Abstract
TT-232 is a structural derivative of the peptide hormone somatostatin with selective anti-proliferative and anti-inflammatory properties. It has a strong anti-tumour activity both in vitro and in vivo on a wide range of tumour models and induces apoptosis. Its anti-tumour activity is mediated through the SSTR1 receptor and by the tumour specific isoform of pyruvate kinase. TT-232 has been shown to be a potent neurogenic inflammation inhibitory, anti-inflammatory and analgesic agent with a broader spectrum than presently available anti-inflammatory/analgesic drugs. In animal models it is effective against neurogenic inflammation and blocks neuropathic hyperalgesia where COX-1 or COX-2 inhibitors (e.g. diclofenac or meloxicam) proved ineffective. TT-232 has passed phase I clinical trials without toxicity and significant side effects. Human phase II efficacy studies are ongoing in melanoma indication. Two more oncological indications and phase II clinical trials in inflammatory diseases, including rheumatoid arthritis and burn injuries are in preparation. This compound has the perspective to become the first drug in molecularly targeted therapy of inflammation where a combined effect of anti-inflammatory, analgesic and neurogenic inflammation inhibiting activity can be achieved.
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Abbreviations
- ADME:
-
absorption, distribution, metabolism, excretion
- ALD:
-
approximate lethal dose
- AUD:
-
area under the data
- AUDe :
-
area under the data extrapolated to infinity
- BC:
-
breast cancer
- CLL:
-
chronic lymphoid leukaemia
- Cltot :
-
total clearance
- CNS:
-
central nervous system
- COX:
-
cyclooxigenase
- DTIC:
-
dacarbazine
- GABA:
-
gamma-aminobutyric acid
- GLP:
-
good laboratory practice
- Gly:
-
glycine
- i.m.:
-
intramuscular
- i.v.:
-
intravenous
- LAA:
-
lipo-amino acid
- LD50 :
-
lethal dose 50%
- LS:
-
liposaccharide
- MM:
-
malignant melanoma
- MRT:
-
mean residence time
- NOAEL:
-
no observed adverse effect level
- s.c.:
-
subcutaneous
- SAA:
-
sugar amino acid
- SSTR1:
-
somatostatin receptor type-1
- SSTR2:
-
somatostatin receptor type-2
- SSTR4:
-
somatostatin receptor type-4
- SSTR5:
-
somatostatin receptor type-5
- t1/2 :
-
terminal elimination half-life
- ThR:
-
threonine
- Trp:
-
tryptophan
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Kéri, G., Schwab, R., Szokolóczi, O. et al. TT-232: An Anti-tumour and Anti-inflammatory Peptide Therapeutic in Clinical Development. Int J Pept Res Ther 11, 3–15 (2005). https://doi.org/10.1007/s10989-004-1715-1
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DOI: https://doi.org/10.1007/s10989-004-1715-1