OM-153 is a potent tankyrase inhibitor with IC50s of 13 and 2 nM for tankyrase 1 and tankyrase 2, respectively. OM-153 shows inhibition of WNT/β-catenin signaling and proliferation in COLO 320DM[1].
IC50 & Target[1]
TNKS1
13 nM (IC50)
TNKS2
2 nM (IC50)
体外研究 (In Vitro)
OM-153 shows picomolar IC50 inhibition (0.63 nM) in a cellular (HEK293) WNT/β-catenin signaling reporter assay, no off-target liabilities, overall favorable absorption, distribution, metabolism, and excretion (ADME) properties, and an improved pharmacokinetic profile in mice[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
509.53
Formula
C28H24FN7O2
CAS 号
2406278-81-5
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]. Leenders RGG, et al. Development of a 1,2,4-Triazole-Based Lead Tankyrase Inhibitor: Part II. J Med Chem. 2021;64(24):17936-17949.
RK-287107 is a potent and specific tankyrase inhibitor with IC50s of 14.3 and 10.6 nM for tankyrase-1 and tankyrase-2, respectively. RK-287107 blocks colorectal cancer cell growth[1].
IC50 & Target[1]
tankyrase-1
14.3 nM (IC50)
tankyrase-2
10.6 nM (IC50)
体外研究 (In Vitro)
RK-87107 (0.01-10 μM; 12 hours) shows an antiproliferative effect on colorectal cancer cells harboring short adenomatous polyposis coli (APC) mutations. The 50% growth inhibition (GI50) value of RK-287107 on COLO-320DM cells is 0.449 μM[1]. RK-287107 (0.03-10 μM; 16 hours) causes accumulation of tankyrase and Axin1/2[1]. RK-287107 (0.03-10 μM; 16 hours) also downregulates β-catenin signaling in cultured cells[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.
Cell Proliferation Assay[1]
Cell Line:
Colorectal cancer COLO-320DM, SW403, RKO, HCC2998, HCT-116, and DLD-1 cells
Concentration:
0.01, 0.1, 1, 10 μM
Incubation Time:
12 hours
Result:
Inhibited the growth of APC-mutated (β-catenin-dependent) colorectal cancer COLO-320DM and SW403 cells. The GI50 value of RK-287107 on COLO-320DM is 0.449 μM. Did not inhibit the growth of APC-wild (β-catenin-independent) colorectal cancer cell lines, including RKO, HCT-116, HCC2998 and DLD-1.
Western Blot Analysis[1]
Cell Line:
COLO-320DM cells
Concentration:
0.03, 0.1, 0.33, 1, 3, and 10 μM
Incubation Time:
16 hours
Result:
Downregulation of active β-catenin was observed
体内研究 (In Vivo)
RK-287107 (100 and 300 mg/kg; i.p. administration; once per day; 5-days on/ 2-days off schedule for 2 weeks) inhibits tumor growth in a mouse xenograft model[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.
Animal Model:
6-week-old female NOD.CB17-Prkdcscid/J mice with colorectal cancer COLO-320DM[1]
Dosage:
100 and 300 mg/kg
Administration:
Administration i.p.; once per day; 5-days on/ 2-days off schedule for 2 weeks
Result:
100 and 300 mg/kg resulted in 32.9% and 44.2% TGI, respectively.
分子量
416.46
Formula
C22H26F2N4O2
CAS 号
2171386-10-8
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Mizutani A, et al. RK-287107, a potent and specific tankyrase inhibitor, blocks colorectal cancer cell growth in a preclinical model. Cancer Sci. 2018 Dec;109(12):4003-4014.
OM-1700 is a potent tankyrase inhibitor with IC50s of 127 and 14 nM for tankyrase 1 and tankyrase 2, respectively. OM-1700 reduces cell growth in the colon cancer cell line COLO 320DM (GI50=650 nM)[1].
IC50 & Target[1]
TNKS1
127 nM (IC50)
TNKS2
14 nM (IC50)
体外研究 (In Vitro)
OM-153 shows inhibition (IC50=19 nM) in a cellular (HEK293) WNT/β-catenin signaling reporter assay[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
458.49
Formula
C25H23FN6O2
CAS 号
2406276-78-4
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]. Leenders RGG, et al. Development of a 1,2,4-Triazole-Based Lead Tankyrase Inhibitor: Part II. J Med Chem. 2021;64(24):17936-17949.
OM-1700 is a potent tankyrase inhibitor with IC50s of 127 and 14 nM for tankyrase 1 and tankyrase 2, respectively. OM-1700 reduces cell growth in the colon cancer cell line COLO 320DM (GI50=650 nM)[1].
IC50 & Target[1]
TNKS1
127 nM (IC50)
TNKS2
14 nM (IC50)
体外研究 (In Vitro)
OM-153 shows inhibition (IC50=19 nM) in a cellular (HEK293) WNT/β-catenin signaling reporter assay[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
458.49
Formula
C25H23FN6O2
CAS 号
2406276-78-4
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]. Leenders RGG, et al. Development of a 1,2,4-Triazole-Based Lead Tankyrase Inhibitor: Part II. J Med Chem. 2021;64(24):17936-17949.
OM-1700 is a potent tankyrase inhibitor with IC50s of 127 and 14 nM for tankyrase 1 and tankyrase 2, respectively. OM-1700 reduces cell growth in the colon cancer cell line COLO 320DM (GI50=650 nM)[1].
IC50 & Target[1]
TNKS1
127 nM (IC50)
TNKS2
14 nM (IC50)
体外研究 (In Vitro)
OM-153 shows inhibition (IC50=19 nM) in a cellular (HEK293) WNT/β-catenin signaling reporter assay[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
458.49
Formula
C25H23FN6O2
CAS 号
2406276-78-4
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]. Leenders RGG, et al. Development of a 1,2,4-Triazole-Based Lead Tankyrase Inhibitor: Part II. J Med Chem. 2021;64(24):17936-17949.
Tankyrase-IN-2 (compound 5k) is a potent, selective, and orally active tankyrase inhibitor (IC50s of 10, 7, and 710 nM for TNKS1, TNKS2 as well as PARP1, respectively). Tankyrase-IN-2 has favorable physicochemical profile and pharmacokinetic properties modulating Wnt pathway activity in a colorectal xenograft model[1].
Tankyrase-IN-2 (1-10000 nM; 24 hours) leads to a dose-dependent increase of tankyrase protein abundance with an EC50 of 320 nM in DLD1 cells. This is in the same potency range as the value for axin2 increase (EC50=319 nM)[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
316.30
Formula
C17H14F2N2O2
CAS 号
1588870-36-3
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Buchstaller HP, et al. Discovery and Optimization of 2-Arylquinazolin-4-ones into a Potent and Selective TankyraseInhibitor Modulating Wnt Pathway Activity. J Med Chem. 2019 Aug 5.
XAV-939 is a potent tankyrase inhibitor that targets Wnt/β-catenin signaling. XAV-939 stabilizes axin by inhibiting tankyrase 1 and tankyrase 2 (IC50s of 5 and 2 nM, respectively), thereby stimulating β-catenin degradation. XAV939 binds tightly to the catalytic (PARP) domains of TNKS1 and TNKS2 (Kds of 99 and 93 nM, respectively)[1].
IC50 & Target[6]
TNKS1
5 nM (IC50)
TNKS2
2 nM (IC50)
ARTD1
5500 nM (IC50)
ARTD2
479 nM (IC50)
体外研究 (In Vitro)
XAV939 also binds to recombinant PARP1, although with a significantly lower binding affinity (Kd=1.2 μM). XAV939 (1 μM) strongly inhibis STF activity in SW480 cells, Wnt3a-stimulated STF activity in HEK293 cells, but does not affect CRE, NF-κB or TGF-β luciferase reporters. XAV939 regulates axin levels through tankyrase inhibition in HEK293 cell[1]. XAV939 (0.5 μM, 1.0 μM) reduces DNA-PKcs protein levels 50% of the relative DMSO control in human lymphoblasts[2]. XAV939 induces a second wave of pro-cardiomyocyte gene expression as shown by increased Mesp1 and Isl1expression 2 to 4 days after Wnt inhibition, and by increased Nkx2.5 expression 4 to 6 days after XAV939 addition[3]. XAV-939 (10 nM) has a suppressive effect on elevated MMP-13 levels in both IL-1β-induced SW 1353 cells[4].
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)
XAV-939 (3 mL, 10 nM) has a suppressive effect on elevated MMP-13 levels in the rat OA model[4]. XAV-939 (1 mg/mL, i.p.) ameliorates the psoriasiform skin disease induced by IMQ. XAV-939 results in a significant decrease in the IMQ-induced epidermal hyperplasia (indicated by acanthosis) and dermal inflammatory infiltrates in mice[5].
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
312.31
Formula
C14H11F3N2OS
CAS 号
284028-89-3
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:
DMSO : 25 mg/mL (80.05 mM; ultrasonic and warming and heat to 60°C)
[1]. Huang SM, et al. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature. 2009 Oct 1;461(7264):614-620.
[2]. Dregalla RC, et al. Regulatory roles of tankyrase 1 at telomeres and in DNA repair: suppression of T-SCE and stabilization of DNA-PKcs. Aging (Albany NY). 2010 Oct;2(10):691-708.
[3]. Ao A, et al. DMH1, a Novel BMP Small Molecule Inhibitor, Increases Cardiomyocyte Progenitors and Promotes Cardiac Differentiation in Mouse Embryonic Stem Cells.,PLoS One. 2012;7(7):e41627.
[4]. Zeng L, et al. Chondroprotective effects and multi-target mechanisms of Icariin in IL-1 beta-induced human SW 1353 chondrosarcoma cells and a rat osteoarthritis model. Int Immunopharmacol. 2014 Jan;18(1):175-81.
[5]. Bai J, et al. Epigenetic downregulation of SFRP4 contributes to epidermal hyperplasia in psoriasis. J Immunol. 2015 May 1;194(9):4185-98. doi: 10.4049/jimmunol.1403196. Epub 2015 Mar 30.
[6]. Narwal M, et al. Discovery of tankyrase inhibiting flavones with increased potency and isoenzyme selectivity. J Med Chem. 2013 Oct 24;56(20):7880-9.
[7]. Liu D, et al. Wnt/β-catenin signaling participates in the regulation of lipogenesis in the liver of juvenile turbot (Scophthalmus maximus L.). Comp Biochem Physiol B Biochem Mol Biol. 2016 Jan;191:155-62.
Kinase Assay [1]
To assess the effect of compounds on auto-PARsylation of TNKS, 1 μM GST fusion protein containing the SAM domain and the PARP domain of TNKS2 (a.a. 872-1166) is mixed with 5 μM biotin-NAD+ and 2 μM XAV939 or LDW643 at 30°C for 2.5 hours. Samples are resolved by SDS-PAGE and probed with streptavidin AlexaFluor680. To assess PARsylation of axin, recombinant full-length TNKS2 (expressed/purified as a N-terminal His-tagged protein in bacteria) is incubated with GST-axin 1 (1-280) in the presence of biotin-NAD+ with or without XAV939. The products are resolved and probed with Streptavidin-HRP and imaged using a AlphaInnotech imager. To assess the effect of XAV939, IWR-1-enod, IWR-1-exo, and ABT-888 on auto-PARsylation of TNKS2, His-tagged full-length TNKS2 is incubated with 5 μM biotin-NAD+ and 3 mM of indicated compounds. The products are resolved and probed with Streptavidin-HRP. LC/MS-based high throughput auto-PARsylation assays for PARP1, PARP2, TNKS1, and TNKS2 are setup to monitor the formation of nicotinamide (a by-product of the PARsylation reaction) in the presence of small molecule inhibitors.
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.
Cell Assay [4]
Human SW 1353 chondrosarcoma cells are seeded in 96-well plates (1×104 cells/well) and are treated with Icariin (0, 5, 10, 20, 40, 80, or 100 μM). After 24 h, 20 μL MTT (5 mg/mL in PBS) is added to each well and plates are incubated at 37°C for another 4 h. Supernatants are then removed, and 150 μL DMSO is added to each well. After plates are shaken for 10 min, optical density values measured at 570 nm are recorded using an ELISA reader.
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 [5]
C57BL/6J mice are kept under specific pathogen-free conditions. XAV-939 is injected i.p., at a dose of 1 mg/mL, once a day for seven consecutive days of IMQ treatment (injection volume 100 μL). Control mice are injected with 100 μL 10% DMSO/90% 0.9% NaCl, the solvent for XAV-939. To ameliorate any suffering of mice observed throughout these experimental studies, they are euthanized by CO2 inhalation.
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]. Huang SM, et al. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature. 2009 Oct 1;461(7264):614-620.
[2]. Dregalla RC, et al. Regulatory roles of tankyrase 1 at telomeres and in DNA repair: suppression of T-SCE and stabilization of DNA-PKcs. Aging (Albany NY). 2010 Oct;2(10):691-708.
[3]. Ao A, et al. DMH1, a Novel BMP Small Molecule Inhibitor, Increases Cardiomyocyte Progenitors and Promotes Cardiac Differentiation in Mouse Embryonic Stem Cells.,PLoS One. 2012;7(7):e41627.
[4]. Zeng L, et al. Chondroprotective effects and multi-target mechanisms of Icariin in IL-1 beta-induced human SW 1353 chondrosarcoma cells and a rat osteoarthritis model. Int Immunopharmacol. 2014 Jan;18(1):175-81.
[5]. Bai J, et al. Epigenetic downregulation of SFRP4 contributes to epidermal hyperplasia in psoriasis. J Immunol. 2015 May 1;194(9):4185-98. doi: 10.4049/jimmunol.1403196. Epub 2015 Mar 30.
[6]. Narwal M, et al. Discovery of tankyrase inhibiting flavones with increased potency and isoenzyme selectivity. J Med Chem. 2013 Oct 24;56(20):7880-9.
[7]. Liu D, et al. Wnt/β-catenin signaling participates in the regulation of lipogenesis in the liver of juvenile turbot (Scophthalmus maximus L.). Comp Biochem Physiol B Biochem Mol Biol. 2016 Jan;191:155-62.
