Advances in PI3Kδ selective inhibitors

XIN Minhang; ZHANG Sanqi

doi:10.11665/j.issn.1000-5048.20160501

Journal of China Pharmaceutical University > 2016 > 47(5): 503-510. > DOI: 10.11665/j.issn.1000-5048.20160501

XIN Minhang, ZHANG Sanqi. Advances in PI3Kδ selective inhibitors[J]. Journal of China Pharmaceutical University, 2016, 47(5): 503-510. DOI: 10.11665/j.issn.1000-5048.20160501

Citation:

XIN Minhang, ZHANG Sanqi. Advances in PI3Kδ selective inhibitors[J]. Journal of China Pharmaceutical University, 2016, 47(5): 503-510. DOI: 10.11665/j.issn.1000-5048.20160501

Citation:

XIN Minhang, ZHANG Sanqi. Advances in PI3Kδ selective inhibitors[J]. Journal of China Pharmaceutical University, 2016, 47(5): 503-510. DOI: 10.11665/j.issn.1000-5048.20160501

PDF (2048 KB)

Advances in PI3Kδ selective inhibitors

More Information

Graphical Abstract

Abstract

Abstract

Phosphoinositide 3-kinase(PI3K), a key regulator in the PI3K/AKT/mTOR signaling pathway, plays a critical role in regulation of cell growth, differentiation, metastasis apoptosis, and angiogenesis processes. Abnormal activation of PI3K is closely related to the development of many types of human cancers. PI3Kδ is an important isoform of PI3K family, mainly expressed in leukocytes, which makes it an attractive target for the treatment of hematological malignancies. Great efforts in both industry and academia have been made to develop PI3Kδ selective inhibitors as anti-cancer agents. This review attempts to provide an overview of recent advances in the research of PI3Kδ selective inhibitors, fueling the progress of the ideal selective PI3Kδ inhibitors in the future.
- PI3Kδ,
- inhibitors,
- hematological malignancies,
- advance

FullText(HTML)

References (23)

References

[1]	Fruman DA,Rommel C.PI3K and cancer:lessons,challenges and opportunities[J].Nat Rev Drug Disc,2014,13(2):140-156.
[2]	Thorpe LM, Yuzugullu H, Zhao JJ. PI3K in cancer: divergent roles of isoforms,modes of activation and therapeutic targeting[J].Nat Rev Canner,2015,15(1):7-24.
[3]	Puri KD,Di Paolo JA,Gold MR.B-cell receptor signaling inhibitors for treatment of autoimmune inflammatory diseases and B-cell malignancies[J].Int Rev Immunol,2013,32(4):397-427.
[4]	Puri KD, Gold MR. Selective inhibitors of phosphoinositide 3-kinase delta:modulators of B-cell function with potential for treating autoimmune inflammatory diseases and B-cell malignancies[J].Front Immunol,2012,3:256.
[5]	Angulo I,Vadas O,Garcon F.Phosphoinositide 3-kinase δ gene mutation predisposes to respiratory infection and airway damage[J].Science,2013,342(6160):866-871.
[6]	Shao T,Wang J,Chen JG,et al.Discovery of 2-methoxy-3-phenylsufonamino-5-(quinazolin-6-yl or quinolin-6-yl)benzamides as novel PI3K inhibitors and anticancer agents by bioisostere[J].Eur J Med Chem,2014,75:96-105.
[7]	Wei M,Wang X,Song Z,et al.Targeting PI3Kδ:emerging therapy for chronic lymphocytic leukemia and beyond[J].Med Res Rev,2015,35(4):720-752.
[8]	Venable JD, Ameriks MK. Small molecule inhibitors of phosphoinositide 3-kinase(PI3K)δ and γ[J].Curr Top Med Chem,2009,9(8):738-753.
[9]	Norman P.Selective PI3Kδ inhibitors,a review of the patent literature[J].Expert Opin Ther Pat,2011,21(11):1773-1790.
[10]	Norman P.Evaluation of WO201313136076:two crystalline forms of the phosphatidylinositol 3-kinase-δ inhibitor RV-1729[J].Expert Opin Ther Pat,2013,24(4):471-475.
[11]	Norman P. Evaluation of WO2013116562A, an orally active PI3Kδ inhibitor for the treatment of asthma[J].Expert Opin Ther Pat,2014,24(5):603-607.
[12]	Markham A.Idelalisib:first global approval[J].Drugs,2014,74(14):1701-1707.
[13]	Fruman DA,Cantley LC.Idelalisib a PI3Kδ inhibitor for B-cell cancers[J].N Engl J Med,2014,370(11):1061-1062.
[14]	Okkenhaug K.Two birds with one stone:dual p110δ and p110γ inhibition[J].Chem Biol,2013,20(11):1309-1310.
[15]	TG Therapeutics.TG-1101(Ublituximab)references[EB/OL].http://www.tgtherapeutics.com/pipeline/publications.cfm.
[16]	Vakkalanka S,Viswanadha S,Gaudio E,et al.Dual PI3Kδ/γ inhibition by RP6530 induces apoptosis and cytotoxicity in B-lymphoma cells[J].Blood,2013,122(21):4411.
[17]	Cushing TD,Hao X,Shin Y,et al.Discovery and in vivo evaluation of(s)-N-(1-(7-fluoro-2-(pyridine-2-yl)quinolin-3-yl)ethyl)-9H-purin-6-amine(AMG319)and related PI3Kδ inhibitors for inflammation and autoimmune disease[J].J Med Chem,2015,58(1):480-511.
[18]	Safina BS,Baker S,Baumgardner M,et al.Discovery of novel PI3-kinase δ specific inhibitors for the treatment of rheumatoid arthritis:taming CYP3A4 time-dependent inhibition[J].J Med Chem,2012,55(12):5887-5900.
[19]	Murray JM,Sweeney ZK,Chan BK,et al.Potent and highly selective benzimidazole inhibitors of PI3-kinase delta[J].J Med Chem,2012,55(17):7686-7695.
[20]	Safina BS,Sweeney ZK,Li J,et al.Identification of GNE-293,a potent and selective PI3Kδ inhibitor:navigating in vitro genotoxicity while improving potency and selectivity[J].Bioorg Med Chem Lett,2013,23(17):4953-1959.
[21]	Down K, Amour A, Baldwin IR, et al. Optimization of novel indazoles as highly potent and selective inhibitors of phosphoinositide 3-kinase δ for the treatment of respiratory disease[J].J Med Chem,2015,58(18):7381-7399.
[22]	Haselmayer P,Camps M,Muzerelle M.Characterization of novel of PI3Kδ inhibitors as potentical therapeutics for SLE and lupus nephritis in pre-clinical studies[J].Front Immunol,2014,5:233.
[23]	Cushing TD,Metz DP,Whittington DA,et al.PI3Kδ and PI3Kγ as targets for autoimmune and inflammatory diseases[J].J Med Chem,2012,55(20):8559-8581.

Cited By

Get Citation

PDF

XML

Article views (1408) PDF downloads (2696)

Turn off MathJax

Article Contents

Abstract

References

Advances in PI3Kδ selective inhibitors

Abstract

References

Catalog

Export File

Citation

Format

Content