Table 2 SK1 and SK2 inhibitors used in PDAC study

PF-543 derivatives (Compounds 5

and 10)

Inhibition of SK1, activation of cleaved caspase 3 and PARP and apoptosis, PP2A activation

In vitro: MIA PaCa2, PANC-1 and H6C7

(-)

[152]

SKI-II

Increased ceramide production by inhibition of SK1 and induced apoptosis through JNK activation

In vitro: MIA PACa2 and PANC-1

(-)

[153]

FTY720

Enhanced effect of gemcitabine, increased apoptosis, suppressed NF-kB and STAT3 pathway, Activation of PP2A, Inhibition of epithelial-mesenchymal transition

In vitro: BxPC-3, AsPC-1, MIA PaCa-2 and PANC-1 and PAN 02 cell lines

S1PR1

[74]

In vivo: NOD.CB17-Prkdcscid/J mice and C57Bl/6 mice

RB005

Inhibition of PDAC proliferation and migration through inhibition of SK1

In vitro: PANC-1, Capan-1 and MIA PaCa-2

(-)

[64]

PF543

Inhibition of PDAC proliferation and migration through inhibition of SK1

In vitro: PANC-1, Capan-1 and MIA PaCa-2

(-)

[64]

SK2 inhibitors used in PDAC.

ABC294640

Inhibition of SK2 and HDAC1/2 to downregulates c-MYC and RRM2 gene in pancreatic cancer

In vitro: MIA PaCa-2, BxPC-1, Panc-1

(-)

[114]

ABC294640

Clinical trial: human PADC patients

(-)

[155]

ABC294735

Inhibition of SK1/2 with activation of caspase3/7 to induce apoptosis along with suppression of ERK phosphorylation

Activation of caspase3/7 leading to apoptosis together with suppression of ERK phosphorylation by SK1/2 inhibition

In vitro: BxPC-3

(-)

[154]

In vivo: SCID mice

PF543 derivative (Compound 10)

Inhibition of SK2 and AKT/ERK pathway to induce apoptosis, Activation of PP2A

In vitro: MIA PaCa-2, Panc-1, H6C7

(-)

[151]