S63845
S63845 Basic information
- Product Name:
- S63845
- Synonyms:
-
- (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
- (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
- 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)-
- S63845
- S 63845;S-63845
- CS-2477
- CS-2485
- S63845 TFA
- CAS:
- 1799633-27-4
- MF:
- C39H37ClF4N6O6S
- MW:
- 829.26
- Product Categories:
-
- API
- Mol File:
- 1799633-27-4.mol
S63845 Chemical Properties
- 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|
S63845 Usage And Synthesis
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. 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 , lapatinib , PLX4032 , and erlotinib 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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