Tanomastat

Last updated
Tanomastat
Tanomastat.svg
Names
IUPAC name
(S)-4-(4'-Chlorobiphenyl-4-yl)-4-oxo-2-[(phenylsulfanyl)methyl]butanoic acid
Other names
BAY 12-9566
Identifiers
3D model (JSmol)
10706708
ChEMBL
ChemSpider
PubChem CID
UNII
  • 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/s1
    Key: JXAGDPXECXQWBC-LJQANCHMSA-N
  • C1=CC=C(C=C1)SC[C@@H](CC(=O)C2=CC=C(C=C2)C3=CC=C(C=C3)Cl)C(=O)O
Properties
C23H19ClO3S
Molar mass 410.91 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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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.

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. [1]

See also

Related Research Articles

<span class="mw-page-title-main">Metastasis</span> Spread of a disease inside a body

Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, are metastases (mets). It is generally distinguished from cancer invasion, which is the direct extension and penetration by cancer cells into neighboring tissues.

Matrix metalloproteinases (MMPs), also known as matrix metallopeptidases or matrixins, are metalloproteinases that are calcium-dependent zinc-containing endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily.

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<span class="mw-page-title-main">Thrombospondin 1</span> Protein-coding gene in the species Homo sapiens

Thrombospondin 1, abbreviated as THBS1, is a protein that in humans is encoded by the THBS1 gene.

<span class="mw-page-title-main">MMP2</span> Protein-coding gene in humans

72 kDa type IV collagenase also known as matrix metalloproteinase-2 (MMP-2) and gelatinase A is an enzyme that in humans is encoded by the MMP2 gene. The MMP2 gene is located on chromosome 16 at position 12.2.

<span class="mw-page-title-main">MMP7</span> Protein-coding gene in humans

Matrilysin also known as matrix metalloproteinase-7 (MMP-7), pump-1 protease (PUMP-1), or uterine metalloproteinase is an enzyme in humans that is encoded by the MMP7 gene. The enzyme has also been known as matrin, putative metalloproteinase-1, matrix metalloproteinase pump 1, PUMP-1 proteinase, PUMP, metalloproteinase pump-1, putative metalloproteinase, MMP). Human MMP-7 has a molecular weight around 30 kDa.

<span class="mw-page-title-main">MMP10</span> Protein-coding gene in the species Homo sapiens

Stromelysin-2 also known as matrix metalloproteinase-10 (MMP-10) or transin-2 is an enzyme that in humans is encoded by the MMP10 gene.

<span class="mw-page-title-main">MMP26</span> Protein-coding gene in the species Homo sapiens

Matrix metalloproteinase-26 also known as matrilysin-2 and endometase is an enzyme that in humans is encoded by the MMP26 gene.

<span class="mw-page-title-main">MMP11</span> Protein-coding gene in humans

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<span class="mw-page-title-main">RECK</span> Protein-coding gene in the species Homo sapiens

Reversion-inducing-cysteine-rich protein with kazal motifs, also known as RECK, is a human gene, thought to be a metastasis suppressor.

<span class="mw-page-title-main">MMP25</span> Protein-coding gene in the species Homo sapiens

Matrix metalloproteinase-25 is an enzyme that in humans is encoded by the MMP25 gene.

<span class="mw-page-title-main">MMP28</span> Protein-coding gene in the species Homo sapiens

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A matrix metalloproteinase inhibitor inhibits matrix metalloproteinases. Because they inhibit cell migration, they have antiangiogenic effects. They are endogenous or exogenous.

<span class="mw-page-title-main">MMP8</span> Protein-coding gene in the species Homo sapiens

Neutrophil collagenase, also known as matrix metalloproteinase-8 (MMP-8) or PMNL collagenase (MNL-CL), is a collagen cleaving enzyme which is present in the connective tissue of most mammals. In humans, the MMP-8 protein is encoded by the MMP8 gene. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the enzyme encoded by this gene is stored in secondary granules within neutrophils and is activated by autolytic cleavage.

Metalloprotease inhibitors are cellular inhibitors of the Matrix metalloproteinases (MMPs). MMPs belong to a family of zinc-dependent neutral endopeptidases. These enzymes have the ability to break down connective tissue. The expression of MMPs is increased in various pathological conditions like inflammatory conditions, metabolic bone disease, to cancer invasion, metastasis and angiogenesis. Examples of diseases are periodontitis, hepatitis, glomerulonephritis, atherosclerosis, emphysema, asthma, autoimmune disorders of skin and dermal photoaging, rheumatoid arthritis, osteoarthritis, multiple sclerosis, Alzheimer's disease, chronic ulcerations, uterine involution, corneal epithelial defects, bone resorption and tumor progression and metastasis. Due to the role of MMPs in pathological conditions, inhibitors of MMPs may have therapeutic potential. Several other proteins have similar inhibitory effects, however none as effective. They might have other biological activities which have yet been fully characterised.

<span class="mw-page-title-main">Desmoplasia</span> Growth of fibrous or connective tissue

In medicine, desmoplasia is the growth of fibrous connective tissue. It is also called a desmoplastic reaction to emphasize that it is secondary to an insult. Desmoplasia may occur around a neoplasm, causing dense fibrosis around the tumor, or scar tissue (adhesions) within the abdomen after abdominal surgery.

Angiogenesis is the process of forming new blood vessels from existing blood vessels, formed in vasculogenesis. It is a highly complex process involving extensive interplay between cells, soluble factors, and the extracellular matrix (ECM). Angiogenesis is critical during normal physiological development, but it also occurs in adults during inflammation, wound healing, ischemia, and in pathological conditions such as rheumatoid arthritis, hemangioma, and tumor growth. Proteolysis has been indicated as one of the first and most sustained activities involved in the formation of new blood vessels. Numerous proteases including matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase domain (ADAM), a disintegrin and metalloproteinase domain with throbospondin motifs (ADAMTS), and cysteine and serine proteases are involved in angiogenesis. This article focuses on the important and diverse roles that these proteases play in the regulation of angiogenesis.

<span class="mw-page-title-main">Metastatic breast cancer</span> Type of cancer

Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumors, secondaries or stage IV breast cancer, is a stage of breast cancer where the breast cancer cells have spread to distant sites beyond the axillary lymph nodes. There is no cure for metastatic breast cancer; there is no stage after IV.

Tumstatin is a protein fragment cleaved from collagen that serves as both an antiangiogenic and proapoptotic agent. It has similar function to canstatin, endostatin, restin, and arresten, which also affect angiogenesis. Angiogenesis is the growth of new blood vessels from pre-existing blood vessels, and is important in tumor growth and metastasis. Angiogenesis is stimulated by many growth factors, the most prevalent of which is vascular endothelial growth factor (VEGF).

<span class="mw-page-title-main">Invasion (cancer)</span> Direct extension and penetration by cancer cells into neighboring tissues

Invasion is the process by which cancer cells directly extend and penetrate into neighboring tissues in cancer. It is generally distinguished from metastasis, which is the spread of cancer cells through the circulatory system or the lymphatic system to more distant locations. Yet, lymphovascular invasion is generally the first step of metastasis.

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.