5.04595

Bcr-abl Inhibitor IV, Imatinib

• Synonym(e): Bcr-abl Inhibitor IV, Imatinib, 4-((4-Methyl-1-piperazinyl)methyl)-N-(4-methyl-3-((4-(3-pyridinyl)-2-pyrimidinyl)amino)phenyl)benzamide, Methanesulfonate, STI571, Abl Inhibitor V, PDGFR Tyrosine Kinase Inhibitor XXIV, c-Kit Inhibitor IV, STI571, Abl Inhibitor V, PDGFR Tyrosine Kinase Inhibitor XXIV, c-Kit Inhibitor IV, 4-((4-Methyl-1-piperazinyl)methyl)-N-(4-methyl-3-((4-(3-pyridinyl)-2-pyrimidinyl)amino)phenyl)benzamide, Methanesulfonate
• Empirische Formel (Hill-System): C₂₉H₃₁N₇O · xCH₄O₃S
• CAS-Nummer: 220127-57-1
• Molekulargewicht: 493.60 (free base basis)
• UNSPSC-Code: 12352200
• NACRES: NA.77

Eigenschaften

• Assay: ≥99% (HPLC)
• Qualitätsniveau: 100
• Form: solid
• Hersteller/Markenname: Calbiochem^®
• Lagerbedingungen: OK to freeze; desiccated (hygroscopic); protect from light
• Farbe: white
• Löslichkeit: water: 100 mg/mL
• Lagertemp.: 2-8°C
• InChI: 1S/C29H31N7O.CH4O3S/c1-21-5-10-25(18-27(21)34-29-31-13-11-26(33-29)24-4-3-12-30-19-24)32-28(37)23-8-6-22(7-9-23)20-36-16-14-35(2)15-17-36;1-5(2,3)4/h3-13,18-19H,14-17,20H2,1-2H3,(H,32,37)(H,31,33,34);1H3,(H,2,3,4)
• InChIKey: YLMAHDNUQAMNNX-UHFFFAOYSA-N

Beschreibung

Allgemeine Beschreibung

A cell-permeable, orally bioavailable 2-phenylaminopyrimidine derived compound that competitively binds to ATP-binding site of Abl and stabilizes the inactive conformation, and acts as a highly potent and reversible inhibitor of Abl (IC₅₀ = 38, 25 and 25 nM for v-Abl, Bcr-Abl, and c-Abl, respectively). Also shown to block the activity of PDGFR and c-kit (IC₅₀ = 50 and 100 nM). Exhibits high selectivity over IR, IGF-1R, EGFR, c-Src, JAK-2, PKA, PKC isozymes, CKI, and CKII (IC₅₀ >100 µM). Preferentially blocks the proliferation of leukemic immature cobblestone-forming area cells and Bcr-abl transfected cell lines, M07/p210 and Ba/F3/p185 (~1 -10 µM), and suppresses tumor growth in mice (50 mg/kg, i.p.). Induces apoptosis in Bcr-abl positive cells via intrinsic mitochondrial pathway by down-regulating Bcl-X, promoting cytochrome c release, and activating caspase-9. Does not affect the levels of Bcl-2. Also reported to induce a caspase-independent, necrosis-like programmed cell death mediated by the serine protease activity of Omi/HtrA2.

Biochem./physiol. Wirkung

Cell permeable: yes

Primary Target
Abl

Reversible: yes

Secondary Target
PDGFR, c-kit

Verpackung

Packaged under inert gas

Warnhinweis

Toxicity: Standard Handling (A)

Rekonstituierung

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Sonstige Hinweise

Lin, Y.L., et al. 2013. Proc. Natl. acad. Sci. USA110, 1664.
Okada, M., et al. 2004. Blood103, 2299.
Capdeville, R., et al. 2002. Nat. Rev. Drug. Res.1, 493.
Oetzel, C., et al. 2000. Clin Cancer Res.6, 1958.
Schindler, T., et al. 2000. Science289, 1938.
Buchdunger, E., et al. 2000. J. Pharmacol. Exp. Ther.295, 139.
Carroll. M., et al. 1997. Blood90, 4947.

Zimmermann, J., et al. 1997. Bioorg. Med. Chem. Lett.7, 187.
Druker, B.J., et al. 1996. Nat. Med.2, 561.

Rechtliche Hinweise

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Sicherheitshinweise

• Piktogramme: GHS08
• Signalwort: Warning
• H-Sätze: H361d
• P-Sätze: P201 - P202 - P280 - P308 + P313 - P405 - P501
• Gefahreneinstufungen: Repr. 2
• Lagerklassenschlüssel: 11 - Combustible Solids
• WGK: WGK 3
• Flammpunkt (°F): Not applicable
• Flammpunkt (°C): Not applicable