Selective PI3Kδ inhibitors, a review of the patent literature

Expert Opinion on Therapeutic Patents

Volumn 21, Issue 11, 2011, Pages 1773-1790

  Norman, Peter ^a  

^a NORMAN CONSULTING   (United Kingdom)

Author keywords

AMG 319; CAL 101; Cancer; Inflammation; Leukaemia; Leukocyte; Lymphoma; PI3K inhibitor; PI3Kdelta inhibitor; Rheumatoid arthritis

Indexed keywords

5 (6 QUINOXALINYLMETHYLENE) 2,4 THIAZOLIDINEDIONE; 9 (1 ANILINOETHYL) 7 METHYL 2 MORPHOLINOPYRIDO[1,2 A]PYRIMIDIN 4 ONE; AMG 319; AZD 6482; BYL 719; CAL 101; CAL 120; CAL 263; CH 5132799; ETP 00046321; ETP 00047022; EXEL 4251; EXEL 5080; GS 1101; INK 1117; KAR 4139; KAR 4141; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE DELTA INHIBITOR; PHOSPHATIDYLINOSITOL 3 KINASE GAMMA; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PICTRELISIB; PIK 75; PWT 33597; RP 5002; RP 5090; RP 5237; SB 2343; UNCLASSIFIED DRUG; UNINDEXED DRUG; XL 499;

ARTICLE; ASTHMA; B CELL LYMPHOMA; CHRONIC OBSTRUCTIVE LUNG DISEASE; DNA SEQUENCE; DRUG EFFICACY; DRUG STRUCTURE; GENE MUTATION; HODGKIN DISEASE; HUMAN; IC 50; INFLAMMATION; LEUKEMIA; MULTIPLE MYELOMA; NEOPLASM; NONHUMAN; PATENT; PROTEIN EXPRESSION; SOLID TUMOR; THROMBOSIS; UPREGULATION;

ANIMALS; ANTI-INFLAMMATORY AGENTS; ANTINEOPLASTIC AGENTS; DRUG DELIVERY SYSTEMS; DRUG DESIGN; ENZYME INHIBITORS; HEMATOLOGIC NEOPLASMS; HUMANS; INFLAMMATION; ISOENZYMES; PATENTS AS TOPIC; PHOSPHATIDYLINOSITOL 3-KINASES;

EID: 80054947365     PISSN: 13543776     EISSN: 17447674     Source Type: Journal    
DOI: 10.1517/13543776.2011.629606     Document Type: Article

References (90)

1. Vanhaesebroeck B, Waterfield MD. Signaling by distinct classes of phosphoinositide 3-kinases. Exp Cell Res 1999;253(1):239-54
2. Holmes D. PI3K pathway inhibitors approach junction. Nat Rev Drug Discov 2011;10(8):563-4
3. Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 2009;8(8):627-44
4. Norman P. The PI3K/Akt/mTOR Cascade - A Pipeline Report, CHI Insight Pharma Report; 2011
5. Vlahos CJ, Matter WF, Hui KY, Brown RF. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1- benzopyran-4-one (LY294002). J Biol Chem 1994;269(7):5241-8
6. Powis G, Bonjouklian R, Berggren MM, et al. Wortmannin, a potent and selective inhibitor of phosphatidylinositol-3-kinase. Cancer Res 1994;54(9):2419-23
7. Bowles DW, Jimeno A. New phosphatidylinositol 3-kinase inhibitors for cancer. Expert Opin Investig Drugs 2011;20(4):507-18
8. Shuttleworth SJ, Silva AF, Cecil RL, et al. Progress in the preclinical discovery and clinical development of class I and dual class I/IV phosphoinositide 3-kinase (PI3K) inhibitors. Curr Med Chem 2011;18:2686-714
9. Zhao L, Vogt PK. Class I PI3K in oncogenic cellular transformation. Oncogene 2008;27(41):5486-96
10. Jia S, Liu Z, Zhang S, et al. Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis. Nature 2008;454(7205):776-9
11. Guillermet-Guibert J, Bjorklof K, Salpekar A, et al. The p110beta isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110gamma. Proc Natl Acad Sci USA 2008;105(24):8292-7 (Pubitemid 351904749)
12. Liu L, Puri KD, Penninger JM, Kubes P. Leukocyte PI3Kgamma and PI3Kdelta have temporally distinct roles for leukocyte recruitment in vivo. Blood 2007 Aug 15;110:(4):1191-8 (Pubitemid 47281416)
13. Thomas MJ, Smith A, Head DH, et al. Airway inflammation: chemokine-induced neutrophilia and the class I phosphoinositide 3-kinases. Eur J Immunol 2005 Apr;35(4):1283-91 (Pubitemid 40542236)
14. Kang S, Denley A, Vanhaesebroeck B, et al. Oncogenic transformation induced by the p110beta, -gamma, and -delta isoforms of class I phosphoinositide 3-kinase. Proc Natl Acad Sci USA 2006;103:1289-94 (Pubitemid 43191158)
15. Rommel C, Camps M, Ji H. PI3K delta and PI3K gamma: partners in crime in inflammation in rheumatoid arthritis and beyond? Nat Rev Immunol 2007;7(3):191-201
16. Kulkarni S, Sitaru C, Jakus Z, et al. PI3Kbeta plays a critical role in neutrophil activation by immune complexes. Sci Signal 2011;4(168):ra23
17. Vanhaesebroeck B, Welham MJ, Kotani K, et al. P110delta, a novel phosphoinositide 3-kinase in leukocytes. Proc Natl Acad Sci USA 1997;94(9):4330-5 (Pubitemid 27194241)
18. Ali K, Camps M, Pearce WP, et al. Isoform-specific functions of phosphoinositide 3-kinases: p110 delta but not p110 gamma promotes optimal allergic responses in vivo. J Immunol 2008;180(4):2538-44
19. Marwick JA, Chung KF, Adcock IM. Phosphatidylinositol 3-kinase isoforms as targets in respiratory disease. Ther Adv Respir Dis 2010;4(1):19-34
20. Fung-Leung WP. Phosphoinositide 3-kinase delta (PI3Kdelta) in leukocyte signaling and function. Cell Signal 2011;23(4):603-8
21. Sujobert P, Bardet V, Cornillet-Lefebvre P, et al. Essential role for the p110delta isoform in phosphoinositide 3-kinase activation and cell proliferation in acute myeloid leukemia. Blood 2005;106(3):1063-6 (Pubitemid 41076455)
22. AstraZeneca AB. Enantiomerically pure (-) 2-[1-(7-methyl-2-(morpholin-4- yl)-4- oxo-4h-pyrido[1,2-a]pyrimidin-9-yl) ethylamino]benzoic acid, its use in medical therapy, and a pharmaceutical composition comprising it. WO2009093972; 2009
23. Workman P, Clarke PA, Raynaud FI, van Montfort RL. Drugging the PI3 kinome: from chemical tools to drugs in the clinic. Cancer Res 2010;70(6):2146-57
24. Zheng Z, Amran SI, Thompson PE, Jennings IG. Isoform selective inhibition of phosphoinositide 3-kinase: identification of a new region of non-conserved amino acids critical for p110{alpha} inhibition. Mol Pharmacol 2011;In press
25. Frazzetto M, Suphioglu C, Zhu J, et al. Dissecting isoform selectivity of PI3K inhibitors: the role of non-conserved residues in the catalytic pocket. Biochem J 2008;414(3):383-90
26. Berndt A, Miller S, Williams O, et al. The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors. Nat Chem Biol 2010;6(2):117-24
27. Sadhu C, Dick K, Tino WT, Staunton DE. Selective role of PI3K delta in neutrophil inflammatory responses. Biochem Biophys Res Commun 2003;308(4):764-9 (Pubitemid 36976527)
28. Herman SE, Gordon AL, Wagner AJ, et al. Phosphatidylinositol 3-kinase-delta inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals. Blood 2010;116(12):2078-88
29. Mattheakis L, Kearney P, Jaeger C, et al. PI3Kdelta: discovery of potent and selective inhibitors for treating hematopoietic malignancies. 22nd EORTC-NCI-AACR symposium on "Molecular targets and Cancer Therapeutics"; 2010
30. ICOS Corp. Phosphatidylinositol 3-kinase P110 delta catalytic subunit. WO1998023760; 1998
31. ICOS Corp. Phosphatidyl inositol 3-kinase delta binding partner. WO2001085986; 2001
32. ICOS Corp. Inhibitors of human phosphatidyl-inositol 3-kinase delta. WO2003035075; 2003
33. ICOS Corp. Method of inhibiting immune responses stimulated by an endogenous factor. WO2005016348; 2005
34. ICOS Corp. Methods of inhibiting leukocyte accumulation. WO2005016349; 2005
35. Vanderbilt University, ICOS Corp. Phosphoinositide 3-kinase delta selective inhibitors for inhibiting angiogenesis. WO2005112935; 2005
36. ICOS Corp. Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta. WO2005113556; 2005
37. Eli Lilly & Co. Thienopyrimidinones for treatment of inflammatory disorders and cancers. WO2008064018; 2008
38. ICOS Corp. Inhibitors of human phosphatidyl-inositol 3-kinase delta. WO2009064802; 2009
39. Calistoga Pharmaceuticals, Inc. Therapies for hematologic malignancies. WO2010057048; 2010
40. Calistoga Pharmaceuticals, Inc. Methods of treatment for solid tumors. WO2010123931; 2010
41. Calistoga Pharmaceuticals, Inc. Atropisomers of 2-purinyl-3- tolylquinazolinone derivatives and methods of use. WO2010111432; 2010
42. Calistoga Pharmaceuticals, Inc. Treatment of liver disorders with PI3K inhibitors. WO2011011550; 2011
43. Norman P. Novel 1,5-naphthyridine PI3Kdelta inhibitors, an evaluation of. WO2011075628; 2011
44. Amgen, Inc. Heterocyclic compounds and their uses. WO2011075628; 2011
45. Amgen, Inc. Derivatives of quinoline or benzopyrazine and their uses for the treatment of (Inter Alia) inflammatory diseases, autoimmune diseases or various kinds of cancer. WO2008118454; 2008
46. Amgen, Inc. delta3- Substituted quinoline or quinoxaline derivatives and their use as phosphatidylinositol 3-kinase (PI3K) inhibitors. WO2008118455; 2008
47. Amgen, Inc. Heterocyclic compounds and their uses. WO2008118468; 2008
48. Amgen, Inc. Polycyclic derivatives of pyridine and their use in the treatment Of (Inter Alia) rheumatoid arthritis and similar diseases. WO2010151740; 2010
49. Amgen, Inc. Heterocyclic compounds and their uses as inhibitors of PI3K activity. WO2010151737; 2010
50. Amgen, Inc. 4H-Pyrido[1,2-a]pyrimidin- 4-one derivatives as PI3K inhibitors. WO2010151735; 2010
51. Amgen, Inc. Heterocyclic compounds and their uses. WO2010151791; 2010
52. Knight ZA, Gonzalez B, Feldman ME, et al. A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell 2006;125(4):733-47
53. Intellikine, Inc. Certain chemical entities, compositions and methods. WO2009088990; 2009
54. Intellikine, Inc. Heterocyclic kinase inhibitors. WO2010036380; 2010
55. Intellikine, Inc. Heterocyclic compounds and uses thereof. WO2010129816; 2010
56. Intellikine, Inc. Certain chemical entities, compositions and methods. WO2011008302; 2011
57. Intellikine, Inc. Methods and compositions for treatment of ophthalmic conditions. WO2010059593; 2010
58. Rommel C. Taking PI3Kdelta and PI3Kgamma one step ahead: dual active PI3Kdelta/gamma inhibitors for the treatment of immune-mediated inflammatory diseases. Curr Top Microbiol Immunol 2010;346:279-99
59. Incyte Corp. Substituted fused aryl and heteroaryl derivatives as PI3K inhibitors. WO2011075630; 2011
60. Incyte Corp. Substituted heteroaryl fused derivatives as PI3K inhibitors. WO2011075643; 2011
61. Incyte Corp. Pyrimidinones as PI3K inhibitors. WO2011008487; 2011
62. Liao CH, Pei-Yuan JS, Patel V, et al. RO2492, A phosphoinositide-288- kinase D inhibitor, shows inhibitory effects in a variety of human cell types and suppresses collagen-induced arthritis in mice. Arthritis Rheum 2010;62(Suppl 10):288
63. Piramed Ltd. Pharmaceutical compounds. WO2006046031; 2006
64. Piramed Ltd. Pharmaceutical compounds. WO2006046035; 2006
65. Ludwig Institute For Cancer Research et al. Pyrimidine derivatives for the treatment of cancer. WO2007042810; 2007
66. F. Hoffmann-La Roche AG. The Institute of cancer research, pharmaceutical compounds. WO2008125833; 2008
67. F. Hoffmann-La Roche AG. The Institute of cancer research, 2- morpholin-4-yl-pyrimidines as PI3K inhibitors. WO2008125835; 2008
68. F. Hoffmann-La Roche AG. The Institute of cancer research, pyrimidine derivatives as inhibitors of phosphatidylinositol-3-kinase. WO2008125839; 2008
69. F. Hoffmann-La Roche AG. Quinazoline derivatives as PI3 kinase inhibitors. WO2008152387; 2008
70. F. Hoffmann-La Roche AG. Thiazoliopyrimidines and their use as inhibitors of phosphatidylinositol-3 kinase. WO2008152390; 2008
71. F. Hoffmann-La Roche AG. Pharmaceutical compounds. WO2008152394; 2008
72. Genentech, Inc., F. Hoffmann-La Roche AG. Bicyclic pyrimidine PI3K inhibitor compounds selective for p110 delta, and methods of use. WO2010138589; 2010
73. F. Hoffmann-La Roche AG. Bicyclic Indole-Pyrimidine PI3K inhibitor compounds selective For p110 delta, and methods of use. WO2010136491; 2010
74. F. Hoffmann-La Roche AG. Pyrido[3,2-d]pyrimidine PI3K delta inhibitor compounds and methods of use. WO2011101429; 2011
75. Sweeney ZK. Potent and highly selective benzimidazole inhibitors of PI3-Kinase delta. 242nd ACS National Meeting & Exposition 2011 MEDI15
76. Safina BS. Discovery of potent and highly selective PI3-Kinase Delta inhibitors: Taming time-dependent inhibition. 242nd ACS National Meeting & Exposition 2011 MEDI10
77. Glaxo Group Ltd. 4-Oxadiazol-2-ylindazoles as inhibitors Of PI3 kinases. WO2010102958; 2010
78. Glaxo Group Ltd. Novel compounds. WO2011067364; 2011
79. Glaxo Group Ltd. Benzpyrazole derivatives as PI3-kinase inhibitors. WO2011067365; 2011
80. Glaxo Group Ltd. Indazole derivatives as PI3-kinase inhibitors. WO2011067366; 2011
81. Respivert Ltd. Compounds. WO2011048111; 2011
82. Xcovery Holding Co. LLC PI3K isoform selective inhibitors. WO2010005558; 2010
83. Tyrogenex Inc. PI3K (Delta) selective inhibitors. WO2011041399; 2011
84. Incozen Therapeutics Pvt Ltd. Novel benzopyran kinase modulators. WO2011055215; 2011
85. Viswanadha S, Prasanna R, Muthuppalaniappan M, et al. RP5237- a novel, selective, and potent inhibitor of PI3Kdelta with therapeutic potential in B-cell [abstract 1200]. Lymphomas European Multidisciplinary Cancer Congress; 23 - 27 September 2011; Stockholm
86. Routhu K, Varanasi K, Veeraraghavan S, et al. Pre-clinical efficacy of RP5090 in PI3K delta mediated airway disorders [abstract 4495]. European Respiratory Society Annual Congress; 24 - 28 September 2011; Amsterdam
87. Merck Serono S.A. Tricyclic pyrazolamine derivatives. WO2011058149; 2011
88. Karus Therapeutics Ltd. Tricyclic heterocyclic compounds as phosphoinositide 3-kinase inhibitors. WO2011021038; 2011
89. H. Lundbeck A/S. Diagnosing potential weight gain in a subject. WO2009036768; 2009
90. The United States of America, as Represented by the Secretary, Department of Health and Human Services. Phosphatidylinositol-3-kinase p110 delta-targeted drugs in the treatment of CNS disorders. WO2010065923; 2010