ABC99 |
Katalog-Nr.GC42669
One-Click Copy Product Info
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ABC99 ist ein N-Hydroxyhydantoin (NHH)-Carbamat, das selektiv das Wnt-deacylierende Enzym NOTUM hemmt (IC50=13 nM). ABC99 bewahrt die Wnt3A-Signalisierung in Gegenwart von NOTUM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2331255-53-7
Sample solution is provided at 25 µL, 10mM.
ABC99 is an N-hydroxyhydantoin (NHH)-carbamate-based, irreversible and selective inhibitor of Wnt-deacylating enzyme NOTUM[1]. NOTUM is a secreted serine hydrolase that negatively modulates Wnt/β-catenin signaling by removing the essential palmitoleate moiety from Wnt proteins[2]. ABC99 is usually used in models of osteoporosis, colorectal cancer and neurodegenerative diseases where Wnt signaling is insufficient[3][4].
In vitro, ABC99 (2µg/mL; 7–14 days) suppressed odontoblastic differentiation of human stem cells from apical papilla (hSCAPs), reduced ALP activity, blocked mineralized nodule formation, and decreased DSPP, DMP1 and ALP mRNA levels[5]. ABC99 (50nM and 500nM; 14 days) significantly reversed the inhibition of osteogenic differentiation of hPDLSCs by recombinant human NOTUM, restored ALP activity and calcium nodule formation, and increased the protein/mRNA levels of Osterix, OCN and Runx2[6].
In vivo, ABC99 (10mg/kg/day; p.o.; 4 weeks) almost completely prevented liver metastasis and lymph-node metastasis, reduced primary tumor weight, and significantly inhibited Ki67⁺ cell proliferation in orthotopic colorectal cancer mice[7].
References:
[1] Suciu RM, Cognetta AB 3rd, Potter ZE, Cravatt BF. Selective Irreversible Inhibitors of the Wnt-Deacylating Enzyme NOTUM Developed by Activity-Based Protein Profiling. ACS Med Chem Lett. 2018;9(6):563-568.
[2] Bayle ED, Svensson F, Atkinson BN, et al. Carboxylesterase Notum Is a Druggable Target to Modulate Wnt Signaling. J Med Chem. 2021;64(8):4289-4311.
[3] Zhao Y, Jolly S, Benvegnu S, Jones EY, Fish PV. Small-molecule inhibitors of carboxylesterase Notum. Future Med Chem. 2021;13(11):1001-1015.
[4] Larrick JW, Mendelsohn AR. Roads to the Fountain of Youth? Rejuvenating Intestinal Stem Cells. Rejuvenation Res. 2019;22(4):342-347.
[5] Zhao Q, Ren H, Wang N, Yuan X, Zhao Y, Wen Q. NOTUM plays a bidirectionally modulatory role in the odontoblastic differentiation of human stem cells from the apical papilla through the WNT/β-catenin signaling pathway. Arch Oral Biol. 2024;160:105896.
[6] Yang P, Li C, Kou Y, et al. Notum suppresses the osteogenic differentiation of periodontal ligament stem cells through the Wnt/Beta catenin signaling pathway. Arch Oral Biol. 2021;130:105211.
[7] Tian Y, Wang X, Cramer Z, et al. APC and P53 mutations synergise to create a therapeutic vulnerability to NOTUM inhibition in advanced colorectal cancer. Gut. 2023;72(12):2294-2306.
| Cell experiment [1]: | |
Cell lines | Human stem cells from the apical papilla (hSCAPs) |
Preparation Method | Human stem cells from the apical papilla (hSCAPs) were recovered and cultured in a cell culture incubator under the conditions of 37°C with 5% CO2 (v/v). The culture medium was refreshed every 3 days. The normal proliferation medium (PM) contained α-MEM, 10% fetal bovine serum, and 1% penicillin. When cells reached 80% confluency, odontoblastic medium (OM) contained α-MEM, 10% fetal bovine serum, 50mg/L L-Ascorbic acid, 5mmol/L sodium β-phosphoglycerate, and 10nmol/L dexamethasone, was used to induce odontoblastic differentiation. To down-regulate the extracellular NOTUM level, ABC99, a small molecule inhibitor of NOTUM, was added to the OM medium at 2ug/ml. Cells were collected on odontoblastic induction day 3, 7, and 14. Alkaline phosphatase (ALP) staining, Alizarin red (ARS) staining and qRT-PCR were performed according to the manufacturer’s Instructions. |
Reaction Conditions | 2µg/mL; 7–14 days |
Applications | ABC99 suppressed odontoblastic differentiation of human stem cells from apical papilla (hSCAPs), reduced ALP activity, blocked mineralized nodule formation, and decreased DSPP, DMP1 and ALP mRNA levels. |
| Animal experiment [2]: | |
Animal models | C57BL/6J mice |
Preparation Method | 8-week-old, specific-pathogen-free C57BL/6J mice were kept in an air-conditioned room at a temperature of 23±1℃, a relative humidity of 50–70%, and a 12h light/dark cycle. APKS tumor organoids were orthostatic implanted into the colonic mucosa of C57BL/6J mice under endoscopic guidance to establish an in situ colorectal cancer model. Mice were treated with ABC99(10mg/kg/day; p.o.) or vehicle (corn oil) control after 4 weeks of engraftment and tumour growth. Mice are treated for indicated number of weeks (week 0-4 weeks post-implantation) (n=7 mice). Tumour weight, number of macrometastases in the liver and number of lymph node metastases in mice were qualified. Bioluminescent imaging (BLI) and Kaplan–Meier survival analysis were performed to monitor tumor burden and compare survival. |
Dosage form | 10mg/kg/day; p.o.; 4 weeks |
Applications | ABC99 almost completely prevented liver metastasis and lymph-node metastasis, reduced primary tumor weight in orthotopic colorectal cancer mice. |
References: | |
| Cas No. | 2331255-53-7 | SDF | |
| Chemical Name | 7-(4-chlorobenzyl)-1,3-dioxohexahydroimidazo[1,5-a]pyrazin-2(3H)-yl-2,3-dihydro-4H-benzo[b][1,4]oxazine-4-carboxylate | ||
| Canonical SMILES | ClC1=CC=C(CN2CC(C(N(OC(N3C(C=CC=C4)=C4OCC3)=O)C5=O)=O)N5CC2)C=C1 | ||
| Formula | C22H21ClN4O5 | M.Wt | 456.9 |
| Löslichkeit | 1mg/mL in Chloroform, 1mg/mL in acetonitrile, 1mg/mL in methyl acetate | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1887 mL | 10.9433 mL | 21.8866 mL |
| 5 mM | 437.7 μL | 2.1887 mL | 4.3773 mL |
| 10 mM | 218.9 μL | 1.0943 mL | 2.1887 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >95.00% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 37 reference(s) in Google Scholar.)