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MIGUEL FERNÁNDEZ BRAÑA Y COLS. AN. R. ACAD. NAC. FARM.

peutic properties has raised a new interest in this molecule, and recently the FDA
has approved its use in the treatment of ENL (Erythema Nodosum Leprosum), an
acute manifestationof leprae. Besides, thalidomide is nowadays going through cli-
nical assays (PhaseII/III) in multiple myeloma, breast, prostate, kidney and lung
tumours, showing good results. This article offers an overview of thalidomide
properties focusing on its inhibition of angiogenesis, which would be responsible,
at least partially, of its antineoplastic and teratogenic activity.

KeyWorks: Thalidomide.— TNF-a.— Angiogenesis.— Cancer.

EXTENSIVE ABSTRACT

Since the early 1960’s when Thalidomide’s use was banned due to its therato-
genic activity, this drug has been widely studied finding therapeutic properties,
which have aroused a new interest for the molecule. Recently, FDA has approved
its use in the treatment of ENL (Erythema Nodosum Leprosum), an acute leprosies
secondary effect. Besides, nowadays clinical trials (Phase II/III) are conducted in
breast, prostate, lung, kidney and multiple myeloma cancers showing promising
results. This paper offers a review of some therapeutic properties of Thalidomide,
describing its evolution since the moment of this marketing and withdrawal.

During a program directed to the preparation of semi synthetic antibiotics,
german firm Grünenthal obtained a side product with higher sedative properties
than barbiturics used to date. In the middle 1950’s this drug named Thalidomide
was marketed to treat some disorders during pregnancy. A few years later of its
use. Recently, the chance discovery of new therapeutic effects such as great acti-
vity against nodular Erythema causes by antileprosy chemotherapy has led the
U. S. Food and Drug Administration (FDA) to the bidirectional regulatory action on
the expression of TFN-a, wich has opened the possibility of prescribing this drug
in cases of rheumatoid arthritis, AIDS cachexia and transplant rejection.

Growing interest has aroused towards Thalidomide after the discovery of its
antiangiogenic activity because it could be applied in the treatment of malignant
tumours. In fact, nowadays clinical trial (Phase II/III) are conducted in breast,
prostate, lung, kidney and multiple myeloma cancers showing promising results.

Despite the efforts directed to find an explanation for its mechanism of action
(there are more that 30 theories published) theratogenic and therapeutic proper-
ties are not fully understood. A possible approach could be to admit the interca-
lation with DNA thought multiple box GGGcGG. Thalidomide or a derivate would
bind specifically to a promoting site GC, of these genes and affecting therefore the
synthesis of the corresponding angiogenic proteins severe birth defects, along with
stopping blood vessels growth and tumours supply of nutrients. Nevertheless,
Thalidomide hasn’t shown mutagenic activity in laboratory tests. It has been po-
inted out the possibility of a metabolic activation even if no active metabolite has
been detected to date.

Also interesting is the fact that Thalidomide has always been used in the race-
mic form. When separated tests were performed which each enanthiomer, a phy-

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