Endostatin
| Endostatin | ||
|---|---|---|
|
||
| Endostatin dimer, surface model on the left, ribbon model on the right, with zinc as a ball, according to PDB 1BNL | ||
| Properties of human protein | ||
| Mass / length primary structure | 183 amino acids | |
| Secondary to quaternary structure | Dimer | |
| Precursor | Collagen α1-XVIII (1731 aas) | |
| Identifier | ||
| Gene name | COL18A1 | |
| External IDs | ||
| Occurrence | ||
| Parent taxon | multicellular animals | |
As endostatin a cleavage product (molecular mass 20 kDa ) of collagen referred XVIII, the first time in 1997 by O'Reilly et al. as a product of hemangioendothelioma cells was isolated. Mutations in the gene coding for endostatin part of COL18A1 - gene are at increased risk of prostate cancer associated.
effect
Endostatin is a direct endogenous angiogenesis - inhibitor , the in vitro the proliferation and migration of endothelial cells and in vivo the growth of Lewis Lung - xenograft could stop tumors in mice.
There is great therapeutic hope in the protein . The exact mechanisms of action (for example the corresponding receptors) are currently being intensively researched.
In clinical phase I studies, no undesirable effects were observed, nor did resistance develop. However, the success of the treatment also remained below expectations. Various new approaches to experimental therapy, such as: B. Gene Therapy.
Perspectives
Current publications (Kalluri, Molecular Cell, 2004) shine a light inside the network of the endostatin effect. It is becoming apparent that the success of the therapy depends crucially on the correct dosage and - as with many other cancer therapies - on the tumor entity.
Endostatin was developed and patented in Judah Folkman 's laboratory at Boston Children's Hospital . Boston Children's Hospital licensed EntreMed, Inc. in the mid-1990s . The company developed endostatin into clinical phase III. After a change of strategy, EntreMed gave up further development in 2004 and returned the license rights to Boston Children's Hospital. Boston Children's Hospital is currently seeking a new licensee for endostatin. Currently (as of December 2016) several phase III and IV studies are running with Endostar , the recombinantly produced variant of endostatin.
literature
- Elena V. Rosca, Jacob E. Koskimaki, Corban G. Rivera, Niranjan B. Pandey, Amir P. Tamiz, Aleksander S. Popel : Anti-angiogenic peptides for cancer therapeutics. In: Current Pharmaceutical Biotechnology . Volume 12, Number 8, August 2011, ISSN 1873-4316 , pp. 1101-1116, PMID 21470139 , PMC 3114256 (free full text) (review).
Individual evidence
- ↑ InterPro entry
- ↑ UniProt P39060
- ↑ Robert Benezra, Shahin Rafii: Endostatin's endpoints - Deciphering the endostatin antiangiogenic pathway . In: Cancer Cell . 5, No. 3, March 2004, pp. 205-206. ISSN 1535-6108 . doi : 10.1016 / S1535-6108 (04) 00057-1 . PMID 15050911 .
- ^ Judah Folkman : Role of angiogenesis in tumor growth and metastasis . In: Seminars in Oncology . 29, No. 6 Suppl 16, December 2002, pp. 15-18. ISSN 0093-7754 . doi : 10.1053 / sonc.2002.37263 . PMID 12516034 .
- ↑ a b Endostatin: A potent angiogenesis inhibitor. (No longer available online.) In: childrensinnovations.org. Archived from the original on December 21, 2016 ; Retrieved December 20, 2016 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.
- ↑ K. Grosios: Endostatin (EntreMed). In: IDrugs: the investigational drugs journal. Volume 3, Number 7, July 2000, pp. 799-810, PMID 16080055 .
- ↑ Endostatin in Phase III and IV. Clinicaltrials.gov, accessed December 20, 2016
