186348-23-2 Usage
Biological Activity
bay-598 is a aminopyrazoline-based in-vivo probe for smyd2.smyd2 is a catalytic set domain containing protein methyltransferase to monomethylate lysine residues on histone and nonhistone proteins. the overexpression of smyd2 has been found in cancer cell lines and also in various cancer patients.
in vitro
previous data suggest that bay-598 is a peptide-competitive, sam-uncompetitive inhibitor of smyd2 methyltransferase activity, binding to the smyd2 sam substrate complex. bay-598 was tested on a panel of 32 additional methyltransferases, and the results showed that bay-598 displayed >100-fold selectivity for smyd2, with very weak activity for the closest related methyltransferase smyd3. though bay-598 proved to be active for both smyd2 inhibition and par1 antagonism, there was still a greater than 50-fold selectivity for smyd2 relative to par1 [1].
in vivo
in animal study, mice bearing subcutaneous tumor xenografts were orally treated with 10, 30, 70, or 100 mg/kg bay-598 once daily for 3 days. results showed that bay-598 could significantly reduce the methylation with doses starting from 30 mg/kg, with most significant effects in the 100 mg/kg group. treatment with 10 mg/kg bay-598 showed no significant effect on the methylation level, although the exposure at 10 mg/kg was close to the cellular ic50 for about 9 h, indicating an even higher exposure as the ic50 to achieve in-vivo effects [1].
IC 50
27 nm
references
[1] eggert e,hillig rc,koehr s,et al. discovery and characterization of a highly potent and selective aminopyrazoline-based in vivo probe (bay-598) for the protein lysine methyltransferase smyd2. j med chem.2016 may 26;59(10):4578-600.
Check Digit Verification of cas no
The CAS Registry Mumber 186348-23-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,8,6,3,4 and 8 respectively; the second part has 2 digits, 2 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 186348-23:
(8*1)+(7*8)+(6*6)+(5*3)+(4*4)+(3*8)+(2*2)+(1*3)=162
162 % 10 = 2
So 186348-23-2 is a valid CAS Registry Number.
186348-23-2Relevant academic research and scientific papers
The synthesis of novel taxoids for oral administration
Jing, Yun-Rong,Zhou, Wei,Li, Wan-Liang,Zhao, Lin-Xiang,Wang, Yong-Feng
, p. 194 - 203 (2014/01/17)
A group of novel taxoids, with modifications at C-7, C-10, C-3′ and C-14 positions of paclitaxel, was synthesized in order to improve their biological profile by decreasing their affinity with P-glycoprotein (P-gp) and increasing cellular permeability. Most of the new taxoids demonstrated the similar potent cytotoxic activities in MCF-7 human tumor cell line as paclitaxel in vitro. In the permeability assay with monolayers of Caco-2 cells, most of the compounds demonstrated an increased trans-cellular transport in A-to-B direction in comparison with paclitaxel. Among them the compounds T-13, T-15 and T-26 showed the highest permeability, and with efflux ratios better than that of ortataxel. The interaction of the compounds T-13 and T-26 with P-gp was evaluated using Madin-Darby canine kidney (MDCK)-multidrug resistance-1(MDR1) and MDCK-wild-type (WT). The results indicated that T-13 and T-26 were poor substrates for P-gp and possessed inhibiting effects of P-gp mediated efflux. It was thus clear that simultaneous modifications at the C-7, C-10 and C-3′ positions of paclitaxel significantly impaired its interactions with P-gp and interfered with P-gp mediated efflux.
Syntheses and structure-activity relationships of taxoids derived from 14β-hydroxy-10-deacetylbaccatin III
Ojima, Iwao,Slater, John C.,Kuduk, Scott D.,Takeuchi, Craig S.,Gimi, Rayomand H.,Sun, Chung-Ming,Park, Young Hoon,Pera, Paula,Veith, Jean M.,Bernacki, Ralph J.
, p. 267 - 278 (2007/10/03)
A series of new taxoids derived from 14β-hydroxy-10-deacetylbaccatin III was synthesized by means of the β-lactam synthon method. Most of the new taxoids thus synthesized possess excellent cytotoxicity against human ovarian (A121), non-small-cell lung (A5
