CAS號(hào)	686770-61-6	產(chǎn)地	國(guó)產(chǎn)
規(guī)格	5mg	級(jí)別	化工級(jí)
證書	ISO系列證書

IWP-2

IWP-2 是 Wnt 加工和分泌的抑制劑，其 IC₅₀ 為 27 nM。IWP-2 靶向膜結(jié)合的 O-酰基轉(zhuǎn)移酶 porcupine (Porcn)，從而阻止關(guān)鍵的 Wnt 配體棕櫚糖基化。IWP-2 還是一種具有 ATP 競(jìng)爭(zhēng)能力的 CK1δ 抑制劑，對(duì)于 ^M82FCK1δ 的 IC₅₀ 為 40 nM。

生物活性

IWP-2 is an inhibitor of Wnt processing and secretion with an IC₅₀ of 27 nM. IWP-2 targets the membrane-bound O-acyltransferase porcupine(Porcn) and thus preventing a crucial Wnt ligand palmitoylation. IWP-2 is also an ATP-competitive CK1δ inhibitor with an IC₅₀ of 40 nM for the gatekeeper mutant ^M82FCK1δ^[1]^[2].

IC₅₀ & Target

CK1δ

40 nM (IC₅₀)

體外研究(In Vitro)

IWP-2 inhibits the proliferation of the investigated cell lines within the single digit μM range. IWP-2 inhibits cell proliferation in A818-6, MiaPaCa2, Panc-1, Panc-89, HT29, HEK293, SW620 and Capan cell with EC₅₀s of 8.96 μM, 1.90 μM, 2.33 μM, 3.86 μM, 4.67 μM, 2.76 μM, 1.90 μM and 2.05 μM, respectively^[2].
Panc-1 cells are either untreated or treated with 2.33 μM IWP-2 for 48 h. In IWP-2 treated cells, the CK1δ kinase peak activity is reduced to approximately 66% residual activity compared to the activity in untreated cells, respectively. IWP-2 reduces the activity of CK1δ in Panc1 cells^[2].

體內(nèi)研究(In Vivo)

To evaluate the efficacy of IWP-2 in vivo, 200 μL each of IWP-2-liposome or free liposome i separately injected into C57BL/6 mice intraperitoneally about 2 h before injection of a similar volume of either blue-dye-filled latex beads or E. coli DH5α. IWP-2 causes significant reduction in the uptake of blue beads as well as E. coli as assessed by CFUs in peritoneal lavage cells within 2 h. In addition, the levels of TNF-α and IL-6 in the lavage fluid of the corresponding mice are reduced by 2-4-fold compared with control values. Interestingly, IWP-2 even induces a considerable increase in secretion of the anti-inflammatory cytokine IL-10^[3].

分子量：466.60

性狀：Solid

Formula：C₂₂H₁₈N₄O₂S₃

CAS 號(hào)：686770-61-6

運(yùn)輸條件：Room temperature in continental US; may vary elsewhere.

儲(chǔ)存方式

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

溶解性數(shù)據(jù)

In Vitro:

DMF : 12.5 mg/mL (26.79 mM; ultrasonic and warming and heat to 60°C)

DMSO : 2 mg/mL (4.29 mM; Need ultrasonic)

配制儲(chǔ)備液

濃度溶劑體積質(zhì)量	1 mg	5 mg	10 mg

1 mM	2.1432 mL	10.7158 mL	21.4316 mL
5 mM	0.4286 mL	2.1432 mL	4.2863 mL
10 mM	0.2143 mL	1.0716 mL	2.1432 mL

請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；一旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
儲(chǔ)備液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)月內(nèi)使用，-20°C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)月內(nèi)使用。

參考文獻(xiàn)

[1]. Chen B, et al. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat Chem Biol. 2009 Feb;5(2):100-7. [Content Brief]

[2]. García-Reyes B, et al. Discovery of Inhibitor of Wnt Production 2 (IWP-2) and Related Compounds As Selective ATP-Competitive Inhibitors of Casein Kinase 1 (CK1) δ/ε. J Med Chem. 2018 May 10;61(9):4087-4102. [Content Brief]

[3]. Maiti G, et al. The Wingless homolog Wnt5a stimulates phagocytosis but not bacterial killing. Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16600-5. [Content Brief]

注：產(chǎn)品僅用于科研