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. Author manuscript; available in PMC: 2017 Nov 1.
Published in final edited form as: Exp Hematol. 2016 Aug 26;44(11):1002–1012. doi: 10.1016/j.exphem.2016.08.006

Table 1.

Heparanase Inhibitors Currently in Development

Drug Name Drug
Category		 Mechanism of
Action		 Clinical Trial Note Refer-
ences
PI-88
(Mupafostat)		 Heparan
Sulfate
Mimetic		 Inhibits
heparanase;
↓FGF-1, FGF-
2, and VEGF		 Phase III in
HCC
(NCT01402908)		 Also releases
TFPI;
↓angiogenesis.		 118–121
PG545 Heparan
Sulfate
Mimetic		 Inhibits
heparanase;
↓FGF-1, FGF-
2, and VEGF.		 Phase I in
advanced solid
tumors.
(NCT02042781)		 In lymphoma
exerts major anti-
tumor effects by ↑
NK cell activity.		 129,134
SST0001
(Roneparstat)		 Heparan
Sulfate
Mimetic		 Inhibits
heparanase;
↓HGF, VEGF,
and MMP-9.
↓shedding of
syndecan-1		 Phase I in R/R
multiple
myeloma.
(NCT01764880)		 Decreased
regrowth of
myeloma tumors
in vivo after
completion of
chemotherapy.		 136,138
M402
(Necuparanib)		 Heparan
Sulfate
Mimetic		 Inhibits
heparanase; ↓
EC sprouting,
FGF2, HB-
EGF, and
VEGF		 Phase I/II trial
for the treatment
of metastatic
pancreatic
cancer.
(NCT01621243)		 143
Suramin Small
Molecule
Inhibitor		 Inhibits
heparanase;
↓FGF-2 and
Caspase-3.		 None ↑HSPG’s,
↓fibrosis and
hepatic tissue
breakdown in
HCC murine
model.		 148,155
OGT2115 Small
Molecule
Inhibitor		 Inhibits
heparanase		 None Suppresses
metastasis induced
by endoplasmic
reticulum stress
from
chemotherapy in
breast cancer cells.		 156
9E8 & H1023 Anti-
heparin
Antibodies		 Inhibition of
heparanase;
↓cellular
invasion and
metastasis.		 None Potent synergism
when combination
of both antibodies
used in myeloma
and lymphoma
murine models.		 149
B-Cell MAP Vaccine Inhibits
heparanase;
↓expression of
VEGF and
bFGF.		 None ↓Microvessel
density and tumor
volume in HCC
murine model.		 152
T-Cell MAP Vaccine CTL
dependent
lysis of tumor
cells, ↑IFN-γ.		 None No activity against
autologous
lymphocytes and
dendritic cells.		 146
Defibrotide Nucleic-
acid based
inhibitors		 ↓heparanase
expression and
tumor growth		 Phase I/II trial
in R/R myeloma
with
combination
chemotherapy.
(NCT00406978)		 No direct
cytotoxic effect on
myeloma.		 144,145
Single Strand
DNA aptamers		 Nucleic-
acid based
inhibitors		 Decreased
expression of
heparanase;
↓tissue
invasion of
tumor cells		 None No direct
cytotoxic effects
on oral cancer
cells. Stable, with
↓complex
formation.		 157
RNAi
(siRNA/shRNA)		 Nucleic-
acid based
inhibitors		 Decreased
expression of
heparanase; ↓
invasion and
migration of
tumor cells		 None Found to work in
multiple cells lines
including: HCC
and melanoma.		 158–160