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
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Source | MOL CARCINOGEN 2020. Figure 5. S63845 (Abmole Bioscience, USA) |
| Method | Cell culture | |
| Cell Lines | Origin of human melanoma cell lines | |
| Concentrations | 5 µM | |
| 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%). |
| Molecular Weight | 829.26 |
| Formula | C39H37ClF4N6O6S |
| CAS Number | 1799633-27-4 |
| Solubility (25°C) | 10mM in DMSO |
| Storage | powder, at 4°C, protect from light, dry |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| 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.
| Related Bcl-2 Products |
|---|
| BAD (103-127) (human)
BAD (103-127) (human), the 25-mer Bad peptide, is derived from the BH3 domain of BAD, can antagonize the function of Bcl-xL. |
| Bim BH3, Peptide IV
Bim BH3, Peptide IV is a 26-residue peptide from BH3-only protein Bim, which belongs to the pro-apoptotic group of the Bcl-2 family of proteins. |
| Bax inhibitor peptide, negative control
Bax inhibitor peptide, negative control is a inhibitor of Bax. |
| Bad BH3 (mouse)
Bad BH3 (mouse) is a biological active peptide. |
| Bid BH3 (80-99)
Bid BH3 (80-99) is a biological active peptide. |
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