In vitro: The pro-survival protein myeloid cell leukemia 1 (MCL1) is over expressed in many cancers. S63845 is a small molecule that specifically binds with high affinity to the BH3-binding groove of MCL1. S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma, leukaemia and lymphoma cells, by activating the BAX/BAK-dependent mitochondrial apoptotic pathway. The activity of S63845 is next evaluated in a panel of eight AML cell lines: all lines are sensitive to S63845 (IC50=4-233 nM). 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.
Cancers (Basel). 2021 May 12;13(10):2310.
Unmasking BCL-2 Addiction in Synovial Sarcoma by Overcoming Low NOXA
S63845 purchased from AbMole
Mol Carcinog. 2020 Nov;59(11):1256-1268.
Mcl-1 targeting strategies unlock the proapoptotic potential of TRAIL in melanoma cells
S63845 purchased from AbMole
|Source||MOL CARCINOGEN 2020. Figure 5. S63845 (Abmole Bioscience, USA)|
|Cell Lines||Origin of human melanoma cell lines|
|Incubation Time||24 hours|
|Results||When applied alone, S63845 resulted in 15% apoptosis induction and reduction of viable cells to 60%. The proapoptotic Bcl-2 proteins Bax and Bak were strongly activated by S63845 (44%).|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
|Solubility||10mM in DMSO|
|Storage||powder, at 4°C, protect from light, dry|
S63845, an MCL-1 Selective BH3 Mimetic: Another Arrow in Our Quiver.
Letai A, et al. Cancer Cell. 2016 Dec 12;30(6):834-835. PMID: 27960083.
The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models.
Kotschy A, et al. Nature. 2016 Oct 27;538(7626):477-482. PMID: 27760111.
|Related Bcl-2 Products|
AZD-5991 Racemate is a Mcl-1 inhibitor with an IC50 of <3 nM in FRET assay.
|Bax inhibitor peptide V5
Bax inhibitor peptide V5 is a Bax-mediated apoptosis inhibitor.
Marinopyrrole A (Maritoclax) is a novel and specific Mcl-1 inhibitor with an IC50 value of 10.1 μM.
MIK665 is an inhibitor of induced myeloid leukemia cell differentiation protein (Mcl-1; Bcl2-L-3).
BDA-366 is a small molecule antagonist that specifically binds the BCL2 BH4 domain, and has the ability to convert anti-apoptotic BCL2 into a pro-apoptotic death molecule.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2020 AbMole BioScience. All Rights Reserved.