KML 29 |
| Catalog No.GC17385 |
KML 29은 쥐, 마우스, 그리고 인간의 monoacylglycerol lipase (MAGL)에 대한 IC50 값이 각각 43, 15, 5.9nM로 보고되었다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1380424-42-9
Sample solution is provided at 25 µL, 10mM.
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KML 29은 쥐, 마우스, 그리고 인간의 monoacylglycerol lipase (MAGL)에 대한 IC50 값이 각각 43, 15, 5.9nM로 보고되었다.KML29은 체외 및 체내 실험에서 MAGL을 강력하고 선택적으로 억제하고, FAAH에 대한 검출할 수 없는 활성 외에 다른 중추 및 주변 세린 수분해효소에 대한 교차 반응이 최소화되었다[1].
KML 29은 선택적 MAGL 억제제로 작용하여 B16-F10 및 HT-29 세포에 대한 항증식 활동을 보였으며, A431, H1975, OVCAR-3, HCC827, HeLa 및 A549 세포 계에 대해서는 유의미한 영향을 보이지 않았다[2].
KML 29은 낮은 복제 SOD1G93A Amyotrophic lateral sclerosis (ALS) 쥐의 발병, 진행 및 생존을 지연시켰다. 구강 투여된 KML 29은 발병 지연, 증상 개선 및 수명 연장으로 치료적 효과가 있었고, 이는 신경 성장 인자 수준 증가와 염증성 인자 수준 감소와 관련이 있었다[3]. KML 29의 급성 투여는 주로 지방, 뇌 및 척수에서 2-AG 수준을 증가시켰으며 AEA 수준에 아무런 영향을 미치지 않았다. KML 29은 또한 중추신경계 및 주변 장기의 아라킨산 수준을 감소시켰다[4].
References:
[1]. J.W. Chang, M.J. Niphakis, K.M. Lum, A.B. Cognetta 3rd, C. Wang, M.L. Matthews, S. Niessen, M.W. Buczynski, L.H. Parsons, B.F. Cravatt. Highly selective inhibitors of monoacylglycerol lipase bearing a reactive group that is bioisosteric with endocannabinoid substrates. Chem. Biol., 19 (2012), pp. 579-588
[2]. Deng H, Lei Q, Yang N, et al. Discover Monoacylglycerol Lipase Inhibitors by Combination of Fluorogenic Substrate Assay and Activity-Based Protein Profiling[J]. Frontiers in pharmacology, 2022: 3328.
[3]. N. Pasquarelli, M. Engelskirchen, J. Hanselmann, S. Endres, C. Porazik, H. Bayer, E. Buck, M. Karsak, P. Weydt, B. Ferger, A. Witting. Evaluation of monoacylglycerol lipase as a therapeutic target in a transgenic mouse model of ALS. Neuropharmacology, 124 (2017), pp. 157-169
[4]. N Pasquarelli, et al., Comparative biochemical characterization of the monoacylglycerol lipase inhibitor KML29 in brain, spinal cord, liver, spleen, fat and muscle tissue. Neuropharmacology 91, 148-156 (2015).
| 세포 실험 [1]: | |
세포 라인 | A431, H1975, B16-F10, OVCAR-3, HT-29, HCC827, Hela, A549 |
제조 방법 | 세포(각 웰에 약 1,000개)는 100 µl의 배양액으로 96개 웰 판에 심어 24시간 배양한 후 각 웰에 KML29이 포함된 100 µl의 배양액을 추가하여 48시간 더 배양합니다. 그 다음 10 µl의 CCK8 용액을 추가하고 37℃에서 2시간 동안 흡수됩니다. |
반응 조건 | 20 µM KML29， 48 시간 동안 |
응용 분야 | 선택적 MAGL 억제제 KML29은 B16-F10 및 HT-29 세포에 대한 항생장성활성을 보였습니다. |
| 동물 실험 [2]: | |
동물 모형 | MCAO 쥐 |
제조 방법 | 1 mg/kg KML 29은 강력한 공유성 MAGL 억제제로 3일 동안 정맥 주입되었습니다. |
제형 | 정맥 주사, 1mg/kg/d, 3일 동안 |
응용 분야 | KML 29 치료로 인해 낮은 방사선을 보이는 동측면 영역이 감소하였습니다. 약물 치료를 받지 않은 뇌졸중 쥐의 동측면에서 피질과 스트라이엄의 AUC 비율은 각각 0.49 ± 0.04와 0.73 ± 0.02였습니다. KML 29 치료를 통해 피질과 스트라이엄의 해당 비율이 각각 0.72 ± 0.07와 0.88 ± 0.04로 개선되었습니다. |
참고문헌: [1]: Deng H, Lei Q, Yang N, et al. Discover Monoacylglycerol Lipase Inhibitors by Combination of Fluorogenic Substrate Assay and Activity-Based Protein Profiling[J]. Frontiers in pharmacology, 2022: 3328.[2]: Yamasaki T, Hatori A, Zhang Y, Mori W, Kurihara Y, Ogawa M et al Neuroprotective effects of minocycline and KML29, a potent inhibitor of monoacylglycerol lipase, in an experimental stroke model: a small-animal positron emission tomography study.Theranostics. 2021 Sep13;11(19):9492- 9502. | |
| Cas No. | 1380424-42-9 | SDF | |
| Chemical Name | 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(bis(benzo[d][1,3]dioxol-5-yl)(hydroxy)methyl)piperidine-1-carboxylate | ||
| Canonical SMILES | FC(F)(F)C(OC(N1CCC(C(C2=CC3=C(OCO3)C=C2)(O)C4=CC5=C(OCO5)C=C4)CC1)=O)C(F)(F)F | ||
| Formula | C24H21F6NO7 | M.Wt | 549.42 |
| Solubility | DMSO: 2 mg/ml | 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 | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.8201 mL | 9.1005 mL | 18.201 mL |
| 5 mM | 0.364 mL | 1.8201 mL | 3.6402 mL |
| 10 mM | 0.182 mL | 0.9101 mL | 1.8201 mL |
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Quality Control & SDS
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- Purity: >98.50%
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Average Rating: 5 (Based on Reviews and 10 reference(s) in Google Scholar.)
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