Table 2 Overview of studies investigating the effect of G4 ligands on different pancreatic cancer cell lines

4,11-bis(2-aminoethylamino) anthra[2,3-b]furan-5,10-dione (2a),11-bis(2-aminoethylamino) anthra[2,3-b]thiophene-5,10-dione (2b)

PANC-1

72 h

IC₅₀(metabolic activity): 0.26 μM (2a) and 0.9 μM (2b)

x

[169]

5ME

PANC-1

48 h

IC₅₀: 80 μM

x

[122]

Alkyl-modified porphyrins

PANC-1

72 h

IC₅₀(metabolic activity): ~15 nM

x

[142]

Azidothymidine (AZT)

MIA PaCa-2

4 and 7 days

IC₅₀: >200 μM

x

[162]

BMSG-SH3

MIA PaCa-2

n.a.

50% decreased tumor growth of MIA-Pa-Ca2 xenografts

No in vitro cyto-toxicity assay done

x

[168]

C14

PANC-1

n.a.

IC₅₀: ~10 nM when irradiated with halogen light

x

[141]

C-2028

PANC-1, MIA PaCa-2, BXpC-3, AsPC-1, Capan-2

72 h

IC₅₀ for all cell lines < 100 nm

About 80% reduced Panc-1 xenograft growth in vivo

x

[170]

CM03

MIA PaCa-2,

PANC-1

96 h

IC₅₀: 7 nM (MIA), 18 nM (PANC-1), reduced tumor growth by ~ 73%

x

[171,172,173]

Copper(ii) l/d-valine-(1,10-phen) complexes

(complex 1a, 1b)

BxPC3, AsPC1

72 h

IC₅₀: ~2 μM for both complexes in both cell lines

x

[174]

CX-3543 (Quarfloxin)

MIA PaCa-2

n.a.

>50% reduced tumor growth of MIA PaCa-2 xenografts

x

x

[129]

CX-5461

Gemcitabine-resistant MIA PaCa-2 (GemMIA-R3) and normal MIA-PA-Ca2

96 h

GI₅₀: 90.3 nM (GemMIA-R3), 88.7 nM (MIA-Pa-Ca2)

x

[175]

MM41

MIA PaCa-2,

PANC-1

96 h

IC₅₀: 11 nM (MIA), 3 nM (PANC-1), ~80% reduced growth of MIA PaCa-2 xenografts in vivo

x

[163, 171]

Naphthalene diimide ligands

(compounds 3d, 3h)

MIA PaCa-2

96 h

IC₅₀: 10 nM for both compounds

x

-

[45]

Naphthalene diimide isomer ligands (compounds 2-5)

MIA PaCa-2

PANC-1

96 h

IC₅₀: 5-130 nM (MIA PaCa-2), 2 nM-1.5 μM (PANC-1)

-

[176]

Nitidine

AsPC-1, BxPC-3, MIA PaCa-2, PANC-1

72 h

IC₅₀: 6.1 μM (AsPC-1), 5.2 μM (BxPC-3), 13.4 μM (MIA PaCa-2), 35.3 μM (PANC-1)

x

[160]

Octaacetyl

Panc-1_h, MIA PaCa-2_h

24-72 h

IC₅₀: 65, 40, 36 μM for PANC-1 (24, 48, 72 h) and 62, 38, 33 μM for MIA PaCa-2

Reduced tumor growth in vivo

x

[164]

RHPS4

PAXF 736

15 days colony forming assay

IC₅₀: 0.44 μM

x

[177]

SOP1812

MIA PaCa-2, PANC-1, Capan-1, BXPC-3

96 h

GI₅₀: 1.3 nM (MIA PaCa-2), 5.9 nM (Capan-1)

Significantly reduced MIA PaCa-2 xenograft growth in vivo

x

[173]

Telomestatin

MIA PaCa-2

48 h

IC₅₀: 0.5 μM

x

[178]

Tetrakis

PANC-1, MIA PaCa-2

24-72 h

IC₅₀: 60, 31, 25 μM (PANC-1) and 65, 36, 30 μM (MIA PaCa-2) for 24, 48, 72 h

Reduced tumor growth in vivo

x

[164]

Tetrasubstituted naphthalene diimide ligands

PANC-1, MIA PaCa-2_, HPAC_, BxPc-3

96 h

IC₅₀: 0.1-0.2 μM (PANC-1, MIA PaCa-2_, HPAC), 1.5 μM (BxPc-3)

x

x

[179]

TMPyP4

MIA PaCa-2, PANC-1

48 h, 4 and 7 days

IC₅₀: 21.9 μM (MIA PaCa-2

, 4 days), 50 μM (PANC1, 7 days), 50 μM (MIA PaCa-2, 48 h), ~20 μM (PANC-1, 48 h). ~30% KRAS inhibition after 12 and 24 h

x

[122, 142, 154, 162, 178]