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Imatinib and its successors--how modern chemistry has changed drug development


, : Imatinib and its successors--how modern chemistry has changed drug development. Current Pharmaceutical Design 15(2): 120-133

Since protein kinases are frequently mutated or otherwise deregulated in human malignancies, they serve as a target for differentiating between tumor cells and normal tissues. Imatinib mesylat (IM), an inhibitor of the BCR-ABL tyrosine kinase was introduced in 2001 and has revolutionized the treatment of patients with chronic myeloid leukemia (CML). Since 2005 a second generation of tyrosine kinase inhibitors is to follow in Imatinib's footsteps: The development of these new small molecules was promoted by the identification of potential target kinases within the cellular signaling apparatus. Modern biochemical tools provide relevant amounts of these target kinases necessary for high throughput screening (HTS) campaigns and for elucidation of their 3-D structure by crystallography. Supported by computational chemistry the resulting data have enabled rational drug design. In this review low molecular weight inhibitors used for the CML treatment are summarized, pointing out their chemical similarities and differences.

US$29.90

PMID: 19149608


Other references

Sowers, M.; Derby, C.; Jannausch, M.L.; Torrens, J.I.; Pasternak, R., 2003: Insulin resistance, hemostatic factors, and hormone interactions in pre- and perimenopausal women: SWAN. We evaluated the association of hemostatic factors with insulin resistance in relation to reproductive hormones including FSH, estradiol, testosterone, and SHBG. SHBG was used to calculate the free estradiol index and free androgen index. We studi...

Yang, M.; Cai, L.; Tai, Z.; Zeng, X.; Ding, Z., 2011: Four new phenanthrenes from Monomeria barbata Lindl. Three biphenanthrene compounds (1-3) and a triphenanthrene compound (4), together with six known biphenanthrene compounds (5-10), were isolated from the tubers of Monomeria barbata Lindl. Their structures were elucidated on the basis of extensive...

Grajek W., 1988: Cooling aspects of solid state cultures of mesophilic and thermophilic fungi. Cooling air requirements in solid-state cultures of filamentous fungi were studied. The growth conditions of Trichoderma viride TS, Thermoascus aurantiacus and Sporotrichum (Chrysosporium) thermophile in sugar-beet pulp medium were estimated. Heat...

Lee, B.K.ung; Jung, Y.S.ok; Jeong, E.M.oung; Park, S.L.ea; Lee, S.H.an; Baik, E.J.o; Moon, C.K.u; Moon, C.H.un, 2004: Cadmium induces apoptosis through PI3K MAPK-dependent pathway in human T cells. Cadmium (Cd), an ubiquitous heavy metal, has been known to damage the immune system including T lymphocytes, although their mechanism was not fully elucidated. In the present study, we tried to investigate the signaling pathways involved in the Cd...

Chandross, K.J.; Mezey, E.; Guzik, A.; Mckercher, S.; Maki, R.; Hudson, L.D., 2001: Adult mammalian bone marrow gives rise to cells that express neural antigens. Journal of Neurochemistry 78(Supplement 1): 6, September

Bauer, A.W.; Perry, D.M.; Kirby, W.M., 1959: Single-disk antibiotic-sensitivity testing of staphylococci; an analysis of technique and results. A.M.A. Archives of Internal Medicine 104(2): 208-216

Jay, V.; Becker, L.E.; Otsubo, H.; Cortez, M.; Hwang, P.; Hoffman, H.J.; Zielenska, M., 1994: Chronic encephalitis and epilepsy CMV and HSV1 positivity by polymerase chain reaction and in situ hybridization. Neurology 44(4 SUPPL 2): A138

Oreto, G.; Satullo, G.; Luzza, F.; Arrigo, F., 1984: Modulated parasystole. An arrhythmia waiting for diagnostic criteria. Deductive analysis of a case. We report a case of ventricular parasystole in which the long interectopic intervals are always less than a multiple of the short interectopic intervals. Assuming a regular ectopic discharge, the above said phenomenon could theoretically be due to...

Joswick, H.L.; Corner, T.R.; Silvernale, J.N.; Gerhardt, P., 1971: Antimicrobial actions of hexachlorophene: release of cytoplasmic materials. Intracellular solutes were released from growing or resting cells of Bacillus megaterium as a consequence of hexachlorophene treatment. The effect was dose dependent, with the optimum at a concentration about sevenfold greater than the minimal let...

Young, S.N.; St-Arnaud-Mckenzie, D.; Sourkes, T.L., 1978: Importance of tryptophan pyrrolase and aromatic amino acid decarboxylase in the catabolism of tryptophan. Benserazide, an inhibitor of aromatic amino acid decarboxylase, potentiates the rise of plasma tryptophan in rats given a tryptophan load. It also inhibits 14CO2 release from animals given carboxyl-labeled tryptophan. These results are explained b...