Quizartinib

SKU: orb1306579

特色

描述

Quizartinib (AC220) is a potent and selective oral type II FLT3 inhibitor, effective against both FLT3-WT and FLT3-ITD mutations. It induces apoptosis in leukemic cells and has demonstrated significant anti-tumor activity in preclinical models of acute myeloid leukemia (AML), supporting its investigation in both in vitro and in vivo research.

研究领域

Cardiovascular Research, Cell Biology, Pharmacology & Drug Discovery, Signal Transduction

图片与验证

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关键属性

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CAS 号	950769-58-1
MW	560.67
纯度	>98%
分子式	C₂₉H₃₂N₆O₄S
SMILES	CC(C)(C)c1cc(NC(=O)Nc2ccc(cc2)-c2cn3c(n2)sc2cc(OCCN4CCOCC4)ccc32)no1
靶点	Kinase
溶解性	Soluble in DMSO (up to at least 25 mg/ml)

生物活性

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靶点 IC50	FLT3:1.6 nM (Kd, cell free)
体内	Treatment with AC220 at 10 mg/kg resulted in rapid and complete regression of tumors in all animals, and no tumor regrowth was observed during the 60-day posttreatment observation period. AC220 prolonged survival in a dose-dependent manner. At 10 mg/kg, 80% of animals treated survived until the study was terminated on day 172, 119 days after discontinuation of treatment, corresponding to at least a 250% increase in life span (ILS). At the time the study was terminated the animals did not exhibit any signs of disease. At 1 mg/kg a significant increase in the mean survival time was observed, to 77 days. At the lowest dose tested of 0.1 mg/kg, a marginal 10% ILS relative to vehicle was observed . At 1 mg/kg of AC220, tumor growth was completely inhibited during the dosing period, after which growth resumed. At 3 and 10 mg/kg of AC220, tumors regressed almost completely and the tumor volume stayed suppressed after dosing was halted. At 3 mg/kg, tumors appeared to regrow after day 49 (21 days post last dose), while there was no sign of tumor regrowth until day 60 (32 days post last dose) in the animals treated with 10 mg/kg of AC220 .
体外	The highest affinity target identified for Quizartinib (AC220) was FLT3. The only other kinases with binding constants within 10-fold that for FLT3 were the closely related receptor tyrosine kinases (RTKs) KIT, PDGFRA, PDGFRB, RET, and CSF1R, and only 4 additional kinases, also related RTKs (FLT1, FLT4, DDR1, VEGFR2), bound with Kds within 100-fold of that for FLT3. In primary cells, treatment with AC220 for 1 hour inhibited FLT3 autophosphorylation (IC50: 2 nM), comparable with the activity observed in the MV4-11 cell line. The primary cells were sensitive to AC220 (IC50: 0.3 nM), again comparable with the activity observed in the MV4-11 cell line . It inhibits the proliferation of the human leukemia cell line MV4-11, which harbors a homozygous FLT3-ITD mutation, with an IC50 value of 0.56 nM .
细胞研究	MV4-11 and RS4;11 cells were cultured in Iscove media with 10% fetal bovine serum (FBS) and RPMI complete with 10% FBS, respectively. For proliferation assays, cells were cultured overnight in low serum media (0.5% FBS), then seeded in a 96-well plate at 40 000 cells per well. Inhibitors were added to the cells and incubated at 37°C for 72 hours. Cell viability was measured using the Cell Titer-Blue Cell Viability Assay. To measure inhibition of FLT3 autophosphorylation, cells were cultured in low serum media (0.5% FBS) overnight and seeded at a density of 400 000 cells per well in a 96-well plate the following day. The cells were incubated with inhibitors for 2 hours at 37°C. To induce FLT3 autophosphorylation in RS4;11 cells, 100 ng/mL FLT3 ligand was added for 15 minutes after the 2-hour compound incubation. Cell lysates were prepared and incubated in 96-well plates pre-coated with a total FLT3 capture antibody. The coated plates were incubated with either a biotinylated antibody against FLT3 to detect total FLT3 or an antibody against phosphotyrosines to detect FLT3 autophosphorylation. In both cases, a SULFO-tagged streptavidin secondary antibody was used for electrochemiluminescence detection on the Meso Scale Discovery platform .
动物研究	The model was performed according to published procedures.20 For intravenous bone marrow engraftment, nonobese diabetic/severe combined immunodeficient mice were acclimated for 2 weeks before pretreatment with 150 mg/kg cyclophosphamide delivered intraperitoneally once a day for 2 days. After a 48-hour rest period, animals were given an intravenous injection of 5 × 10^6 MV4-11 cells into the tail vein. AC220 was formulated and delivered as described for pharmacokinetic studies .

储存与操作

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储存	-20°C
有效期	12 months from date of receipt.
免责声明	For research use only

别名

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AC220

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C₂₉H₃₂N₆O₄S
可选规格： 5 mg, 10 mg, 25 mg, 50 mg, 100 mg, 200 mg, 500 mg, 1 g

质量保证

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化合物标识

PubChem CID

24889392 ↗

关键属性

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暂无计算属性。

实验方案信息

查看更多实验方案

CAS 号：	2292116-14-2
MW:	607.68
分子式：	C₃₀H₃₃N₅O₇S

CAS 号：	1132827-21-4
MW:	633.59
分子式：	C₂₉H₃₄Cl₂N₆O₄S

纯度：	>99.99% (May vary between batches)
CAS 号：	1137212-79-3
MW:	616.797
分子式：	C₃₄H₄₈N₈O₃

纯度：	>98% (HPLC)
CAS 号：	1429882-07-4
MW:	488.67
分子式：	C₂₉H₄₀N₆O

Quizartinib

描述

研究领域

图片与验证

关键属性

生物活性

储存与操作

别名

相似产品

Desmorpholinyl Quizartinib-PEG2-COOH [orb1691031]

Quizartinib HCl [orb1738080]

Plogosertib [orb1738081]

MRX-2843 [orb1220102]

Quizartinib [orb1223539]

质量保证

化合物标识

关键属性

实验方案信息

可选规格