New Drug Approvals 2014 - Pt. XI - Idelalisib (Zydelig™)

ATC Code: L01XX47

Wikipedia: Idelalisib

On July 23rd the FDA approved Zydelig (idelalisib, GS-1101), as an orally-delivered drug to treat patients with three types of blood cancers.
• Relapsed chronic lymphocytic leukemia (CLL)
• Relapsed follicular B-cell, non-Hodgkin lymphoma (FL)
• Relapsed small lymphocytic lymphoma (SLL)

Blood cancer

The three main categories of blood cancer are leukemia, lymphoma and myeloma. Lymphoma is also split into two types: Hodgkin lymphoma and non-Hodgkin lymphoma. Both leukemia and myeloma occur in the bone marrow, whilst lymphoma is a cancer that is isolated to the lymphatic system. Acute leukemia is where there is an abundance of underdeveloped white blood cells that can’t function properly and chronic leukemia is where there are just far too many white blood cells, which is just as bad as having too few. Myeloma is where the plasma cells form tumours in the bone marrow.

Idelalisib

This drug is a phosphoinositide 3-kinase inhibitor, which works by blocking P110σ (CHEMBL3130, Uniprot:O00329), the delta isoform of the phosphoinositide 3-kinase enzyme, encoded in humans by the PIK3CD gene. This isoform plays a role in B-cell development, proliferation and function and is expressed predominantly in leukocytes.

Mode of action

Idelalisib works on patients by inhibiting the PI3 kinase delta isoform (PI3Kδ), which plays an important role in malignant lymphocyte survival. It is the delta and gamma forms that are specific to the hematopoietic system. This treatment impairs the normal tracking of CLL lymph nodes. It can be used in conjunction with Rituxan (rituximab), an existing blood cancer treatment, for relapsed CLL and on its own for FL and SLL.

Clinical trials

Clinical trials were carried out on 220 patients, with relapsed CLL, who were not healthy enough, due to co-existing medical conditions or damage from previous chemotherapy, to receive cytotoxic therapy. Patients were administered either idelalisib plus rituximab or a placebo and rituximab. Most of these patients were 65 years of age or older.

After 24 weeks, 93% of the group who had taken the combination treatment were disease progression-free, compared to only 46% of the group who had received the placebo and rituximab combination.

After 12 months, 90% of the dual drug combination group were alive, compared to 80% of the placebo-containing group. [NCI]

Indication and Warnings

This drug can be used in combination with rituximab or on its own, indicated for patients with relapsed conditions. There are several warnings for idelalisib, including hepatotoxicity, pneumonitis (fatal and serious), intestinal perforation and embyro-fetal toxicity. [FDA]

Trade Names

Idelalisib was developed by Gildead Sciences and is marketed under the name Zydelig.

Comments

SureChEMBL Available Now

Followers of the ChEMBL group's activities and this blog will be aware of our involvement in the migration of the previously commercially available SureChem chemistry patent system, to a new, free-for-all system, known as SureChEMBL. Today we are very pleased to announce that the migration process is complete and the SureChEMBL website is now online. SureChEMBL provides the research community with the ability to search the patent literature using Lucene-based keyword queries and, much more importantly, chemistry-based queries. If you are not familiar with SureChEMBL, we recommend you review the content of these earlier blogposts here and here . SureChEMBL is a live system, which is continuously extracting chemical entities from the patent literature. The time it takes for a new chemical in the patent literature to become searchable in the SureChEMBL system is 1-2 days (WO patents can sometimes take a bit longer due to an additional reprocessing step). At time of writi

New SureChEMBL announcement

(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

ChEMBL & SureChEMBL anniversary symposium

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

ChEMBL 34 is out!

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.

RDKit, C++ and Jupyter Notebook

Fancy playing with RDKit C++ API without needing to set up a C++ project and compile it? But wait... isn't C++ a compiled programming language? How this can be even possible? Thanks to Cling (CERN's C++ interpreter) and xeus-cling jupyter kernel is possible to use C++ as an intepreted language inside a jupyter notebook! We prepared a simple notebook showing few examples of RDKit functionalities and a docker image in case you want to run it. With the single requirement of docker being installed in your computer you'll be able to easily run the examples following the three steps below: docker pull eloyfelix/rdkit_jupyter_cling docker run -d -p 9999:9999 eloyfelix/rdkit_jupyter_cling open http://localhost:9999/notebooks/rdkit_cling.ipynb in a browser

The ChEMBL-og

Search This Blog