| Title |
Design and characteristics of cytotoxic fibroblast growth factor 1 conjugate for fibroblast growth factor receptor-targeted cancer therapy
|
|---|---|
| Published in |
Drug Design, Development and Therapy, August 2016
|
| DOI | 10.2147/dddt.s105896 |
| Pubmed ID | |
| Authors |
Anna Szlachcic, Malgorzata Zakrzewska, Michal Lobocki, Piotr Jakimowicz, Jacek Otlewski |
| Abstract |
Fibroblast growth factor receptors (FGFRs) are attractive candidate cancer therapy targets as they are overexpressed in multiple types of tumors, such as breast, prostate, bladder, and lung cancer. In this study, a natural ligand of FGFR, an engineered variant of fibroblast growth factor 1 (FGF1V), was conjugated to a potent cytotoxic drug, monomethyl auristatin E (MMAE), and used as a targeting agent for cancer cells overexpressing FGFRs, similar to antibodies in antibody-drug conjugates. The FGF1V-valine-citrulline-MMAE conjugate showed a favorable stability profile, bound FGFRs on the cell surface specifically, and efficiently released the drug (MMAE) upon cleavage by the lysosomal protease cathepsin B. Importantly, the conjugate showed a prominent cytotoxic effect toward cell lines expressing FGFR. FGF1V-vcMMAE was highly cytotoxic at concentrations even an order of magnitude lower than those found for free MMAE. This effect was FGFR-specific as cells lacking FGFR did not show any increased mortality. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 50% |
| Practitioners (doctors, other healthcare professionals) | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 42 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 10 | 24% |
| Researcher | 6 | 14% |
| Student > Master | 5 | 12% |
| Student > Bachelor | 3 | 7% |
| Other | 3 | 7% |
| Other | 5 | 12% |
| Unknown | 10 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 16 | 38% |
| Agricultural and Biological Sciences | 4 | 10% |
| Chemistry | 4 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
| Immunology and Microbiology | 1 | 2% |
| Other | 3 | 7% |
| Unknown | 12 | 29% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 August 2016.
All research outputs
#20,656,820
of 25,374,647 outputs
Outputs from Drug Design, Development and Therapy
#1,437
of 2,268 outputs
Outputs of similar age
#299,486
of 381,036 outputs
Outputs of similar age from Drug Design, Development and Therapy
#41
of 76 outputs
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