Copanlisib: Novel PI3K Inhibitor for the Treatment of Lymphoma

Abstract

: Lymphoma refers to a specialized category of blood cancers which is characterized by lymph node enlargement, reduced body weight, prolonged tiredness and fever associated with sweats. Traditional treatment strategies involve chemotherapy, radiation therapy, targeted therapy, and surgery. Copanlisib has emerged as a very potent drug which acts through inhibiting PI3K enzyme. FDA has approved it for specific treatment of follicular Lymphoma in September 2017. Copanlisib induces tumor cell death along with prevention of proliferation of dominant malignant β-cells. Copanlisib has a large volume of distribution i.e. 871L (%CV 47.4), plasma protein binding upto 15.8%, plasma half-life(t1/2) of 39.1h and mean systemic plasma clearance 18.9 L/h (%CV 51.2). In the present review various aspects related to Copanlisib have been summarized which include pathophysiology, synthetic strategy, pharmacokinetics, pharmacodynamics and clinical studies. A special emphasis is given on various reported adverse effect and in silico/ in vivo studies conducted on Copanlisib.

Copanlisib promotes growth inhibition and apoptosis by modulating the AKT/FoxO3a/PUMA axis in colorectal cancer

“…The toxicity associated with copanlisib compares well with that associated with other agents of the same class, and copanlisib is associated with fewer and less severe gastrointestinal toxicities than idelalisib 10,13 . Copanlisib is now approved by the FDA for relapsed FL patients after at least 2 systemic therapies due to the results of a phase 2 study showing an ORR of 59% and a CR of 14% 14 .…”

Exosome-based delivery of RNAi leads to breast cancer inhibition

“…Therefore, tremendous efforts are being employed to develop anticancer strategies targeting the PAM pathway. Currently, five different inhibitors targeting the PAM oncogenic signaling pathway in diverse cancers J o u r n a l P r e -p r o o f have been approved by FDA [28][29][30][31][32]. Within the breast cancer therapy scenario, alpelisib (BYL-719), a class I PIK3 α-isoform targeted inhibitor, was approved in the treatment of hormone receptor positive cases with a tremendous potential in advanced tumor with PIK3CA mutations [31,33]; and everolimus, an allosteric mTORC1 inhibitor, that improved the patient outcomes after endocrine therapy in hormone and HER 2…”

Cardiovascular Toxicity of Antineoplastic Treatments in Hematological Diseases: Focus on Molecular Mechanisms to Improve Therapeutic Management

“…The PI3Kδ specific inhibitor idelalisib is the first FDA approved PI3K inhibitor to treat relapsed CLL, follicular B-cell non-Hodgkin lymphoma, and small lymphocytic lymphoma [ 169 ]. Several second-generation PI3K inhibitors have been formulated and are presently undergoing clinical assessment including isoform-specific inhibitors characterized by enhanced selectivity, inhibitors designed to target multiple PI3K isoforms with a synergistic impact (duvelisib, a dual inhibitor of PI3Kδ and γ), and pan-class I inhibitors (Copanlisib) [ 170 ].…”