Narazaciclib | ON 123300 | CDK4/ARK5 Inhibitor | AmBeed-信号通路专用抑制剂

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Narazaciclib {[allProObj[0].p_purity_real_show]}

货号：A414519 同义名： ON 123300

ON123300 is a potent and multi-targeted kinase inhibitor which inhibits CDK4, Ark5, PDGFRβ, FGFR1, RET, and Fyn with IC50 of 3.9 nM, 5 nM, 26 nM, 26 nM, 9.2 nM and 11nM respectively.

Narazaciclib 化学结构
CAS号：1357470-29-1

Narazaciclib 3D分子结构
CAS号：1357470-29-1

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Narazaciclib 纯度/质量文件产品仅供科研

货号：A414519 标准纯度： {[allProObj[0].p_purity_real_show]} 产品说明书

批次查询：批次纯度: COA SDS NMR HPLC CNMR LC-MS

全球学术期刊中引用的产品: • Nat. Biomed. Eng., 2024, 8, 1412-1424. Ambeed. [ A538667 , A631746 ]; • JMC, 2024. Ambeed. [ A833302 , A475501 , A341986 , A356070 ]; • BMC Cancer, 2024, 24(1): 1415. Ambeed. [ A809692 , A209020 ]; • J. Am. Soc. Mass Spectrom., 2024, 35(12): 3192-3202. Ambeed. [ A166127 , A902473 , A753371 , A961334 , A292945 , A230770 , A300620 , A1114580 , A1159765 , A206238 ]; • PloS One, 2024, 19(11): e0308060. Ambeed. [ A302917 ]; 更多 >

CDK 亚型比较

产品名称	Cdc ↓ ↑	CDK1 ↓ ↑	CDK19 ↓ ↑	CDK2 ↓ ↑	CDK3 ↓ ↑	CDK4 ↓ ↑	CDK5 ↓ ↑	CDK6 ↓ ↑	CDK7 ↓ ↑	CDK8 ↓ ↑	CDK9 ↓ ↑	CLK ↓ ↑	其他靶点	纯度
XL413 hydrochloride	++++ Cdc7, IC50: 3.4 nM													99%+
SU9516		+++ CDK1, IC50: 40 nM		+++ CDK2, IC50: 22 nM		++ CDK4, IC50: 200 nM								99%+
RO-3306		+++ CDK1, Ki: 20 nM											ERK,SGK	98%
R547		++++ CDK1/CyclinB, Ki: 2 nM		++++ CDK2/CyclinE, Ki: 3 nM		++++ CDK4/CyclinD1, Ki: 1 nM								99%+
BMS-265246		++++ CDK1/CyclinB, IC50: 6 nM		++++ CDK2/CyclinE, IC50: 9 nM		+ CDK4/CyclinD, IC50: 230 nM								99%+
NU6027		+ CDK1, Ki: 2.5 μM		+ CDK2, Ki: 1.3 μM									DNA-PK	98%
Purvalanol A	++++ Cdc2/CyclinB, IC50: 4 nM			+++ CDK2/CyclinE, IC50: 35 nM CDK2/CyclinA, IC50: 70 nM		+ CDK4/CyclinD1, IC50: 850 nM								99%+
SCH900776				++ CDK2, IC50: 0.16 μM										99%+
AUZ 454				++++ CDK2(C118L), Kd: 18.6 nM CDK2(A144C), Kd: 9.7 nM										99%+
A-674563 HCl				++ CDK2, Ki: 46 nM									PKA	98%
JNJ-7706621		++++ CDK1/CyclinB, IC50: 9 nM		++++ CDK2/CyclinE, IC50: 3 nM CDK2/CyclinA, IC50: 4 nM	++ CDK3/CyclinE, IC50: 58 nM	+ CDK4/CyclinD1, IC50: 253 nM		++ CDK6/CyclinD1, IC50: 175 nM						99%+
AT7519		++ CDK1/CyclinB, IC50: 210 nM		++ CDK2/CyclinA, IC50: 47 nM	+ CDK3/CyclinE, IC50: 360 nM	++ CDK4/CyclinD1, IC50: 100 nM	+++ CDK5/p35, IC50: 13 nM	++ CDK6/CyclinD3, IC50: 170 nM			++++ CDK9/CyclinT, IC50: <10 nM			98+%
PHA-793887		++ CDK1/CyclinB, IC50: 60 nM		++++ CDK2/CyclinE, IC50: 8 nM CDK2/CyclinA, IC50: 8 nM		++ CDK4/CyclinD1, IC50: 62 nM	++++ CDK5/p25, IC50: 5 nM		++++ CDK7/CyclinH, IC50: 10 nM		++ CDK9/CyclinT1, IC50: 138 nM			99%+
Milciclib		+ CDK1/CyclinB, IC50: 398 nM		++ CDK2/CyclinE, IC50: 363 nM CDK2/CyclinA, IC50: 45 nM		++ CDK4/CyclinD1, IC50: 160 nM	+ CDK5/p35, IC50: 265 nM		++ CDK7/CyclinH, IC50: 150 nM					99%+
Kenpaullone		+ CDK1/CyclinB, IC50: 0.4μM		+ CDK2/CyclinE, IC50: 7.5μM CDK2/CyclinA, IC50: 0.68μM			+ CDK5/p35, IC50: 0.85μM							98%
SNS-032				+++ CDK2/CyclinE, IC50: 48 nM CDK2/CyclinA, IC50: 38 nM			+ CDK5/p35, IC50: 340 nM		++ CDK7/CyclinH, IC50: 62 nM		++++ CDK9/CyclinT, IC50: 4 nM			99%+
Dinaciclib		++++ CDK1, IC50: 3 nM		++++ CDK2, IC50: 1 nM			++++ CDK5, IC50: 1 nM				++++ CDK9, IC50: 4 nM			99%+
PHA-767491 hydrochloride	++++ Cdc7, IC50: 10 nM	+ CDK1, IC50: 250 nM		+ CDK2, IC50: 240 nM			+ CDK5, IC50: 460 nM				+++ CDK9, IC50: 34 nM		MK2	98%
(R)-Roscovitine	+ Cdc2/CyclinB, IC50: 0.65 μM			+ CDK2/CyclinE, IC50: 0.7 μM CDK2/CyclinA, IC50: 0.7 μM			++ CDK5/p35, IC50: 0.16 μM							99%+
Narazaciclib						++++ CDK4/CyclinD1, IC50: 3.87 nM		++++ CDK6/CyclinD1, IC50: 9.82 nM					RET	99%+
Palbociclib						++++ CDK4/CyclinD3, IC50: 9 nM CDK4/CyclinD1, IC50: 11 nM		+++ CDK6/CyclinD2, IC50: 15 nM						99%
Abemaciclib						++++ CDK4, IC50: 2 nM		++++ CDK6, IC50: 10 nM						99%
Ribociclib						++++ CDK4, IC50: 10 nM		+++ CDK6, IC50: 39 nM						98%
Palbociclib isethionate						++++ CDK4/CyclinD3, IC50: 9 nM CDK4/CyclinD1, IC50: 11 nM		+++ CDK6/CyclinD2, IC50: 15 nM						99%+
BS-181 HCl									+++ CDK7, IC50: 21 nM					99%+
(E/Z)-THZ1 dihydrochloride									++++ CDK7, IC50: 3.2 nM					99%+
LDC4297									++++ CDK7, IC50: 0.13 nM					99%+
Senexin A			+ CDK19, Kd: 0.31 μM							+ CDK8, Kd: 0.83 μM				98+%
MSC2530818										++++ CDK8, IC50: 2.6 nM				99%+
Wogonin											✔			99%+
Riviciclib HCl		++ CDK1/CyclinB, IC50: 79 nM		+ CDK2/CyclinE, IC50: 2.54 μM CDK2/CyclinA, IC50: 224 nM		++ CDK4/CyclinD1, IC50: 63 nM		+ CDK6/CyclinD3, IC50: 396 nM	+ CDK7/CyclinH, IC50: 2.87 μM		+++ CDK9/CyclinT1, IC50: 20 nM			99+%
LDC000067				+ CDK2, IC50: 2.441 μM							++ CDK9, IC50: 44 nM			98%
Flavopiridol		+++ CDK1, IC50: 40 nM		+++ CDK2, IC50: 40 nM		+++ CDK4, IC50: 40 nM		+++ CDK6, IC50: 40 nM	+ CDK7, IC50: 300 nM		+++ CDK9, IC50: 20 nM			99%+
LY2857785									+ CDK7, IC50: 0.246 μM	+++ CDK8, IC50: 0.016 μM	+++ CDK9, IC50: 0.011 μM			99%+
AZD-5438		+++ CDK1, IC50: 16 nM		++++ CDK2, IC50: 6 nM							+++ CDK9, IC50: 20 nM			99%+
ML167												++ CLK4, IC50: 136 nM Dyrk1B , IC50: 1648 nM		99%+
(E/Z)-TG003												+++ mCLK1, IC50: 200 nM mCLK4, IC50: 15 nM		99%+
1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多，抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用，但抑制强度暂时没有相关数据。

Narazaciclib 生物活性

靶点

FGFR1

FGFR1, IC50:26 nM
CDK4

CDK4/CyclinD1, IC50:3.87 nM
CDK6

CDK6/CyclinD1, IC50:9.82 nM

描述

The cyclin-dependent kinases (CDKs) have a central role in coordinating the eukaryotic cell division cycle, and also serve to integrate diverse growth-regulatory signals^[5]. ON123300 is an effective multi-target kinase inhibitor against CDK4 and ARK5, two kinases intimately associated with growth, survival and metastasis of human tumor cells with IC₅₀s of 3.9 nM, 5 nM, respectively. Z138C cells treated with ON123300 for 24 hours accumulated in the G₁ phase at lower concentrations (0.1–1.0 µM), at higher concentrations of this compound, a large proportion of the cells progressed through the S and G₂/M phases of the cell cycle and eventually accumulated in the sub-G₁ phase, suggesting an induction of apoptosis. Granta 519 and Z138C cells were treated with increasing concentrations of ON123300 for 24 hours. ON123300 repressed the phosphorylation of pRb and p130 in a dose-dependent manner suggesting that ON123300 inactivated the Rb (Retinoblastoma family of proteins) pathway due to the inhibition of CDK4 in the two MCL (mantle cell lymphoma) cell lines. Mice with tumor xenografts were randomly assigned into 2 treatment groups and treated daily with either water (vehicle) or ON123300 (100mg/kg) on a daily basis. Treatment with ON123300 significantly inhibited (p<0.05) tumor growth over a 2-week period, suggesting that this compound is a potent inhibitor of MCL proliferation in vivo^[6].

Narazaciclib 动物研究

Dose

Rat: 5 mg/kg, 10 mg/kg^[3] (i.v.); 25 mg/kg, 200 mg/kg^[3] (p.o.) Mice: 125 mg/kg^[4] (p.o.)

Administration

i.v., p.o.

Pharmacokinetics

Animal	Rats^[3]
Dose	10 mg/kg
Administration	i.v.
V	4.72 ± 0.99 L/kg (male) 2.85 ± 0.17 L/kg (female)
T_1/2	0.71 ± 0.10 h (male) 0.87 ± 0.12 h (female)
CL	75.90 ± 4.66 ml/min/kg (male) 38.44 ± 4.60 ml/min/kg (female)
AUC_0→∞	2200 ± 136 ng·h/ml (male) 4399 ± 542 ng·h/ml (female)

Narazaciclib 参考文献

[1]Zhang X, Lv H, et al. Preclinical pharmacological evaluation of a novel multiple kinase inhibitor, ON123300, in brain tumor models. Mol Cancer Ther. 2014 May;13(5):1105-16.

[2]Lv H, Zhang X, et al. Integrated pharmacokinetic-driven approach to screen candidate anticancer drugs for brain tumor chemotherapy. AAPS J. 2013 Jan;15(1):250-7.

[3]Mudunuru J, Ren C, et al. Effect of Gender on the Pharmacokinetics of ON 123300, A Dual Inhibitor of ARK5 and CDK4/6 for the Treatment of Cancer, in Rats. Eur J Drug Metab Pharmacokinet. 2019 Aug;44(4):531-538.

[4]ON 123300, an Orally Administered Novel CDK4/6 + ARK5 Inhibitor, Exhibits Potent Antitumor Activity In Vivo: Comparative Studies with Palbociclib

[5]Pavletich NP. Mechanisms of cyclin-dependent kinase regulation: structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors. J Mol Biol. 1999 Apr 16;287(5):821-8. doi: 10.1006/jmbi.1999.2640. PMID: 10222191.

[6]Divakar SK, Ramana Reddy MV, Cosenza SC, Baker SJ, Perumal D, Antonelli AC, Brody J, Akula B, Parekh S, Reddy EP. Dual inhibition of CDK4/Rb and PI3K/AKT/mTOR pathways by ON123300 induces synthetic lethality in mantle cell lymphomas. Leukemia. 2016 Jan;30(1):86-93. doi: 10.1038/leu.2015.185. Epub 2015 Jul 15. PMID: 26174628; PMCID: PMC4703501.

Narazaciclib 实验方案

计算器

存储液制备

1mg

5mg

10mg

1 mM

5 mM

10 mM

2.33mL

0.47mL

0.23mL

11.64mL

2.33mL

1.16mL

23.28mL

4.66mL

2.33mL

Narazaciclib 技术信息

CAS号	1357470-29-1
分子式	C₂₄H₂₇N₇O
分子量	429.517

别名	ON 123300
运输	蓝冰

存储条件

液体 -20°C:3-6个月-80°C:12个月

粉末 Keep in dark place,Inert atmosphere,Room temperature

溶解度

DMSO: 16 mg/mL(37.25 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

动物实验配方

Narazaciclib {[allProObj[0].p_purity_real_show]}

Narazaciclib 纯度/质量文件产品仅供科研

全球学术期刊中引用的产品

Narazaciclib 质控信息

Narazaciclib 生物活性

Narazaciclib 动物研究

Narazaciclib 参考文献

Narazaciclib 实验方案

Narazaciclib 技术信息

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FGFR1	FGFR1, IC50:26 nM
CDK4	CDK4/CyclinD1, IC50:3.87 nM
CDK6	CDK6/CyclinD1, IC50:9.82 nM

Narazaciclib {[allProObj[0].p_purity_real_show]}

Narazaciclib 纯度/质量文件 产品仅供科研

全球学术期刊中引用的产品

Narazaciclib 质控信息

Narazaciclib 生物活性

Narazaciclib 动物研究

Narazaciclib 参考文献

Narazaciclib 实验方案

Narazaciclib 技术信息

最近浏览的产品

大规格询价

摩尔计算器

靶点

总药量计算器

工作液计算器

细胞研究

临床研究

确认信息

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Narazaciclib 纯度/质量文件产品仅供科研