Table 2 Inhibitors of STAT3 in pre-clinical studies

NTD

ST3-H2A2

(Peptide)

The IC50 of prostate cancer cells (LNCaP, PC3, DU145) were less than 5 μM.

NA

[181]

CCD

MS3–6 (Ab)

NA

NA

[182]

DBD

InS3-54A18 (SM)

Lung cancer cells (A549, H1299) and breast cancer cells (MDA-MB-231, MDA-MB-468), 3.2–4.7 μM.

A549 xenograft, 200 mg/kg, oral dosing 2–3 times a week for 4 weeks.

[183]

Galiellalactone (SM)

Docetaxel-resistant DU145 cells spheres (6.2 μM), docetaxel-sensitive DU145 spheres (10.1 μM)

DU145 xenograft, 1 mg/kg and 3 mg/kg, i.p injection QD for 3 weeks.

[184, 185]

SG-1709 (SM)

MDA–MB-468 (10.14 μM)

NA

[186]

SG-1721 (SM)

MDA–MB-468 (6.9 μM)

0.5 mg/kg, i.p 3 times/week for 20 days

[186]

GPA512 (SM)

DU145 (4.81 mM)

Orally, DU145 bearing nude mice, 40 mg/kg, QD five times/week.

[187]

HJC0152 (SM)

AGS and MKN45, less than 10 μM.

MKN45 bearing BALB/c nude mice, 7.5 mg/kg HJC0152 dissolved in 100 μL PBS i.p twice weekly for 21 days.

[188]

Silibinin (SM)

MDA-MB-231, 200―250 μM.

Female SKH-1 hairless mice, 1% (w/w) silibinin fed in diet, less tumor numbers in UVB caused tumorigenesis.

[189, 190]

HO-3876 (SM)

NA

A2780 bearing BALB/c nude mice, HO-3867 was mixed with the animal feed (Harlan Teklad) at 3 different levels (25, 50, and 100 ppm).

[191]

LC28 (SM)

H1299 (8.1 ± 4.1 μM), SKOV3 (3.7 ± 0.7 μM), SKOV3/DDP (14.7 ± 2.4 μM)

NA

[192]

MMPP (SM)

NCI-H460 (1.95 μg/mL), NSCLC (12.3 μg/mL)

NCI-H460 xenograft model and PDX model, 2.5–5 mg/kg, i.p. twice a week for 3 weeks.

[193]

Bruceantinol (SM)

HCT116 (18.7 ± 3.3 nM), HCT116 p53^−/−(18.7 ± 3.3 nM), HCA-7 (23.6 ± 4.8 nM), H630 (43.2 ± 5.9 nM), H630R1 (49.7 ± 4.6 nM)

HCT116 tumor bearing xenografts, 2 mg/kg and 4 mg/kg; i.p. thrice per week.

[194]

DBD-1-9R (Peptide)

U266 cells, 270 nM

NA

[195]

15-mer duplex ODN (Oligonucleotides)

SCCHN Cell, less than 25 μM

NA

[196]

CPA-7

(Platinum-based)

RM-9 cells, 20 μM

0.75 mg/kg, 1.5 mg/kg, RM-9 tumor bearing C57BL/6 J mice, tail vein injection every three days

[197]

Linker domain

BPMB (SM)

NA

NA

[198]

SH2 domain

Periplogenin (SM)

KYSE30 (1.707 ± 0.275 μM);

KYSE70 (2.898 ± 0.959 μM);

KYSE450 (1.201 ± 0.167 μM).

ESCC patient-derived xenograft, i.p BID, 8 mg/kg and 16 mg/kg.

[33]

ODZ10117 (SM)

NA

GSC528 tumor bearing BALB/c nu/nu nude mice, i.p injection, 0.1 mg/kg or 1 mg/kg, six times per week; U87-MG tumor bearing BALB/c nu/nu nude mice, BID for 2 weeks.

[199]

N4 (SM)

CAPAN-2, PANC-1, MIAPACA-2, BXPC-3, HPAC, CFPAC-1, less than 4 μM.

PANC-1 cells tumor bearing BALB/c-nude mice, i.p QD for 20 days.

[200]

SD-36 (SM)

MOLM-16 (35 nM), DEL (1.48 μM), Karpas (0.98 μM), KI-JK (0.18 μM), SU-DHL-1 (0.25 μM)

SCID mice bearing MOLM-16 tumors; 100 mg/kg weekly; 50 mg/kg 3 times per week; 100 mg/kg twice a week for 3 weeks.

[201]

Stattic (SM)

OSC-19 (3.481 ± 0.953 μM), UM-SCC-17B (2.562 ± 0.409 μM), Cal33 (2.282 ± 0.423 μM), UM-SCC-22B (2.648 ± 0.542 μM)

UM-SCC-17B tumor-bearing mice, 50 mg/kg, orally gavage, 5 days a week for 4 weeks.

[202]

S3I-201 (SM)

LNCaP (300 μM)

Human breast (MDA-MB-231) tumor-bearing mice were given S3I-201 (5 mg/kg) i.v. every 2 or every 3 days.

[203, 204]

S3I-1757 (SM)

MDA-MB-468, MDA-MB-231, H358, A549 (less than 200 μM).

B16-F10 melanoma xenograft, daily i.v injections of PBS (control) (n = 3), free S3I-1757 (n = 3), or S3I-1757 encapsulated in PEO114-b-PBCL20 micelles (n = 3) with a dose of 1 mg/kg for 7 days.

[205, 206]

STA-21 (SM)

DU145 (12.2 μM)

NA

[207]

LLL-3 (SM)

Glioblastoma cell U87, U251, U373 (less than 30 μM)

U87 intracranial tumor-brearing athymic nude mice (nu/nu), i.v injection of 50 mg kg − 1 of LLL-3 administered stereotaxically.

[208]

LLL-12 (SM)

HCC cells, SNU387 (0.84 ± 0.23 μM), SNU398 (0.96 ± 0.18 μM), SNU449 (4.38 ± 1.25 μM), and Hep3B (2.39 ± 0.68 μM).

SNU398 tumor-bearing athymic nude mice, 5 mg/kg, i.p injection QD for one month.

[209]

LY5 (SM)

1.637 to 3.347 μmol/L in liver cancer cells, 1.235 to 1.690 μmol/L in colon cancer cells

Colon cancer cell HCT116, QD i.p dosages of 5 mg/kg of LY5 or vehicle control for 11 days.

[210]

SPI (Peptide)

MDA-MB-231, MDA-MB-435), Colo-357, DU145, A549, less than 80 μM.

NA

[211]

PY*LKTK (Peptide)

NIH 3 T3/vSrc colony (more than 500 μM)

NA

[212]

ISS610 (PM)

NIH 3 T3/vSrc colony (more than 1000 μM)

NA

[212]

CJ-1383 (PM)

MDA-MB-231 (11.2 μM), MDA-MB-468 (3.6 μM).

NA

[213]

PM-73G (PM)

MDA-MB-468, A549, more than 30 μM.

Orthotopic MDA-MB-468 breast tumor xenografts, intratumorally (i.t) with 100 μl of PM-73G, formulated in 20% hydroxypropyl-β-cyclodextrin (Trappsol) in PBS to facilitate solubility, 20 days.

[214, 215]

T40214

(STAT3-G-Quartet)

PC3, 5 μM.

MDA-MD-468 or PC-3 tumor bearing athymic nude mice Balb/nu/nu, T40214 (5.0 mg/kg) plus polyethyleneimine (2.5 mg/kg), tail-vein injection, BID.

[216]

T40231

(STAT3-G-Quartet)

PC3, 49 μM

MDA-MD-468 or PC-3 tumor bearing athymic nude mice Balb/nu/nu, T40231 (5.0 mg/kg) plus polyethyleneimine (2.5 mg/kg), tail-vein injection, BID.

[216]

Other modes

STAT3-IN-1 (SM)

IC50 of 1.82 μM and 2.14 μM in HT29 and MDA-MB 231 cells, respectively

Orally, 4 T1 mouse xenograft 10 mg/kg, 20 mg/kg.

[217]

Cyclic STAT3 decoy (DecoyOligodeoxynucleotide)

IC50 of NSCLC is approximately 0.3 μM, the normal lung fibroblasts cell is 300 μM.

NSCLC xenograft, i.v injection, QD, 5 mg/kg/d.

[218]

CTLA4apt-STAT3

(Aptamer)

NA

Karpas299 T cell lymphoma engrafted into athymic nude mice, 782.5 pmol/dose/mouse, i.v BID

[219]

IL-6/IL-6R

Gp130-Fc (Ab)

NA

Colo357 (orthotopic pancreatic tumors cell) in SCID/bg mice, 0.5 mg/kg, 2.5 mg/kg, i.p. twice a week.

[220, 221]

SRC

Indirubin derivatives E804 (SM)

NA

NA

[222]

EGFR

JND3229 (SM)

BaF3, 0.51 ± 0.08 μM (L858R/T790M/C797S), NCI-H1975, 0.31 ± 0.01 μM (L858R/T790M), A431, 0.27 ± 0.18 μM (WT).

NA

[223]

PD153035 (SM)

Human oral squamous cell carcinoma cells KB, KB/V, Hep2, A83, Tca83 and Tca8113, 2.57 ± 0.65, 0.73 ± 0.13, 7.71 ± 0.39, 9.35 ± 0.33, 7.14 ± 0.47 and 10.02 ± 0.28 μmol/l, respectively.

KB, KB/V bearing BALB/c nude mice, 4 or 8 mg/kg, QD i.p injection.

[224]

FGFR

BGJ398 (SM)

SKOV3ip1, less than 4 μM.

NA

[225]

JAK1/2

INCB16562 (SM)

TF-1 (102 ± 36 nM), Bcr-Abl-transduced TF-1 cells (more than 4000 nM).

NA-6.Tu1 xenografts, orally, 25 mg/kg, BID, 42 days.

[226]

CIMO (SM)

HepG2, 7.3 μM.

Huh 7-Luc cells orthotopically athymic nu/nu female mice, 2 mg/kg, 10 mg/kg, 5 days a week i.p.

[227]

JAK2

TG101209

(SM)

Raji (8.18 μmol/L), Ramos (7.23 μmol/L), primary BL cells (4.57 μmol/L)

Ramos-derived tumor xenografts, orally gavage, 100 mg/kg, 7 consecutive days (n = 6 per group).

[228]

TG101348

(SM)

HEL (305 nM), Ba/F3JAK2V617F (270 nM)

NA

[229]

ZT55 (SM)

MCF-7, BT549, K562, KCL-22, U266, HEL, TF-1, cells (18.05—88.31 μM)

Jurkat, Raji, NB4, and Molt-4 (more than 100 μM).

HEL xenograft tumors, athymic BALB/c nude mice, 100 mg/kg body weight, orally QD for 12 successive days.

[230]

Compound 9#

(SM)

B16F10 and 4 T1, little effect.

Tumor-bearing mice, i.t injection, 20 mg/kg, 40 mg/kg.

[231]

BMS-911543

(SM)

SET2, A549, MDA-MB-231, MiaPaCa-2, 0.06—4.7 μM

BALB/c mice were immunized with KLH antigen followed by oral administration of BMS-911543 for 14 days at 3, 10 or 30 mg/kg QD.

[232]

TYK2

Cirsiliol (SM)

NA

ESCC patient-derived xenograft, SCID ice, gavage QD, 10 mg/kg and 50 mg/kg.

[233]

NDI-031301 (SM)

DU.528, KOPT-K1, HPB-ALL, SKW-3, less than 10 μmol/l

KOPT-K1 cells engrafted into NSG mice, 100 mg/kg BID for 29 days.

[234]

SHP1

SC-59 (SM)

NA

6 Huh-7 cells bearing male NCr athymic nude mice, 10 mg/kg/day, orally, QD.

[235]

SC-78 (SM)

HCT-116 (4.2 ± 0.4), HT-29 (4.1 ± 0.3)

NA

[236]

SC-49 (SM)

NA

PLC5 (HCC) bearing NCr athymic nude mice, 5 mg/kg orally QD.

[237]

PP2A

Calyculin A (SM)

NA

NA

[238]