{4-[(E)-2-(1H-Indazol-3-yl)vinyl]phenyl}(1-piperazinyl)methanone
(E)-(4-(2-(1H-indazol-3-yl)vinyl)phenyl)(piperazin-1-yl)methanone
CAS: 1000669-72-6
Molecular Formula: C20H20N4O
{4-[(E)-2-(1H-Indazol-3-yl)vinyl]phenyl}(1-piperazinyl)methanone - Names and Identifiers
{4-[(E)-2-(1H-Indazol-3-yl)vinyl]phenyl}(1-piperazinyl)methanone - Physico-chemical Properties
| Molecular Formula | C20H20N4O |
| Molar Mass | 332.4 |
| Density | 1.28 |
| Boling Point | 604.1±55.0 °C(Predicted) |
| Solubility | DMSO : 50 mg/mL mother liquor preservation: sub-package and freeze storage to avoid repeated freezing and thawing;-20 ℃,1 month;-80 ℃,6 months (after dilution, the solution temperature is low and storage may precipitate, try to use it now) Cell experiment: Dissolve with DMSO first: dilute with culture medium then, and the dilution process is recommended to be carried out in stages to avoid too fast concentration change leading to compound precipitation. If the compound is precipitated during the dilution process, it can be redissolved by ultrasound. During dilution, ensure that the final concentration of DMSO in the working fluid should be below 0.1% as far as possible, and the maximum should not exceed 0.5%, and set up a DMSO control group with corresponding concentration. Animal experiment: Dissolve with DMSO first: dilute with water or normal saline, etc. The dilution process is recommended to be carried out in sections to avoid excessive concentration changes leading to compound p |
| Appearance | solid |
| Color | Pale yellow |
| pKa | 13.76±0.40(Predicted) |
| Storage Condition | -20°C |
| Stability | Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month. |
| Use | 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.). IC50 values for FLT3,ABL,ABLT315I and Aurora kinase were 6.6,14,4 and 48 nM, respectively. |
| Target | Abl；ABL-T315I;FGFR1;Aurora A;FLT3/D835Y;FLT3;JAK2;SRC;PDFGRα |
| In vitro study | KW-2449 is a multikinase inhibitor of FLT3, ABL, ABL-T315I, and Aurora kinases for the treatment of leukemia patients. KW-2449 acts on leukemic cells carrying the FLT3 mutation, effectively inhibiting growth by inhibiting FLT3 kinase, resulting in down-regulation of phosphorylated-FLT3/STAT5, cell cycle arrest at G1 phase, and apoptosis. KW-2449 Oral treatment of FLT3 mutant xenograft model significantly inhibited tumor growth with the lowest rate of bone marrow suppression. KW-2449 acts on FLT3 wild-type human leukemia, inducing a decrease in phosphorylated histone H3, cell cycle arrest at G2/M, and apoptosis. KW-2449 acts on Imatinib-resistant leukemias, releasing resistance by simultaneously down-regulating BCR/ABL and Aurora kinases. Human plasma proteins, such as α1-acid glycoprotein, do not affect the inhibitory activity of KW-2449. KW-2449 acts on various types of leukemia and effectively inhibits growth. KW-2449 has significant activity in leukemia patients with FLT3 mutations and anti-Imatinib mutations, and clinical studies are warranted. KW-2449 reduced phosphorylation of FLT3 and STAT5 in a dose-dependent manner. In addition, KW-2449 effectively inhibit ABL-T315I, IC50 is 4 nM. On the other hand, KW-2449 had no effect on PDGFR β, IGF-1R, EGFR, and various serine/threonine kinases even at a concentration of 1 μm. Both FLT3/ITD expressing leukemia cells and FLT3/KDM activated and wild-type FLT3 overexpressing leukemia cells were effectively inhibited by KW-2449. Consistent with inhibition of growth, KW-2449 acts on MOLM-13 cells in a dose-dependent manner to inhibit the phosphorylation of FLT3 (P-FLT3) and its downstream molecule, phospho-stat5 (P-STAT5). Moreover, KW-2449 increased the percentage of G1 phase, while decreasing the percentage of S phase led to an increase in the number of apoptotic cells. KW-2449 can dephosphorylate constitutively activated WT-FLT3 kinases without inhibiting leukemic cell proliferation. KW-2449 is rapidly absorbed and converted to a major metabolite, M1. Preclinical studies have shown that monoamine oxidase-B(MAO-B) and aldehyde oxidase convert KW-2449 to its major metabolite, M1. KW-2449 regulates cytotoxicity by inhibiting FLT3/ITD. KW-2449 is a FLT3 inhibitor that induces inhibition of the downstream target, STAT5. KW2449 synergizes with HDACIs to act on Ph |
| In vivo study | KW-2449 oral treatment of MOLM-13 transplanted tumor model, treatment for 14 days, has a significant anti-cancer effect, this effect is dose-dependent. |
{4-[(E)-2-(1H-Indazol-3-yl)vinyl]phenyl}(1-piperazinyl)methanone - Reference
| Reference Show more | 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 2010:3018932. 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 2009:13191603. 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 2009:11734904. 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 2009:10818435. Pratz, Keith W.; Cortes, Jorge; Roboz, Gail J.; Rao, Niranjan; Arowojolu, Omotayo; Stine, Adam; Shiotsu, Yukimasa; S |
{4-[(E)-2-(1H-Indazol-3-yl)vinyl]phenyl}(1-piperazinyl)methanone - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 3.008 ml | 15.042 ml | 30.084 ml |
| 5 mM | 0.602 ml | 3.008 ml | 6.017 ml |
| 10 mM | 0.301 ml | 1.504 ml | 3.008 ml |
| 5 mM | 0.06 ml | 0.301 ml | 0.602 ml |
Last Update：2024-01-02 23:10:35
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Product Name: (E)-(4-(2-(1H-indazol-3-yl)vinyl)phenyl)(piperazin-1-yl)methanone Visit Supplier Webpage Request for quotationCAS: 1000669-72-6
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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