UNC2025 hydrochloride

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本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

2070015-17-5

UNC2025 hydrochloride 是一种强效、ATP 竞争性，高口服活性的Mer/Flt3抑制剂，IC₅₀值分别为 0.74 nM 和 0.8 nM。UNC2025 hydrochloride 对 MERTK 的选择性是 Axl 的 45 倍(IC₅₀=122nM;K_i=13.3 nM)。UNC2025 hydrochloride 具有良好的 PK 特性，可用于急性白血病的研究。

生物活性

UNC2025 hydrochloride is a potent, ATP-competitive, and highly orally activeMer/Flt3inhibitor withIC₅₀values of 0.74 nM and 0.8 nM, respectively. UNC2025 hydrochloride is >45-fold selectivity for MERTK relative to Axl (IC₅₀= 122 nM;K_i = 13.3 nM). UNC2025 hydrochloride exhibits an excellent PK properties, and can be used for the investigation of acute leukemia^[1].

IC₅₀& Target

IC50: 0.74 nM (Mer); 0.8 nM (Flt3)^[1]

体外研究
(In Vitro)

UNC2025 is against FLT3, MER, AXL, TRKA, TRKC, QIK, TYRO3, SLK, NuaK1, KIT and Met with IC₅₀values of 0.35 nM, 0.46 nM, 1.65 nM, 1.67 nM, 4.38 nM, 5.75 nM, 5.83 nM, 6.14 nM, 7.97 nM , 8.18 nM and 364 nM, respectively^[1].
UNC2025 (0-60 nM; 1 hour) mediates potent inhibition of Mer phosphorylation with an IC₅₀ of 2.7 nM in 697 B-ALL cells^[1].
UNC2025 (0-60 nM; 1 hour) results in decreased phosphorylation of Flt3 with an IC₅₀ of 14 nM in Flt3-ITD positive Molm-14 acute myeloid leukemia cells^[1].
UNC2025 (3 nM-3 μM; 1 hour) decreases p-MEK, p-AXL, p-TYRO3 expression as a concentration manner in 32D Cells^[1].
UNC2025 (14 nM–10 μM; 48 hours) inhibits MERTK signaling and colony-forming potential in a MERTK-expressing patient sample with a 20-fold difference in sensitivity of MERTK-expressing leukemia blasts relative to normal cord or marrow blood mononuclear cells^[2].
UNC2025 (25-300 nM; 1 hour) mediates potent and dose-dependent decreases in MERTK phosphorylation/activation in both cell lines and inhibition of MERTK correlated with decreased phosphorylation of previously reported MERTK-dependent signaling components STAT6, AKT, and ERK1/2^[2].

Western Blot Analysis^[1]

Cell Line:	32D Cells
Concentration:	0 nM, 3 nM, 10 nM, 20 nM, 30 nM, 100 nM, 1000 nM, 3000 nM
Incubation Time:	1 hour
Result:	Inhibited p-MEK, p-AXL, p-TYRO3 expression.

Cell Proliferation Assay^[1]

Cell Line:	Mononuclear cells
Concentration:	14 nM–10 μM
Incubation Time:	48 hours
Result:	Showed IC₅₀values ranged from 9.0 nM to >10 μM with a median IC₅₀of 2.38 μM.

Western Blot Analysis^[2]

Cell Line:	Kasumi-1 AML and 697 B-ALL cells
Concentration:	25-300 nM
Incubation Time:	48 hours
Result:	Decresed p-MERTK, p-STAT6, p- AKT and p-ERK1/2 expression as a dose-dependent manner.

体内研究
(In Vivo)

UNC2025 (intravenous injection or oral adminstration; 3 mg/kg) exhibits an excellent PK properties: low clearance (9.2 mL/min kg), longer half-life (3.8 h), and high oral exposure (100%), it shows T_max, C_max, and AUClast 0.50 hour, 1.6 μM, and 9.2 h μM, respectively^[2].
UNC2025 (orally adminstration; 50 or 75 mg/kg; 34 and 70 days) mediates a statistically significant dose-dependent reduction in tumor burden relative to vehicle. mediates dose-dependent increases in median survival from 26 days after initiation of treatment in vehicle-treated mice, to 34 and 70 days in mice treated with 50 or 75 mg/kg UNC2025, respectively^[2].

Animal Model:	NSG mice injected with 697 B-ALL cells^[2]
Dosage:	50 or 75 mg/kg
Administration:	Oral adminstration
Result:	Delayed the disease progression.

分子量

513.12

性状

Solid

Formula

C₂₈H₄₁ClN₆O

CAS 号

2070015-17-5

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

溶解性数据

In Vitro:

H₂O : 55 mg/mL(107.19 mM;Need ultrasonic)

DMSO : 10 mg/mL(19.49 mM;Need ultrasonic)

配制储备液

浓度溶剂体积质量

1 mg

5 mg

10 mg

1 mM	1.9489 mL	9.7443 mL	19.4886 mL
5 mM	0.3898 mL	1.9489 mL	3.8977 mL
10 mM	0.1949 mL	0.9744 mL	1.9489 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℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 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： PBS
Solubility: 100 mg/mL (194.89 mM); Clear solution; Need ultrasonic
2.
请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline
Solubility: ≥ 1 mg/mL (1.95 mM); Clear solution
此方案可获得 ≥ 1 mg/mL (1.95 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 10.0 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
3.
请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline)
Solubility: ≥ 1 mg/mL (1.95 mM); Clear solution
此方案可获得 ≥ 1 mg/mL (1.95 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 10.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明

*以上所有助溶剂都可在本网站选购。