chemical toolkits available in this language, and so the wealth of ChEMBL resources and functionality of those toolkits can be easily combined. Moreover, Python is a very web-friendly language and we wanted to show how easy complex resource acquisition can be expressed in Python. Reinventing the wheel? There are already some libraries providing access to ChEMBL d
1 comment
Read more