PAC-1 is a procaspase-activating compound; activates procaspase-3 to produce caspase-3 (EC50 = 0.22 μM). PAC-1 enhances the activity of procaspase-3 in vitro and induces apoptotic death in cancer cells in culture and in mouse xenograft models. Signaling through the neuropeptide GPCR PAC(1) induces neuritogenesis via a single linear cAMP- and ERK-dependent pathway using a novel cAMP sensor. The data presented herein further bolster the hypothesis that PAC-1 induces apoptosis in cancer cells through the direct activation of procaspase-3, has implications for the design and discovery of next-generation procaspase-3 activating compounds, and sheds light on the anti-apoptotic role of cellular zinc.
 |
Source | Exp Hematol (2015). Figure 2.PAC-1 |
| Method | flow cytometry | |
| Cell Lines | MM cell lines | |
| Concentrations | 3 and 10 μmol/L | |
| Incubation Time | 24 hours | |
| Results | Both MM.1S and U266 cells demonstrated a time-dependent decrease in cell viability. |
| Cell Experiment | |
|---|---|
| Cell lines | U-937, HL-60, CRL-1872, ACHN, NCI-H226, Hs888Lu, Hs578Bst, MCF-10A, SK-MEL-5, BT-20, MDA-MB-231, UACC-62, SK-N-SH, B16-F10 , Hs 578t and PC-12 |
| Preparation method | Determination of IC50 values in various cell lines. Various concentrations of etoposide or PAC-1 were added to cells and incubated for 24 h and 72 h for etoposide and PAC-1, respectively. Cell death was quantified by the addition of MTS/PMS CellTiter 96 Cell Proliferation Assay reagent (Promega). The plates were incubated at 37 1C for approximately 1 h (until the colored product formed), and the absorbance was measured at 490 nm. |
| Concentrations | 0~20 µM |
| Incubation time | 24 h and 72 h |
| Animal Experiment | |
|---|---|
| Animal models | nude mice bearing NCI-H226 xenograft model |
| Formulation | mixture of 24:1 vegetable oil/DMSO |
| Dosages | 50 and 100 mg/kg once a day for 21 d |
| Administration | oral gavage |
| Molecular Weight | 392.5 |
| Formula | C23H28N4O2 |
| CAS Number | 315183-21-2 |
| Solubility (25°C) | DMSO 48 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| 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 Caspase Products |
|---|
| TC11
TC11 is a phenylphthalimide derivative and an activator of caspase-9 and CDK1, as well as a degrader of MCL1.TC11 is structurally related to immunomodulatory active molecules. During prolonged mitotic blockade, TC11 induces MCL1 degradation and leads to apoptotic death. |
| Ac-Ile-Glu-Thr-Asp-pNA
Ac-Ile-Glu-Thr-Asp-pNA is a substrate for caspase-8. |
| Z-DEVD-AFC
Z-DEVD-AFC is a cell-permeant substrate for caspase-3, which causes a shift in fluorescence uponcleavage of the AFC fluorophore. |
| Ac-IETD-AFC
Ac-IETD-AFC is a fluorogenic substrate of caspase-8, caspase-3, caspase-10, and granzyme B. |
| Z-VDVAD-FMK
Z-VDVAD-FMK is a special inhibitor of caspase-2. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
