KW-2449|cas 1000669-72-6|DC Chemicals

Cas No.:	841259-17-4
Chemical Name:	(E)-(4-(2-(1H-Indazol-3-yl)vinyl)phenyl)(piperazin-1-yl)methanone
Synonyms:	METHANONE, [4-[(1E)-2-(1H-INDAZOL-3-YL)ETHENYL]PHENYL]-1-PIPERAZINYL-, HYDROCHLORIDE (1:2);KW 2449;KW2449;2D9N67F58G;(E)-(4-(2-(1H-indazol-3-yl)vinyl)phenyl)(piperazin-1-yl)methanone;Methanone, (4-(2-(1H-indazol-3-yl)ethenyl)phenyl)-1-piperazinyl-;Methanone, [4-[2-(1H-indazol-3-yl)ethenyl]phenyl]-1-piperazinyl-;(E)-(4-(2-(1H-Indazol-3-yl)vinyl)-phenyl)(piperazin-1-yl)methanone;YYLKKYCXAOBSRM-JXMROGBWSA-N;(E)-(4-(2-(1H-Indazol-3-yl)vinyl)phenyl)(piperazin-1-yl)methanone hydrochloride;MLS006011;[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone;MLS006011271;GT
SMILES:	O=C(C1C=CC(/C=C/C2C3=CC=CC=C3NN=2)=CC=1)N1CCNCC1
Formula:	C₂₀H₂₀N₄O
M.Wt:	332.3990
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:

KW 2449 is a multikinase inhibitor of FLT3, ABL, ABL-T315I, and Aurora kinase. KW 2449 displays potent inhibition of growth effects on leukemia cells with FLT3 mutations via inhibition of the FLT3 kinase, resulting in the down-regulation of phosphorylated-FLT3/STAT5, G1 arrest, and apoptosis. KW 2449 induces the reduction of phosphorylated histone H3, G2/M arrest, and apoptosis in FLT3 wild-type human leukemia. KW 2449 contributes to release of the resistance by the simultaneous down-regulation of BCR/ABL and Aurora kinases in imatinib-resistant leukemia. KW 2449 inhibitory activity is not affected by the presence of human plasma protein, such as α1-acid glycoprotein. KW 2449 has potent growth inhibitory activity against various types of leukemia by several mechanisms of action. KW 2449 decreases phosphorylation levels of FLT3 and STAT5 in a dose-dependent manner. KW 2449 is a potent inhibitor of ABL-T315I, which is associated with IM resistance (IC50 of 4 nM). KW-2449 has the potent growth inhibitory activities against not only FLT3/ITD-expressing leukemia cells but also FLT3/KDM-activated and wild-type FLT3-overexpressing leukemia cells. KW 2449 suppresses the phosphorylations of FLT3 (P-FLT3) and its downstream molecule phospho-STAT5 (P-STAT5) in MOLM-13 cells in a dose-dependent manner. KW 2449 can dephosphorylate constitutively active WT-FLT3 kinase but not inhibit the proliferation of leukemia cells if they are not mainly addicted to FLT3 the kinase. KW 2449 mediates cytotoxicity through inhibition of FLT3/ITD. KW 2449 is a direct inhibitor of FLT3 and induces inhibition of its downstream target STAT5. KW 2449 interacts synergistically with HDACIs to induce apoptosis in Ph+ CML cells in a time- and concentration-dependent manner. KW 2449 moderately reduces phosphorylation of histone H3, an indicator of Aurora B activity, in nocodozole-treated K562 cells.

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KW-2449 Hydrochloride