Umbralisib

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Structural formula
Structure of umbralisib
General
Non-proprietary name Umbralisib
other names
  • 2 - [(1 S ) -1- {4-Amino-3- [3-fluoro-4- (propan-2-yloxy) phenyl] -1 H -pyrazolo [3,4-d] pyrimidin-1-yl } ethyl] -6-fluoro-3- (3-fluorophenyl) -4 H -1-benzopyran-4-one
  • RP-5264
  • TGR-1202
Molecular formula C 31 H 24 F 3 N 5 O 3
External identifiers / databases
CAS number 1532533-67-7
PubChem 72950888
ChemSpider 34979945
DrugBank DB14989
Wikidata Q27088612
properties
Molar mass 571.55 g mol −1
safety instructions
GHS hazard labeling
07 - Warning 09 - Dangerous for the environment

Danger

H and P phrases H: 302-410
P: 264-270-273-301 + 310-330-391-501
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Umbralisib is a drug from the group of PI3K inhibitors and is used in cancer treatment. As Ukoniq ( TG Therapeutics ), it was approved in the United States in 2021 for the oral treatment of certain forms of marginal zone lymphoma and follicular lymphoma .

Mechanism of action

Umbralisib is an inhibitor of several kinases . In vitro inhibition was phosphoinositide 3-kinase delta (PIK3δ) and the casein kinase 1 epsilon (CK1ε) is shown. They are key enzymes in signaling pathways for cell growth and cell metabolism. PI3Kδ is in normal and malignant B cells expressed , CK1ε is on the pathogenesis involved of cancer cells. Umbralisib inhibited in vitro the cell proliferation , the CXCL12 -mediated cell adhesion and CCL19 -mediated cell migration in lymphoma cell lines.

application

Umbralisib was approved in the United States in February 2021 for the following indications:

  • Recurrent or refractory marginal zone lymphoma (MCL) in adult patients who have received at least one prior anti- CD20 -based regimen;
  • Recurrent or refractory follicular lymphoma (FL) in adult patients who have previously received at least three lines of systemic therapy.

The active ingredient is used pharmaceutically as a salt of p-toluenesulphonic acid , umbralisibosilate . The preparation is given as a tablet.

Side effects and restrictions on use

The most common side effects observed were intestinal discomfort with diarrhea, vomiting, abdominal pain, nausea, decreased appetite, fatigue, musculoskeletal pain, anemia , thrombocytopenia , neutropenia , upper respiratory tract infection and rash.

In addition, the serum levels of creatinine and transaminases were increased.

Studies

Approval was based on two-armed cohorts an open, multi-center multi- cohort study of 69 patients with MCL who had at least one prior therapy including an anti-CD20 based therapy, and systemic in 117 patients with FL after at least two previous Therapies. Patients received umbralisib orally once daily until disease progression or until unacceptable toxicity occurred.

Efficacy was assessed by the overall response rate ( overall response rate ORR) and duration of response ( duration of response , DOR) using modified criteria of the International Working Group in 2007, which were evaluated by an independent review panel.

miscellaneous

Umbralisib after Idelalisib , Copanlisib , Duvelisib and Alpelisib another representative of the PI3K inhibitors. In general, kinase inhibitors are among the most effective drugs in targeted cancer therapy.

Individual evidence

  1. ↑ a b Biomol.de: TGR-1202 | CAS 1532533-67-7 | Cayman Chemical | Biomol.de , accessed on April 3, 2021
  2. ↑ a b FDA grants accelerated approval to umbralisib for marginal zone lymphoma and follicular lymphoma , FDA,
  3. ↑ a b Ukoniq Prescribing Information , FDA, February 5, 2021.
  4. ↑ External identifiers from or database links to Umbralisibtosilat : CAS Number: 1532533-72-4 , PubChem : 86707828 , ChemSpider : 58790036 , Wikidata : Q106269240 .
  5. ↑ S. Klaeger et al .: The target landscape of clinical kinase drugs . In: Science . 2017, doi : 10.1126 / science.aan4368 .