Biology Reference
In-Depth Information
inhibitors without affecting other MMPs. Some of these drug leads
include the sultam hydroxamate
27
, β,β-cyclic β-aminohydroxyxamic
acid
28
, macrocycle
29
, and clinical candidate BMS-562392 (
30
)
(Cherney
et al.
, 2006) (see Fig. 6.8). The hydroxamate derivate
31
of the
natural product gelastatin (
32
), as a mixture of
E
/
Z
isomers, showed
potent TACE, as well as MMP inhibition (Park
et al.
, 2006).
N
O
N
N
O
HO
28
O
S
N
O
O
O
NH
O
O
HO
O
27
O
HO
N
H
NH
2
N
O
N
O
CH
3
O
BMS-561392 (
30
)
O
O
N
N
HO
H
N
O
O
O
O
X
29
X = OH; gelastatin (
32
)
X = NHOH; gelastatin
hydroxamates (
31
)
F
3
C
O
O
O
O
2
S
N
HO
OH
H
N
O
O
Ro 32-7315 (
33
)
O
O
2
S
HO
N
TMI-005 (
34
)
O
H
O
N
S
N
O
O
NH
O
H
O
O
N
Pralnacasan (
35
)
Fig. 6.8 Some LPS antagonists that act through TACE or ICE inhibition.
