Asnuciclib CDKI-73; LS-007|cas:1421693-22-2|西域试剂

Asnuciclib CDKI-73; LS-007,99.76%

产品编号：Bellancom-12445| CAS NO：1421693-22-2| 分子式：C₁₅H₁₅FN₆O₂S₂| 分子量：394.45

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货号	价格	库存与货期
Bellancom-12445	￥2333.00	杭州北京（现货）
Bellancom-12445	￥3500.00	杭州北京（现货）
Bellancom-12445	￥5000.00	杭州北京（现货）
Bellancom-12445	￥0.00	杭州北京（现货）
Bellancom-12445	￥0.00	杭州北京（现货）

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Asnuciclib CDKI-73; LS-007

产品介绍

Asnuciclib (CDKI-73; LS-007) 是具有口服活性的、高效的 CDK9 抑制剂，其对CDK9、CDK1 和 CDK2 的 K_i 值分别为 4 nM、4 nM 和 3 nM。CDKI-73 可下调 RNA 聚合酶 II 的磷酸化。Asnuciclib 也是一种 Rab11 的抑制剂。

生物活性

Asnuciclib (CDKI-73; LS-007) is an orally active and highly efficacious CDK9 inhibitor, with K_i values of 4 nM, 4 nM and 3 nM for CDK9, CDK1 and CDK2, respectively. Asnuciclib down-regulates the RNAPII phosphorylation. Asnuciclib is also a novel pharmacological inhibitor of Rab11 cargo delivery and innate immune secretion^[4].

体外研究

Asnuciclib is highly cytotoxic to primary leukemia cells derived from CLL patients (mean LD₅₀ = 0.08 μM) and shows>500-fold selectivity for primary leukemia cells over normal B-lymphocytes (LD₅₀=40.5 μM).
Asnuciclib (0.1 μM, 4 h) inhibits the phosphorylation of serine 2 of RNA polymerase II and MCL1 protein expression in CLL cells.
Asnuciclib induced caspase-dependent apoptosis that was preceded by dephosphorylation of cdk9 and serine 2 of RNA polymerase II.
Asnuciclib is highly effective against all cell lines tested with an IC₅₀ in the range of 0.012-0.517 μM; in particular three MLL-AML cell lines, namely MOLM13, MV4-11 and THP-1, were highly sensitive to CDKI-73 with IC₅₀ values <0.062 μM.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay.

Cell Line:	CLL cells.
Concentration:	0-1 μM.
Incubation Time:	48 h.
Result:	Shows preferential cytotoxicity in CLL cells.

体内研究
(In Vivo)

Asnuciclib (25, 50, 100 mg/kg) markedly decreases tumor growth in a dose-dependent manner and results in a prolongation of animal life span (P < 0.001) without causing body weight loss and other overt toxicities..

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	MV4-11 tumor bearing mice.
Dosage:	25 mg/kg.
Administration:	Orally once everyday for 33 days.
Result:	Caused a remarkable delay in tumor growth compared to vehicle-treated mice, as reflected in a percentage for the mean tumor volume in treated to control mice of 43% at day 31.

Animal Model:	Balb/C mice aged 6-8 weeks.
Dosage:	2 mg/kg (IV), 10, 20 and 40 mg/kg (PO). (Pharmacokinetic Analysis.)
Administration:	IV and PO, single dose.
Result:	The C_max increased from 1.29 to 3.66 μM at a mean time of 1 h and the area under the curve (AUC) of CDKI-73 increased from 3.51 to 12.8 μM.h when the oral dose was escalated from 10 to 40 mg/kg. CDKI-73 was eliminated from plasma with a mean terminal half-life (T1/2) of 2 h. Its oral bioavailability (F) ranged from 54 to 85% across the three doses.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	MV4-11 tumor bearing mice.
Dosage:	25 mg/kg.
Administration:	Orally once everyday for 33 days.
Result:	Caused a remarkable delay in tumor growth compared to vehicle-treated mice, as reflected in a percentage for the mean tumor volume in treated to control mice of 43% at day 31.

Animal Model:	Balb/C mice aged 6-8 weeks.
Dosage:	2 mg/kg (IV), 10, 20 and 40 mg/kg (PO). (Pharmacokinetic Analysis.)
Administration:	IV and PO, single dose.
Result:	The C_max increased from 1.29 to 3.66 μM at a mean time of 1 h and the area under the curve (AUC) of CDKI-73 increased from 3.51 to 12.8 μM.h when the oral dose was escalated from 10 to 40 mg/kg. CDKI-73 was eliminated from plasma with a mean terminal half-life (T1/2) of 2 h. Its oral bioavailability (F) ranged from 54 to 85% across the three doses.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	MV4-11 tumor bearing mice.
Dosage:	25 mg/kg.
Administration:	Orally once everyday for 33 days.
Result:	Caused a remarkable delay in tumor growth compared to vehicle-treated mice, as reflected in a percentage for the mean tumor volume in treated to control mice of 43% at day 31.

Animal Model:	Balb/C mice aged 6-8 weeks.
Dosage:	2 mg/kg (IV), 10, 20 and 40 mg/kg (PO). (Pharmacokinetic Analysis.)
Administration:	IV and PO, single dose.
Result:	The C_max increased from 1.29 to 3.66 μM at a mean time of 1 h and the area under the curve (AUC) of CDKI-73 increased from 3.51 to 12.8 μM.h when the oral dose was escalated from 10 to 40 mg/kg. CDKI-73 was eliminated from plasma with a mean terminal half-life (T1/2) of 2 h. Its oral bioavailability (F) ranged from 54 to 85% across the three doses.

性状

Solid

溶解性数据

In Vitro:

DMSO : ≥ 52 mg/mL (131.83 mM)

* "≥" means soluble, but saturation unknown.

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.5352 mL	12.6759 mL	25.3518 mL
5 mM	0.5070 mL	2.5352 mL	5.0704 mL
10 mM	0.2535 mL	1.2676 mL	2.5352 mL

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (stored under nitrogen)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.

请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.67 mg/mL (6.77 mM); Clear solution

此方案可获得 ≥ 2.67 mg/mL (6.77 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 26.7 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液