IWP-3 is an potent inhibitor of Wnt production with an IC50 of 40 nM. IWP-3 inhibits Porcupine (Porcn) function thereby blocking palmitoylation of Wnt proteins. IWP-3 inhibits CK1γ3 and CK1ε only moderately and does not inhibit CK1α[1][2].
IC50 & Target[1]
Wnt
40 nM (IC50)
分子量
484.59
Formula
C22H17FN4O2S3
CAS 号
687561-60-0
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Baozhi Chen, et al. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat Chem Biol. 2009 Feb;5(2):100-7.
[2]. Balbina García-Reyes, 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.
IWP-O1 is a highly potent Porcupine (Porcn) inhibitor, with an EC50 of 80 pM in L-Wnt-STF cells. IWP-O1 prevents the secretion of Wnt proteins. IWP-O1 suppresses the phosphorylation of Dvl2/3 and LRP6 in HeLa cells[1].
IC50 & Target
EC50: 80 pM (Porcn)[1].
体外研究 (In Vitro)
IWP-O1 (17) suppresses Wnt signaling in L-Wnt-STF cells with an EC50 value of 80 pM, 2.5 times more active than the investigational drug LGK974[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
432.48
Formula
C26H20N6O
CAS 号
2074607-48-8
运输条件
Room temperature in continental US; may vary elsewhere.
IWP L6 (Porcn Inhibitor III) is a Porcn inhibitor with an EC50 of 0.5 nM.
IC50 & Target
EC50 Value: 0.5 nM[1]
体外研究 (In Vitro)
IWP-L6 (Porcn Inhibitor III) effectively suppressed the phosphorylation of dishevelled 2 (Dvl2) in HEK293 cells, a biochemical event associated with many Wnt-dependent cellular responses. IWP-L6 inhibits Wnt mediated branching morphogenesis in cultured embryonic kidneys [1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
IWP-L6 (Porcn Inhibitor III) is stable in human plasma over 24 h, it was rapidly metabolized in rat plasma (t1/2 = 190 min), murine plasma (t1/2 = 2 min), and the murine liver S9 fractions (t1/2 = 26 min). The major metabolites are the amide cleavage products. Similar species-dependent metabolitic profiles due to the involvement of carboxylesterase (CES) have been reported with other drug candidates. Despite its modest metabolic stability in mouse-derived plasma, IWP-L6 was highly active in zebrafish. IWP-L6 exhibited more potent activity[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
472.58
Formula
C25H20N4O2S2
CAS 号
1427782-89-5
运输条件
Room temperature in continental US; may vary elsewhere.
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
Wnt
27 nM (IC50)
CK1δ
40 nM (IC50)
体外研究 (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].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (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].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
466.60
Formula
C22H18N4O2S3
CAS 号
686770-61-6
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMF : 12.5 mg/mL (26.79 mM; ultrasonic and warming and heat to 60°C)
[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.
[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.
[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.
Cell Assay [2]
The human RCC cell lines 786O and Caki-2 (5×103) are seeded into 96-well plates. Cell viability is estimated by MST assay after Caki-2 acells are incubated with ncreasing concentrations of LEF together with 20 μM IWP-2 for 48 h.After treatment, 10 μL MTS is added into each well for 2 h incubation. The absorbance is measured using a model ELX800 Micro Plate Reader at 490 nm. For colony formation assay, Caki-2 cells are trypsinized to single cell suspensions and seeded into fresh 6-well plates at 1000 cells/well. Then cells are incubated with LEF at depicted concentrations for 7 days. Colonies are fixed with absolute methanol for 15 min and then stained with 0.1% crystal violet for 20 min. After washing with PBS three times, the colonies with a diameter over 2 mm are visualized by a digital camera[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[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.
[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.
[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.
IWP-4 is a small molecule Wnt inhibitor with an IC50 of 25 nM.
IC50 & Target
IC50: 25 nM (Wnt)[1]
体外研究 (In Vitro)
IWP-4 is a small molecule Wnt inhibitor with an IC50 of 25 nM. IWP-4 induces the expression of cardiac markers, including cardiac troponin I (CTNI) and cardiac myosin heavy chain bright cells (MYHhi +). IWP-4 also results in the appearance of beating foci (0.44±0.10 SEM beats per second), which is absent in all cultures not receiving IWP-4. Further, flow cytometric analysis shows that there are significantly more MYHlo + cells in IWP-4 treated cultures (P<0.0002) compare with untreated cultures at day 16, being 17.0±1.3 SD% and 5.4±1.4 SD%, respectively. Quantification of NKX2-5 protein expression shows that 63% (481/817) of IWP-4 treated cells display nuclear NKX2-5 expression[1]. Mesenchymal precursor cells (MPCs) treated with IWP-4 show no significant changes in the expression of AXIN2, CTNNB1 and GSK3B as compare to osteogenic medium alone on day 7, but MPCs treated with IWP-4 express elevates levels of DKK1 and GSK3β on day 21. IWP-4 also causes a significant down regulation of SPARC and COL1A1[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
496.62
Formula
C23H20N4O3S3
CAS 号
686772-17-8
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Hudson J, et al. Primitive cardiac cells from human embryonic stem cells. Stem Cells Dev. 2012 Jun 10;21(9):1513-23.
[2]. Frith JE, et al. Microbioreactor array screening of Wnt modulators and microenvironmental factors in osteogenic differentiation of mesenchymal progenitor cells. PLoS One. 2013 Dec 23;8(12):e82931.
Cell Assay [1]
hESC cultures are obtained in mTeSR-1 medium and expanded with daily medium exchange until colonies reach the desired level of confluence (~70% to 80%). At this time (marked day 0), mTeSR-1 is replaced with a basal medium comprised of RPMI 1640 medium supplemented with 2% B27 supplement and 1% penicillin/streptomycin. 20 ng/mL BMP-4 and/or 6 ng/mL activin A are added to the basal medium for primitive streak induction, and exchanged daily until day 3. Then, basal media with or without 5 mM IWP-4 is added to the cells and exchanged every 2 days [dimethyl sulfoxide (DMSO) at the same concentration is used as a vehicle control] until day 15, after which basal medium is supplied every 2 days[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Hudson J, et al. Primitive cardiac cells from human embryonic stem cells. Stem Cells Dev. 2012 Jun 10;21(9):1513-23.
[2]. Frith JE, et al. Microbioreactor array screening of Wnt modulators and microenvironmental factors in osteogenic differentiation of mesenchymal progenitor cells. PLoS One. 2013 Dec 23;8(12):e82931.
