Recent advances in the design and discovery of small-molecule therapeutics targeting HER2/neu

Expert Opinion on Therapeutic Patents

Volumn 17, Issue 1, 2007, Pages 83-102

  Dayam, Raveendra ^a   Grande, Fedora ^a   Al Mawsawi, Laith Q ^a   Neamati, Nouri ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

Anticancer drug; HER2; Monoclonal antibody; Small molecule; Tyrosine kinase inhibitor

Indexed keywords

6 (4 HYDROXYPHENYL) 4 (ALPHA METHYLBENZYLAMINO) 7H PYRROLO[2,3 D]PYRIMIDINE; BMS 599626; CANERTINIB; CETUXIMAB; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE; ERLOTINIB; GEFITINIB; GEMCITABINE; ILOMASTAT; LAPATINIB; MATRIX METALLOPROTEINASE; OXAZOLE DERIVATIVE; PANITUMUMAB; PERTUZUMAB; PROTEIN TYROSINE KINASE INHIBITOR; PYRIDAZINE DERIVATIVE; PYRROLE DERIVATIVE; PYRROLOPYRIMIDINE DERIVATIVE; QUINAZOLINE DERIVATIVE; TAK 165; THIAZOLE DERIVATIVE; TRANSCRIPTION FACTOR ETS; TRASTUZUMAB; TRIAZINE DERIVATIVE; UNCLASSIFIED DRUG;

ADJUVANT THERAPY; ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; BLADDER CANCER; BREAST CANCER; CANCER CELL CULTURE; CANCER SURVIVAL; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; CYTOSTASIS; CYTOTOXICITY; DIARRHEA; DIMERIZATION; DRUG ABSORPTION; DRUG ACCUMULATION; DRUG APPROVAL; DRUG DESIGN; DRUG POTENTIATION; DRUG RESEARCH; DRUG STRUCTURE; DRUG TARGETING; ENZYME INHIBITION; FOOD AND DRUG ADMINISTRATION; GENE OVEREXPRESSION; HUMAN; INHIBITION KINETICS; KIDNEY CANCER; LUNG CARCINOMA; MALIGNANT NEOPLASTIC DISEASE; MONOTHERAPY; NAUSEA AND VOMITING; NONHUMAN; PANCREAS CARCINOMA; PATENT; PROSTATE CANCER; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN PHOSPHORYLATION; RASH; REVIEW; SIDE EFFECT; TUMOR VOLUME;

EID: 33846179026     PISSN: 13543776     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543776.17.1.83     Document Type: Review

References (62)

1. SCHLESSINGER J: Cell signaling by receptor tyrosine kinases. Cell (2000) 103(2):211-225.
2. WELLS A. EGF receptor. Int. J. Biochem. Cell Biol. (1999) 31(6):637-643.
3. GUY PM, PLATKO JV, CANTLEY LC, CERIONE RA, CARRAWAY KL III: Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase activity. Proc. Natl. Acad. Sci. USA (1994) 91(17):8132-8136.
4. JONES JT, AKITA RW, SLIWKOWSKI MX: Binding specificities and affinities of egf domains for ErbB receptors. FEBS Lett. (1999) 447(2-3):227-231.
5. GULLICK WJ: The type 1 growth factor receptors and their ligands considered as a complex system. Endocr. Relat. Cancer (2001) 8(2):75-82.
6. CHO HS, MASON K, RAMYAR KX et al: Structure of the extracellular region of HER2 alone and in complex with the herceptin Fab. Nature (2003) 421(6924):756-760.
7. GARRETT TP, MCKERN NM, LOU M et al: The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors. Mol. Cell (2003) 11(2):495-505.
8. ALIMANDI M, ROMANO A, CURIA MC et al: Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene (1995) 10(9):1813-1821.
9. BLENIS J: Signal transduction via the MAP kinases: proceed at your own RSK. Proc. Natl. Acad. Sci. USA (1993) 90(13):5889-5892.
10. BURGERING BM, COFFER PJ: Protein kinase B (c-Akt) in phosphatidylinosicol-3-OH kinase signal transduction. Nature (1995) 376(6541):599-602.
11. OLAYIOYE MA, NEVE RM, LANE HA, HYNES NE: The ErbB signaling network: receptor heterodimerization in development and cancer. Embo. J. (2000) 19(13):3159-3167.
12. ZHANG W, LIU HT. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res. (2002) 12(1):9-18.
13. CANTLEY LC: The phosphoinositide 3-kinase pathway. Science (2002) 296(5573):1655-1657.
14. MOSCATELLO DK, HOLGADO-MADRUGA M, EMLET DR, MONTGOMERY RB, WONG AJ: Constitutive activation of phosphatidylinositol 3-kinase by a naturally occurring mutant epidermal growth factor receptor. J. Biol. Chem. (1998) 273(1):200-206.
15. HYNES NE, LANE HA: ERBB receptors and cancer: the complexity of targeted inhibitors. Nat. Rev. Cancer (2005) 5(5):341-354.
16. SLAMON DJ, CLARK GM, WONG SG et al: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science (1987) 235(4785):177-182.
17. SLAMON DJ, GODOLPHIN W, JONES LA et al: Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science (1989) 244(4905):707-712.
18. KAPITANOVIC S, RADOSEVIC S, KAPITANOVIC M et al: The expression of p185(HER-2/neu) correlates with the stage of disease and survival in colorectal cancer. Gastroenterology (1997) 112(4):1103-1113.
19. NAHTA R, ESTEVA FJ: HER-2-targeted therapy: lessons learned and future directions. Clin. Cancer Res. (2003) 9(14):5078-5084.
20. SLIWKOWSKI MX, LOFGREN JA, LEWIS GD et al: Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin. Oncol. (1999) 26(4 Suppl. 12):60-70.
21. DREBIN JA, LINK VC, STERN DF, WEINBERG RA, GREENE MI: Down-modulation of an oncogene protein product and reversion of the transformed phenotype by mAbs. Cell (1985) 41(3):697-706.
22. IZUMI Y, XU L, DI TOMASO E, FUKUMURA D, JAIN RK: Turnout biology: herceptin acts as an anti-angiogenic cocktail. Nature (2002) 416(6878):279-280.
23. PICCART-GEBHART MJ, PROCTER M, LEYLAND-JONES B et al: Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N. Engl. J. Med. (2005) 353(16):1659-1672.
24. AGUS DB, AKITA RW, FOX WD et al: Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell (2002) 2(2):127-137.
25. FRANKLIN MC, CAREY KD, VAJDOS FF et al: Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell (2004) 5(4):317-328.
26. RABINDRAN SK- Antitumor activity of HER-2 inhibitors. Cancer Lett. (2005) 227(1):9-23.
27. MOULDER SL, YAKES FM, MUTHUSWAMY SK et at: Epidermal growth factor receptor (HERI) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/ neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo. Cancer Res. (2001) 61(24):8887-8895.
28. MOASSER MM, BASSO A, AVERBUCH SD, ROSEN N: The tyrosine kinase inhibitor ZD1839 ("Iressa") inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. Cancer Res. (2001) 61(19):7184-7188.
29. ANDERSON NG, AHMAD T, CHAN K, DOBSON R, BUNDRED NJ: ZD1839 (Iressa), a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, potently inhibits the growth of EGFR-positivc cancer cell lines with or without ErbB2 overexpression. Int. J. Cancer (2001) 94(6):774-782.
30. ARORA A, SCHOLAR EM: Role of tyrosine kinase inhibitors in cancer therapy. J. Pharmacol. Exp. Ther. (2005) 315(3):971-979.
31. XIA W, MULLIN RJ, KEITH BR et al: Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/ErbB2 and downstream Erk 1/2 and AKT pathways. Oncogene (2002) 21(41):6255-6263.
32. RUSNAK DW, LACKEY K, AFFLECK K et al: The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol. Cancer Ther. (2001) 1(2):85-94.
33. BENCE AK, ANDERSON EB, HALEPOTA MA et al.: Phase I pharmacokinetic studies evaluating single and multiple doses of oral GW572016, a dual EGFR-ErbB2 inhibitor, in healthy subjects. Invest. New Drugs (2005) 23(1):39-49.
34. XIA W, LIU LH, HO P, SPECTOR NL: Truncated ErbB2 receptor (p95ErbB2) is regulated by heregulin through heterodimer formation with ErbB3 yet remains sensitive to the dual EGFR/ErbB2 kinase inhibitor GW572016. Oncogene (2004) 23(3):646-653.
35. KONECNY GE, PEGRAM MD, VENKATESAN N et al: Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-over-expressing and trastuzumab-treated breast cancer cells. Cancer Res. (2006) 66(3):1630-1639.
36. XIA W, GERARD CM, LIU L et al: Combining lapatinib (GW572016), a small molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases, with therapeutic anti-ErbB2 antibodies enhances apoptosis of ErbB2-overexpressing breast cancer cells. Oncogene (2005) 24(41):6213-6221.
37. GEYER CE, CAMERON D, LINDQUIST D et al.: A Phase III randomized, open-label, international study comparing laparinib and capecitabine vs capacitabine in women with refractory advanced or metastatic breast cancer (EGF100151). 2006 American Society of Clinical Oncology Annual Meeting. Atlanta, Georgia (2006).
38. SMAILL JB, PALMER BD, REWCASTLE GW et al: Tyrosine kinase inhibitors. 15. 4-(Phenylamino)quinazoline and 4-(phenylamino)pyrido[d]pyrimidine acrylamides as irreversible inhibitors of the ATP binding site of the epidermal growth factor receptor. J. Med. Chem. (1999) 42(10):1803-1815.
39. FRY DW, BRIDGES AJ, DENNY WA et al.: Specific, irreversible inactivation of the epidermal growth factor receptor and ErbB2, by a new class of tyrosine kinase inhibitor. Proc. Natl. Acad Sci. USA (1998) 95(20):12022-12027.
40. SIMON GR, GARRETT CR, OLSON SC et al.: Increased bioavailability of intravenous versus oral CI-1033, a pan erbB tyrosine kinase inhibitor: results of a Phase I pharmacokinetic study. Clin. Cancer Res. (2006) 12(15):4645-4651.
41. GARLAND LL, HIDALGO M, MENDELSON DS et al: A Phase I clinical and pharmacokineric study of oral CI-1033 in combination with docetaxel in patients with advanced solid tumors. Clin. Cancer Res. (2006) 12(4 Pt 1):4274-4282.
42. MOMOSE Y, MAEKAWA T, ODAKA H, IKEDA H, SOHDA T: Novel 5-substituted-1 H-retrazole derivatives as potent glucose and lipid lowering agents. Chem. Pharm. Bull. (Tokyo) (2002) 50(1):100-111.
43. MOMOSE Y, MAEKAWA T, YAMANO T et al: Novel 5-substituted 2,4-thiazolidinedione and 2,4-oxazolidinedione derivatives as insulin sensitizers with antidiabetic activities. J. Med. Chem. (2002) 45(7):1518-1534.
44. SRIDHAR SS, SEYMOUR L, SHEPHERD FA. Inhibitors of epidermal-growth-factor receptors: a review of clinical research with a focus on non-small-cell lung cancer. Lancet Oncol. (2003) 4(7):397-406.
45. NAGASAWAJ, MIZOKAMI A, KOSHIDA K et al: Novel HER2 selective tyrosine kinase inhibitor, TAK-165, inhibits bladder, kidney and androgen-independent prostate cancer in vitro and in vivo. Int. J. Urol. (2006) 13(5):587-592.
46. GUNDERSEN LL, MALTERUD KE, NEGUSSIE AH et al: Indolizines as novel potent inhibitors of 15-lipoxygenase. Bioorg. Med. Chem. (2003) 11(24):5409-5415.
47. CHEN Z, KIM SH, BARBOSA SA et al.: Pyrrolopyridazine MEK inhibitors. Bioorg. Med. Chem. Lett (2006) 16(3):628-632.
48. HUNT JT, MITT T, BORZILLERI R et al: Discovery of the pyrrolo[2,1-f] [1,2,4] triazine nucleus as a new kinase inhibitor template. J. Med. Chem. (2004) 47(16):4054-4059.
49. FINK BE, VITE GD, MASTALERZ H et al: New dual inhibitors of EGFR and HER2 protein tyrosine kinases. Bioorg, Med. Chem. Lett (2005) 15(21):4774-4779
50. WONG TW, LEE FY, YU C et al.: Preclinical antitumor activity of BMS-599626, a pan-HER kinase inhibitor that inhibits HER1/HER2 homodimer and heterodimer signaling. Clin. Cancer Res. (2006) 12(20 Pt 1):6186-6193.
51. BORZILLERI RM, ZHENG X, QIAN L et al: Design, synthesis and evaluation of orally active 4-(2,4-difluoro-5-(methoxy-carbamoyl)phenylamino)pyrrolo[2,1-f] [1,2,4]triazines as dual vascular endothelial growth factor reccptor-2 and fibroblast growth factor receptor-1 inhibitors. J. Med. Chem. (2005) 48(12):3991-4008.
52. BORZILLERI RM, CAI ZW, ELLIS C et al: Synthesis and SAR of 4-(3-hydroxy-phenylamino)pyrrolo[2,1-f][1,2,4]triazine based VEGFR-2 kinase inhibitors. Bioorg. Med. Chem. Lett. (2005) 15(5):1429-1433.
53. TRAXLER PM, FURET P, METT H et al.: 4-(Phenylamino)pyrrolopyrimidines: potent and selective, ATP site directed inhibitors of the EGF-receptor protein cyrosine kinase. J. Med. Chem. (1996) 39(12):2285-2292.
54. TRAXLER P, BOLD G, BUCHDUNGER E et al.: Tyrosine kinase inhibitors: from rational design to clinical trials. Med. Res. Rev. (2001) 21(6):499-512.
55. HOEKSTRA R, DUMEZ H, ESKENS FA et al.: Phase I and pharmacologic study of PKI166, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. Clin. Cancer Res. (2005) 11(19 Pt 1):6908-6915.
56. MELLINGHOFF IK, TRAN C, SAWYERS CL: Growth inhibitory effects of the dual ErbB1/ErbB2 tyrosine kinase inhibitor PKI-166 on human prostate cancer xenografts. Cancer Res. (2002) 62(18):5254-5259.
57. CHANG CH, SCOTT GK, KUO WL et al.: ESX: a structurally unique Ets overexpressed early during human breast tumorigenesis. Oncogene (1997) 14(13):1617-1622.
58. LIN YZ, CLINTON GM: A soluble protein related to the HER-2 proto-oncogene product is released from human breast carcinoma cells. Oncogene (1991) 6(4):639-643.
59. PUPA SM, MENARD S, MORELLI D et al.: The extracellular domain of the c-erbB-2 oncoprotein is released from tumor cells by proteolytic cleavage. Oncogene (1993) 8(11):2917-2923.
60. KANDL H, SEYMOUR L, BEZWODAW R: Soluble c-erbB-2 fragment in serum correlates with disease stage and predicts for shortened survival in patients with early-stage and advanced breast cancer. Br. J. Cancer (1994) 70(4):739-742.
61. SAEZ R, MOLINA MA, RAMSEY EE et al.: p95HER-2 predicts worse outcome in patients with HER-2-positive breast cancer. Clin. Cancer Res. (2006) 12(2):424-431.
62. KERKELA R, GRAZETTE L, YACOBI R et al.: Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat. Med. (2006) 12(8):908-916.