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Target nature : CDK5/p25
CAS n° : 10540-29-1
Mecanism of action : inhibition of protein-protein interaction
Physico-chemical properties : WHITE POWDER Experimental Melting Point: 97-98 °C Sigma-Aldrich SIAL-06734 Experimental LogP: 6.342 LabNetwork (old) LN00198968 Experimental Solubility: 10 mM in DMSO MedChem Express HY-13757A DMSO 100 mg/mL; Water <1 mg/mL MedChem Express HY-13757A Methanol: soluble 50 mg/mL, clear, colorless
Probe availability : commercial
Princeps reference : Corbel C. et al. 2015. Tamoxifen Inhibits CDK5 Kinase Activity by Interacting with p35/p25 and Modulates the Pattern of Tau Phosphorylation. Chemistry & Biology 22 (4), 472-482
More bibliography : Lukasik P et al. 2021. Inhibitors of Cyclin-Dependent Kinases: Types and Their Mechanism of Action. Int J Mol Sci. 2021 Mar 10;22(6):2806. doi: 10.3390/ijms22062806. Oner M et al. 2019. Future Aspects of CDK5 in Prostate Cancer: From Pathogenesis to Therapeutic Implications. Int J Mol Sci. 2019 Aug 9;20(16):3881. doi: 10.3390/ijms20163881. Rohlff, C., et al. 1998. Prostate 37, 51. Couldwell, W.J., et al. 1994. FEBS Lett. 345, 43. Baltuch, G.H., et al. 1993. Neurosurgery 33, 495. Powis, G. 1991. Trends Pharmacol. Sci. 12, 188. Issandou, M., et al. 1990. Cancer Res. 50, 5845. O'Brian, C.A., et al. 1985. Cancer Res. 45, 2462.
Other available information on the probe : Putative repositioning of tamoxifen: Inhibition of protein-protein interaction (CDK5/p25) and modulation of Tau phosphorylation pattern
Other information on the target : Interaction between CDK5 and p25
Selectivity profile : Micromolar efficiencies: CDK5/p25 and CDK5/p35 (IC50 against CDK5/p25= 4µM) ; Acyl-coenzyme A:cholesterol acyltransferase (ACAT); protein kinase C (PKC, the level of PKC inhibition by TMX varies from 25 mM to 100 mM); calmodulin (CaM)-dependent enzymes (Calmodulin); Nanomolar efficiencies: estrogen receptor (ER, Kd = 1 nM); microsomal anti-estrogen binding site (AEBS). See also: de Medina, P., Favre, G., and Poirot, M. (2004). Multiple targeting by the antitumor drug tamoxifen: a structure-activity study. Curr. Med. Chem. Anticancer Agents 4, 491-508.
In vivo data : Tamoxifen was never tested on CDK5/p25-related mouse model. From Maani, N., Sabha, N., Rezai, K. et al. Tamoxifen therapy in a murine model of myotubular myopathy. Nat Commun 9, 4849 (2018). "Tamoxifen (TAM) was given at either a low (3 mg/kg) or high (40 mg/kg) dose, with low-dose modeling human pediatric dosing and high dose matching what is used for Cre-lox recombination in mice."
In vitro data : From Corbel et al. 2015: in the presence of 100 µM glutamate and 20 µM MG132, the addition of increasing concentrations of tamoxifen (5-15µM) decreases the phosphorylation of tau (pSer214) in primary neuronal cultures.
Toxicity : Induces apoptosis in human malignant glioma cell lines and inhibits prostate cancer cell growth by induction of p21 protein. WARNING: This product is known to cause reproductive toxicity with developmental effects. Risk Classification: Acute Tox. 4 Oral - Aquatic Acute 1 - Aquatic Chronic 1 - Carc. 1B - Repr. 1B R: 22-45-60-61-64 Harmful if swallowed. May cause cancer. May impair fertility. May cause harm to the unborn child. May cause harm to breastfed babies. S: 36/37/39-45 Wear suitable protective clothing, gloves and eye/face protection. In case of accident or if you feel unwell, seek medical advice immediately (show the label where possible).
Chaine SMILES : CC/C(=C(c1ccccc1)/c2ccc(OCCN(C)C)cc2)c3ccccc3
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