| Identification | Back Directory | [Name]
S63845 | [CAS]
1799633-27-4 | [Synonyms]
S63845
CS-2477
CS-2485
S 63845;S-63845
(2R)-2-(5-(3-chloro-2-methyl-4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl)-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yloxy)-3-(2-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)methoxy)phenyl)propanoic acid
(R)-2-((5-(3-chloro-2-methyl-4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl)-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl)oxy)-3-(2-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)methoxy)phenyl)propanoic acid
Benzenepropanoic acid, α-[[(5S)-5-[3-chloro-2-methyl-4-[2-(4-methyl-1-piperazinyl)ethoxy]phenyl]-6-(5-fluoro-2-furanyl)thieno[2,3-d]pyrimidin-4-yl]oxy]-2-[[1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl]methoxy]-, (αR)- | [Molecular Formula]
C39H37ClF4N6O6S | [MDL Number]
MFCD31382374 | [MOL File]
1799633-27-4.mol | [Molecular Weight]
829.26 |
| Chemical Properties | Back Directory | [Boiling point ]
852.6±65.0 °C(Predicted) | [density ]
1.46±0.1 g/cm3(Predicted) | [storage temp. ]
4°C, protect from light, stored under nitrogen | [solubility ]
insoluble in H2O; ≥20 mg/mL in MeOH; ≥41.45 mg/mL in DMSO | [form ]
A crystalline solid | [pka]
2.54±0.11(Predicted) | [color ]
White to yellow | [InChIKey]
ZFBHXVOCZBPADE-JZEPPUFONA-N | [SMILES]
C1C=C(OCC2=CC=NN2CC(F)(F)F)C(C[C@@H](OC2C3C(C4C=CC(OCCN5CCN(C)CC5)=C(Cl)C=4C)=C(C4=CC=C(F)O4)SC=3N=CN=2)C(=O)O)=CC=1 |&1:17,r| |
| Hazard Information | Back Directory | [Description]
S63845 is an inhibitor of myeloid cell leukemia 1 (Mcl-1; Ki = 0.19 nM), a pro-survival protein that is overexpressed in many cancers.1 It induces cell death in multiple myeloma, leukemia, and lymphoma cell lines (IC50s = <0.1-282 nM) via mitochondrial apoptosis. S63845 acts synergistically with trametinib (Item No. 16292), lapatinib (Item No. 11493), PLX4032 (Item No. 10618), and erlotinib (Item No. 10483) to reduce proliferation of SK-MEL-2, BT474, A2058, and PC9 cells, respectively. S63845 (6.25-25 mg/kg) reduces tumor volume in an MV4-11 acute myeloid leukemia mouse xenograft model in a dose-dependent manner. | [Uses]
S-63845 is used in killing senescent cells and treating senescence-associated diseases or disorders using a combination of a BCL inhibitor and an MCL-1 inhibitor.Potent and selective MCL1 inhibitor | [in vivo]
S63845 shows potent anti-tumour activity with an acceptable safety margin as a single agent in several cancers. Intravenously injected (i.v.) S63845 exerts dose-dependent anti-tumour activity in human multiple myeloma (H929 and AMO1) xenografts in immunocompromised mice, with maximal tumour growth inhibition of 114% in the AMO1 model and 103% in the H929 model. At 25 mg/kg, S63845 induces complete regression in 7 out of 8 of the mice at 100 days after treatment in the AMO1 model[1]. | [IC 50]
MCL1: 0.19 nM (Kd) | [References]
[1] ANDRáS KOTSCHY. The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models[J]. Nature, 2016, 538 7626: 477-482. DOI: 10.1038/nature19830 |
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