Idelalisib structure
Clinical data
Trade namesZydelig
Other namesGS-1101, CAL-101
License data
  • AU: D
Routes of
By mouth (tablets)
ATC code
Legal status
Legal status
  • US: ℞-only
  • EU: Rx-only [1]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding>84%[2]
MetabolismAldehyde oxidase (~70%), CYP3A4 (~30%);[3] UGT1A4 (minor)
MetabolitesGS-563117 (inactive in vitro)
Onset of actionTmax = 1.5 hours
Elimination half-life8.2 hours
ExcretionFeces (78%), urine (14%)
  • 5-Fluoro-3-phenyl-2-[(1S)-1-(7H-purin-6-ylamino)propyl]-4(3H)-quinazolinone
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.235.089 Edit this at Wikidata
Chemical and physical data
Molar mass415.432 g·mol−1
3D model (JSmol)
  • CC[C@H](Nc1ncnc2nc[nH]c12)c4nc3cccc(F)c3c(=O)n4c5ccccc5
  • InChI=1S/C22H18FN7O/c1-2-15(28-20-18-19(25-11-24-18)26-12-27-20)21-29-16-10-6-9-14(23)17(16)22(31)30(21)13-7-4-3-5-8-13/h3-12,15H,2H2,1H3,(H2,24,25,26,27,28)/t15-/m0/s1

Idelalisib, sold under the brand name Zydelig, is a medication used to treat certain blood cancers.[2][1]

The substance acts as a phosphoinositide 3-kinase inhibitor; more specifically, it blocks P110δ, the delta isoform of the enzyme phosphoinositide 3-kinase.[4][5] It was developed by Gilead Sciences. Idelalisib had annual sales of $168 million (USD) during the year of 2016, up from $132 million (USD) in 2015.[6]

Medical uses

Idelalisib is a second-line drug for patients whose chronic lymphocytic leukemia (CLL) has relapsed. Used in combination with rituximab,[7] idelalisib is to be used in patients for whom rituximab alone would be considered appropriate therapy due to other existing medical conditions.[7] It appears to be effective and leads to improvement of lymphadenopathy and splenomegaly. However, the lymphocyte counts take longer to decrease to normal levels with idelalisib. It is not recommended as a first-line treatment.[2]

It is also approved for the treatment of follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic lymphoma (SLL), both in patients who have received at least two prior systemic therapies.[2]

Adverse effects

Clinical symptoms include diarrhea, fever, fatigue, nausea, cough, pneumonia, abdominal pain, chills and rash. Laboratory abnormalities may include: neutropenia, hypertriglyceridemia, hyperglycemia and elevated levels of liver enzymes. Idelalisib's safety and effectiveness to treat relapsed FL and relapsed SLL were established in a clinical trial with 123 participants with slow-growing (indolent) non-Hodgkin lymphomas. All participants were treated with idelalisib and were evaluated for complete or partial disappearance of their cancer after treatment (objective response rate, or ORR). Results showed 54% of participants with relapsed FL and 58% of participants with SLL experienced ORR.[8]

The U.S. label for idelalisib has a boxed warning describing toxicities that can be serious and fatal, including liver toxicity, severe diarrhea, colon inflammation, lung tissue inflammation (pneumonitis) and intestinal perforation, and the manufacturer was required to put in place a Risk Evaluation and Mitigation Strategy (REMS) under which the risk of toxicities would be managed.[9]

In March 2016, as reports were made from three ongoing clinical trials of serious adverse events and deaths, mostly due to infections, the European Medicines Agency opened a review of the drug and its risks.[10] On March 21, 2016 Gilead Sciences (the manufacturer of idelalisib) alerted healthcare providers about decreased overall survival and increased risk of serious infections in patients with CLL and indolent non-Hodgkin lymphoma (iNHL) treated with idelalisib.[11] The company also disclosed that it stopped six clinical trials in patients with CLL, SLL and iNHL due to an increased rate of adverse events, including deaths.[12] In 2016, the EMA recommended that people on idelalisib should be given medication against the lung infection Pneumocystis jirovecii pneumonia and this should be continued for up to 6 months after idelalisib has stopped. In addition, people should be monitored for signs of infection.[13]


Mechanism of action

PI3Kδ is expressed in normal and malignant B-cells. By inhibiting it, idelalisib induces apoptosis and prevents proliferation in cell lines derived from malignant B-cells and in primary tumor cells. It also inhibits several cell signaling pathways, including B-cell receptor (BCR) signaling and the CXCR4 and CXCR5 signaling, which are involved in the trafficking and homing of B-cells to the lymph nodes and bone marrow.[2] Idelalisib reduces the levels of CD20 on the surface of malignant B lymphocytes by interfering with the IL4-STAT6,[14] which might explain some of its repressive effects on the biology of B cells, but also impair its efficacy in combination with anti-CD20 antibodies (rituximab, ofatumumab etc.).

Binding profile

Idelalisib is a competitive inhibitor of the ATP binding site of the PI3Kδ catalytic domain. Its in vitro potency and selectivity relative to the other Class I PI3K isoforms is the following:[15]

PI3K isoform IC50, nM IC50-based PI3Kδ-fold selectivity
PI3Kα 8,600 453
PI3Kβ 4,000 211
PI3Kγ 2,100 110
PI3Kδ 19 1



In July 2014, the FDA and EMA granted idelalisib approval to treat different types of leukemia.[8][16] The FDA is also granted approval for idelalisib to treat patients with relapsed follicular B-cell non-Hodgkin lymphoma and relapsed small lymphocytic lymphoma. Idelalisib is intended to be used in patients who have received at least two prior systemic therapies.


  1. ^ a b "Zydelig EPAR". European Medicines Agency (EMA). Retrieved 21 October 2020.
  2. ^ a b c d e "Zydelig- idelalisib tablet, film coated". DailyMed. 22 October 2018. Retrieved 21 October 2020.
  3. ^ "Clinical Pharmacology and Biopharmaceutics Review: Zydelig (idelalisib)" (PDF). U.S. Food and Drug Administration. p. 6. Retrieved 15 April 2016.
  4. ^ Spreitzer H (13 May 2013). "Neue Wirkstoffe – Ibrutinib und Idelalisib". Österreichische Apothekerzeitung (in German) (10/2013): 34.
  5. ^ Wu M, Akinleye A, Zhu X (May 2013). "Novel agents for chronic lymphocytic leukemia". Journal of Hematology & Oncology. 6: 36. doi:10.1186/1756-8722-6-36. PMC 3659027. PMID 23680477.
  6. ^ "Annual Sales of Idelalisib reported using PharmaCompass' compilation of Annual Reports of Global Pharmaceutical Companies". Pharmacompass. Retrieved January 21, 2019.
  7. ^ a b Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, et al. (March 2014). "Idelalisib and rituximab in relapsed chronic lymphocytic leukemia". The New England Journal of Medicine. 370 (11): 997–1007. doi:10.1056/NEJMoa1315226. PMC 4161365. PMID 24450857.
  8. ^ a b "FDA approves Zydelig for three types of blood cancers" (Press release). Food and Drug Administration. July 23, 2014.
  9. ^ "Press Announcements — FDA approves Zydelig for three types of blood cancers". Retrieved 2016-03-14.
  10. ^ "European Medicines Agency — News and Events — EMA reviews cancer medicine Zydelig". Retrieved 2016-03-14.
  11. ^ "Important Drug Warning: Decreased Overall Survival and Increased Risk of Serious Infections in Patients Receiving ZYDELIG (idelalisib)" (PDF). Gilead Sciences, Inc. March 21, 2016. Retrieved 19 April 2016.
  12. ^ "Drug Safety and Availability — FDA Alerts Healthcare Professionals About Clinical Trials with Zydelig (idelalisib) in Combination with Other Cancer Medicines". FDA Center for Drug Evaluation and Research. Retrieved 19 April 2016.
  13. ^ "CHMP confirms recommendations for use of Zydelig". European Medicines Agency (EMA). 15 September 2016.
  14. ^ Sandova V, Pavlasova GM, Seda V, Cerna KA, Sharma S, Palusova V, Brychtova Y, Pospisilova S, Fernandes SM, Panovska A, Doubek M, Davids MS, Brown JR, Mayer J, Mraz M (July 2021). "IL4-STAT6 signaling induces CD20 in chronic lymphocytic leukemia and this axis is repressed by PI3Kdelta inhibitor idelalisib". Haematologica. 106 (11): 2995–2999. doi:10.3324/haematol.2021.278644. PMC 8561290. PMID 34196167.
  15. ^ "Committee for Medicinal Products for Human Use Assessment Report: Zydelig (idelalisib)" (PDF). European Medicines Agency. p. 17. Retrieved 19 April 2016.
  16. ^ "European Medicines Agency recommends approval of two new treatment options for rare cancers" (Press release). European Medicines Agency. July 25, 2014.