WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206213
Description: KW-2449 is a novel multikinase inhibitor, which suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Recent research showed that HDACIs increase KW-2449 lethality in Bcr/Abl(+) cells in association with inhibition of Bcr/Abl, generation of ROS, and induction of DNA damage. This strategy preferentially targets primary Bcr/Abl(+) hematopoietic cells and exhibits enhanced in vivo activity. Combining KW-2449 with HDACIs warrants attention in IM-resistant Bcr/Abl(+) leukemias. (source: Clin Cancer Res. 2011 May 15;17(10):3219-32. Epub 2011 Apr 7.).
MedKoo Cat#: 206213
Chemical Formula: C20H20N4O
Exact Mass: 332.16371
Molecular Weight: 332.4
Elemental Analysis: C, 72.27; H, 6.06; N, 16.86; O, 4.81
KW-2449, purity > 98%, is in stock. The same day shipping out after order is received.
Synonym: KW2449; KW-2449; KW 2449.
IUPAC/Chemical Name: (E)-(4-(2-(1H-indazol-3-yl)vinyl)phenyl)(piperazin-1-yl)methanone
InChi Key: YYLKKYCXAOBSRM-JXMROGBWSA-N
InChi Code: InChI=1S/C20H20N4O/c25-20(24-13-11-21-12-14-24)16-8-5-15(6-9-16)7-10-19-17-3-1-2-4-18(17)22-23-19/h1-10,21H,11-14H2,(H,22,23)/b10-7+
SMILES Code: O=C(C1=CC=C(/C=C/C2=NNC3=C2C=CC=C3)C=C1)N4CCNCC4
The following data is based on the product molecular weight 332.4 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
1. Pratz, Keith W.; Sato, Takashi; Murphy, Kathleen M.; Stine, Adam; Rajkhowa, Trivikram; Levis, Mark. FLT3-mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML. Blood (2010), 115(7), 1425-1432. CODEN: BLOOAW ISSN:0006-4971. AN 2010:301893
2. Shiotsu, Yukimasa; Kiyoi, Hitoshi; Akinaga, Shiro; Naoe, Tomoki. Screening of molecular target therapy of cancer and generation of new kinase inhibitor, KW-2449. Saibo (2009), 41(9), 381-384. CODEN: SAIBC7 ISSN:1346-7557. AN 2009:1319160
3. Verma, Dushyant; Kantarjian, Hagop M.; Jones, Dan; Luthra, Rajyalakshmi; Borthakur, Gautam; Verstovsek, Srdan; Rios, Mary Beth; Cortes, Jorge. Chronic myeloid leukemia (CML) with P190BCR-ABL: analysis of characteristics, outcomes, and prognostic significance. Blood (2009), 114(11), 2232-2235. CODEN: BLOOAW ISSN:0006-4971. CAN 152:188988 AN 2009:1173490
4. Shiotsu, Yukimasa; Kiyoi, Hitoshi; Ishikawa, Yuichi; Tanizaki, Ryohei; Shimizu, Makiko; Umehara, Hiroshi; Ishii, Kenichi; Mori, Yumiko; Ozeki, Kazutaka; Minami, Yosuke; Abe, Akihiro; Maeda, Hiroshi; Akiyama, Tadakazu; Kanda, Yutaka; Sato, Yuko; Akinaga, Shiro; Naoe, Tomoki. KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood (2009), 114(8), 1607-1617. CODEN: BLOOAW ISSN:0006-4971. CAN 151:462381 AN 2009:1081843
5. Pratz, Keith W.; Cortes, Jorge; Roboz, Gail J.; Rao, Niranjan; Arowojolu, Omotayo; Stine, Adam; Shiotsu, Yukimasa; Shudo, Aiko; Akinaga, Shiro; Small, Donald; Karp, Judith E.; Levis, Mark. A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response. Blood (2009), 113(17), 3938-3946. CODEN: BLOOAW ISSN:0006-4971. CAN 152:701 AN 2009:541826
6. Tomillero A; Moral M A Gateways to clinical trials. Methods and findings in experimental and clinical pharmacology (2009), 31(1), 47-57. Journal code: 7909595. ISSN:0379-0355. PubMed ID 19357798 AN 2009268576
7. Shiotsu Yukimasa New therapeutic option for leukemia patients, with FLT3/Aurora kinase inhibitor, KW-2449: strategy and comparison with other kinase inhibitors. [Rinsho ketsueki] The Japanese journal of clinical hematology (2008), 49(8), 641-9. Journal code: 2984782R. ISSN:0485-1439. PubMed ID 18800614 AN 2008612636
8. Bayes M; Rabasseda X Gateways to clinical trials. Methods and findings in experimental and clinical pharmacology (2008), 30(1), 67-99. Journal code: 7909595. ISSN:0379-0355. PubMed ID 18389098 AN 2008229509
KW-2449, a multikinase inhibitor of FLT3, ABL, ABL-T315I, and Aurora kinase, is under investigation to treat leukemia patients. KW-2449 showed the potent growth inhibitory effects on leukemia cells with FLT3 mutations by inhibition of the FLT3 kinase, resulting in the down-regulation of phosphorylated-FLT3/STAT5, G1 arrest, and apoptosis. Oral administration of KW-2449 showed dose-dependent and significant tumor growth inhibition in FLT3-mutated xenograft model with min. bone marrow suppression. In FLT3 wild-type human leukemia, it induced the redn. of phosphorylated histone H3, G2/M arrest, and apoptosis. In imatinib-resistant leukemia, KW-2449 contributed to release of the resistance by the simultaneous down-regulation of BCR/ABL and Aurora kinases. Furthermore, the antiproliferative activity of KW-2449 was confirmed in primary samples from AML and imatinib-resistant patients. The inhibitory activity of KW-2449 is not affected by the presence of human plasma protein, such as .alpha.1-acid glycoprotein. These results indicate KW-2449 has potent growth inhibitory activity against various types of leukemia by several mechanisms of action. KW-2449 has significant activity and warrants clin. study in leukemia patients with FLT3 mutations as well as imatinib-resistant mutations. See: Shiotsu, Yukimasa; Kiyoi, Hitoshi; Ishikawa, Yuichi; Tanizaki, Ryohei; Shimizu, Makiko; Umehara, Hiroshi; Ishii, Kenichi; Mori, Yumiko; Ozeki, Kazutaka; Minami, Yosuke; Abe, Akihiro; Maeda, Hiroshi; Akiyama, Tadakazu; Kanda, Yutaka; Sato, Yuko; Akinaga, Shiro; Naoe, Tomoki. Fuji Research Park, Kyowa Hakko Kirin, Shizuoka, Japan. Blood (2009), 114(8), 1607-1617.