| Stereochemistry | ABSOLUTE |
| Molecular Formula | C45H58N10O9S2 |
| Molecular Weight | 947.134 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 8 / 8 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@@H](O)[C@H](NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](N)CC2=CC=CC=C2)C(=O)N[C@@H](CC3=CC=C(O)C=C3)C(=O)N[C@H](CC4=CNC5=C4C=CC=C5)C(=O)N[C@@H](CCCCN)C(=O)N1)C(N)=O
InChI
InChIKey=SNAJPQVDGYDQSW-DYCFWDQMSA-N
InChI=1S/C45H58N10O9S2/c1-25(56)38(39(48)58)55-45(64)37-24-66-65-23-36(53-40(59)31(47)19-26-9-3-2-4-10-26)44(63)51-34(20-27-14-16-29(57)17-15-27)42(61)52-35(21-28-22-49-32-12-6-5-11-30(28)32)43(62)50-33(41(60)54-37)13-7-8-18-46/h2-6,9-12,14-17,22,25,31,33-38,49,56-57H,7-8,13,18-21,23-24,46-47H2,1H3,(H2,48,58)(H,50,62)(H,51,63)(H,52,61)(H,53,59)(H,54,60)(H,55,64)/t25-,31-,33+,34+,35-,36+,37+,38+/m1/s1
TT-232 is a structural derivative of the natural signal inhibitory peptide somatostatin, with selective antiproliferative and anti-inflammatory properties. TT-232 has no growth hormone release inhibitory effect and does not inhibit the secretion of gastric acid. This analog induces apoptosis in and exerts pronounced antiproliferative effects on various human tumors (colon, pancreas, lymphoma, leukemia, melanoma, hepatoma) cell lines. The growth of human xenografts (prostate, breast carcinoma, lymphoma, melanoma) and animal tumors (colon-26, P-388, S-180, B16, MXT) was inhibited by TT-232 (dose range: 30-750 microg/kg/day) in 54-98% of cases. TT-232 activates SSTR receptors (primarily the SSTR-1), which leads to irreversible cell cycle arrest, followed by secondary induction of apoptosis. TT-232 activates cell cycle inhibitors via SSTR receptors, inhibits tyrosine kinases through interfering with the proliferative signaling cascades, and interacts with an intracellular receptor and an enzyme involved in glycolysis causing translocation of this enzyme to the nucleus, thus inducing apoptosis. TT-232 was a promising candidate in the therapy of human malignancies. TT-232 has passed phase I clinical trials without toxicity and significant side-effects. However TT-232 development has been discontinued.
Originator
Approval Year
PubMed
Sample Use Guides
D10 and 205 cells were implanted into CB17-scid mice which received 30-150-750 ug/kg/day of TT-232 or saline. Animals with 205 cells received twice-daily subcutaneous injections whereas animals with D10 cells were treated with osmotic mini-pumps. TT-232 strongly inhibited proliferation of all cell lines in vitro and tumour growth in vivo. Two out of 8 animals (30-150 ug/kg) in the 205 model and one out of 8 (150 ug/kg) in the D10 model became completely tumour-free at the 11th and 9th day of treatment, respectively.
Route of Administration:
Other
SUBSTANCE RECORD
