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Tanomastat

Names
IUPAC name (S)-4-(4'-Chlorobiphenyl-4-yl)-4-oxo-2-butanoic acid
Other names BAY 12-9566
Identifiers
CAS Number	179545-77-8
3D model (JSmol)	Interactive image
Beilstein Reference	10706708
ChEMBL	ChEMBL261932
ChemSpider	5293540
PubChem CID	6918336
UNII	AM1ZX94EXH
InChI InChI=1S/C23H19ClO3S/c24-20-12-10-17(11-13-20)16-6-8-18(9-7-16)22(25)14-19(23(26)27)15-28-21-4-2-1-3-5-21/h1-13,19H,14-15H2,(H,26,27)/t19-/m1/s1Key: JXAGDPXECXQWBC-LJQANCHMSA-N
SMILES C1=CC=C(C=C1)SC(CC(=O)C2=CC=C(C=C2)C3=CC=C(C=C3)Cl)C(=O)O
Properties
Chemical formula	C23H19ClO3S
Molar mass	410.91 g·mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Y verify (what is  ?) Infobox references

Tanomastat (development code BAY 12-9566) is a non-peptidic biphenyl inhibitor of matrix metalloproteinases (MMPs), primarily studied for its potential to treat various types of cancer, including osteosarcoma and other malignancies.

Background

Excision of malignant tumors comprises first line treatment for cancer of solid tissues. This procedure not infrequently misses small fragments of the tumor that may have broken off before surgery from the principal site of the disease. These fragments, metastases, often proliferate at quite remote locations where they cause much of the pathology of cancer. A series of proteolytic enzymes present in tumor cells, known as matrix metalloproteinases, help establish growth of these metastases at the newly invaded sites; these proteases are also involved in the formation of new blood vessels that will nourish the invasive cell masses. Consequently, considerable research has been devoted to matrix metalloproteinases as a target for anticancer drugs. Clinical results with these compounds have to date produced equivocal results.

Mechanism of action

Tanomastat works by inhibiting matrix metalloproteinases, which are enzymes involved in the breakdown of the extracellular matrix. This process is often implicated in cancer metastasis, as it allows tumor cells to invade surrounding tissues. By inhibiting MMP activity, tanomastat aims to slow tumor progression and prevent metastasis.

Clinical trials

Tanomastat was evaluated in clinical trials as part of combination therapies with doxorubicin and other chemotherapeutic agents. In a randomized study with osteosarcoma in dogs, the compound did not significantly improve survival compared to placebo. A Phase III trial involving patients with advanced non-small-cell lung cancer (NSCLC) found limited efficacy when used in combination with chemotherapy.

Applications and limitations

While tanomastat demonstrated promising preclinical results, it was ultimately discontinued in human trials due to lack of efficacy. Its primary limitation is related to its inability to significantly prolong survival or reduce tumor size in treated patients, as observed in clinical studies.

See also

• Batimastat
• Marimastat

References

1. Coussens, L. M. (2002). "Matrix Metalloproteinase Inhibitors and Cancer--Trials and Tribulations". Science. 295 (5564): 2387–92. Bibcode:2002Sci...295.2387C. doi:10.1126/science.1067100. PMID 11923519. S2CID 19944201.
2. ^ Moore, A. S. (2007). "Doxorubicin and BAY 12-9566 for the treatment of osteosarcoma in dogs: a randomized, double-blind, placebo-controlled study". J Vet Intern Med. 21 (4): 783–790. doi:10.1892/0891-6640(2007)21[783]2.0.co;2.
3. Christensen, J. G. (2001). "The role of BAY 12-9566 in cancer treatment: a Phase III clinical study". Clin Cancer Res. 7 (5): 1173–1179. doi:10.1200/JCO.2001.19.6.1659.
4. Giaccone, G. (2002). "A Phase III clinical study of BAY 12-9566 in patients with advanced non-small-cell lung cancer". J Clin Oncol. 19 (6): 1659–1668. doi:10.1200/JCO.2001.19.6.1659.

• 4-Chlorophenyl compounds
• Ketones
• Matrix metalloproteinase inhibitors
• Thioethers