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Growth factor receptor tumor target tumor (tumor) refers to a new organism formed by the proliferation of local tissue cells under the action of various tumor-causing factors.
Growth factors are closely related to tumor formation and expansion.
Growth factor receptors on the surface of tumors have always been popular targets for tumor-targeted drugs.
The most representative is the epidermal cell growth factor receptor (EGFR) family.
The epidermal growth factor receptor (EGFR) targeted and marketed antibody drugs include Cetuximab, Panitumumab, and Necitumumab.
Other members of this family, HER2 (human EGFR related-2) (Trastuzumab, Pertuzumab, Trastuzumab, Deruxtecan), and HER3 (Patritumab, Deruxtecan) all have antibody drugs on the market or have potential blockbuster drugs under development.
Vascular endothelial cell growth factor receptor (VEGFR) also has related targeted antibody drugs or fusion proteins on the market.
Which family will the next innovative growth factor receptor target be? Will it create the brilliance of the EGFR target? FGFR targeted drugs Fibroblast growth factor receptor family (FGFR) belongs to the receptor kinase family, which includes four receptor subtypes (FGFR-1, 2, 3 and 4) encoded by four closely related genes And some heterogeneous molecules, they form a ternary complex with 18 different fibroblast growth factors (FGF), and then trigger a series of signal transduction pathways, participate in the regulation of physiological processes in the organism, such as: embryonic development, wounds Healing and angiogenesis, etc.
The downstream of FGFR involves multiple signaling pathways with different functions.
Similar to epidermal growth factor (EGFR), the abnormality of FGFR signaling pathway has also become an important cause of many tumors.At present, many small molecule inhibitors targeting Pan-FGFR and specific FGFR subtypes have been in the late clinical stage, covering major solid tumor indications such as breast cancer, non-small cell lung cancer, and gastric cancer, with great potential.
In the field of antibody drug research and development, antibody drugs targeting the four subtypes of the FGFR family have been developed in the preclinical and clinical stages, and most of them target the subtype of FGFR2.
At present, several antibody drugs targeting FGFR2 are in the preclinical stage, including AVEO's GP369, Galaxy Bio's HuGAL-FR21, and Fibron, Attogen, Daiichi Sankyo, U.
Wroclaw and other companies' patented antibodies.
The only antibody drugs in the clinical stage are Bayer's Aprutumab and its ADC, and Five Prime's Bemarituzumab (the antibody sequence is consistent with HuGAL-FR21, and the removal of fucose enhances ADCC development).
Bemarituzumab has been developed to clinical phase 3.
Five Prime announced the results of a phase 2 clinical trial for gastric cancer on November 10, 2020: Compared with chemotherapy, the use of Bemarituzumab combined with chemotherapy can improve the median progression-free survival of patients with advanced gastric cancer ( PFS) increased from 7.
4 months to 9.
5 months.
More importantly, the overall survival (OS) of patients has also been significantly improved.
In this global clinical trial, patients included gastric cancer and gastroesophageal junction (GEJ) cancer.
Bemarituzumab will be approved in the future and will be used in combination with chemotherapy.
It is very likely to be used as a first-line treatment for patients with advanced gastric cancer.
It has great potential! Structural features of FGFR2 protein FGFR protein has a typical tyrosine kinase structure.
The extracellular region is composed of three Ig (Immunoglobulin) domains (IgI, IgII, IgIII Domain), of which IgII Domain and IgIII Domain are formed The binding pocket of FGF ligand has an acidic box connecting the acidic amino acid sequence between IgI Domain and IgII Domain.Among them, 4 different genes encode FGFR protein, and alternatively splicing exon 8 or 9 at FGFR1, FGFR2 and FGFR3 will form two subtypes of IgIII Domain (IIIb, IIIc respectively).
The structure diagram of FGFR2 is as follows: Generally speaking, the more common naming rule for FGFR is FGFR(α/β)-III b/c, where α or β represents the number of domains contained in FGFR, and if it contains IgI, IgII, IgIII Domain, it is α subtype, if it only contains IgII, IgIII Domain is β subtype; -III b/c represents the type of IgIII Domain, half of IgIII has part a encoded by exon 7, such as exon 8.
The other half is called type b.
If it encodes exon 9, the other half is called type c.
In many cases, -III b/c will be abbreviated as b/c.
For example, FGFR2 beta IIIb is also called FGFR2 (beta) b.
The extracellular region Ig Domain of the protein only contains IgII Domain and IgIII Domain, and IgIII Domain is encoded by exon 8.
The functional characteristics of FGFR2 protein The IgI Domain and acidic box of FGFR2 are believed to play a role in inhibiting the binding of FGFR2 and FGF growth factor, so FGFR2 α subtype and FGFR2 β subtype have different physiological characteristics.
Classified by IgIII Domain, FGFR2 can be divided into FGFR2-III b (FGFR2b) and FGFR2-III c (FGFR2c).
FGFR2-III c is mainly expressed in mesenchymal cells and can bind FGF1 and FGF2 with high affinity, while FGFR2-III b It is mainly expressed in epithelial cells and can bind to FGF1 and KGF family cell growth factors (FGF7, FGF10, FGF22) with high affinity, and FGFR2-III b is the only receptor of KGF family cell growth factors, also known as KGFR. KGF family cell growth factors and KGFR (FGFR2-III b) are highly expressed in a variety of solid tumors, and they are mainly caused by FGFR2 gene amplification and hyperactivation of this signaling pathway to cause tumor cell proliferation, survival and EMT, etc.
, which are poor in many tumors.
As a prognostic marker, FGFR2-III b is a very potential solid tumor target.
Specific antibodies against different subtypes of FGFR2 can be obtained by immunizing and screening proteins containing different domains.
For example, in the US8101723B2 patent, by selecting the combination of FGFR2 alpha IIIc and FGFR2 beta IIIc or FGFR2 beta IIIb and FGFR2 beta IIIc to immunize mice, three types of tables were finally obtained for IgI Domain, IgII Domain and IgIII Domain, IgIIIb Domain, etc.
Bit of antibody.
Based on the in-depth understanding of the FGFR2 target, Kaifa Biotechnology has prepared the FGFR2 series of proteins, which include different domains and subtypes, and have been verified for activity, consistent with the literature reports, to help differentiated immunity and antibody development.
FGFR2 different subtypes and domain and antibody ELISA data FGFR2 different subtypes and domain and antibody SPR data For product information, please contact: website: email: support@kactusbio.
com hotline: 400-614-0008 phone: Shanghai Region: 15021367472, 18256917205 Jiangsu, Shandong: 17827834427 Zhejiang Beijing: 15801006807 Other regions: 18256917205 Kactus Biosystems is an innovative protein and antibody international biotechnology company driven by research and development, mainly focusing on immunotherapy and diagnosis market.
Kai Tu Bio focuses on global innovative drug research and development corporate customers, providing CRO services and catalog products based on structural design of functional target proteins, especially membrane proteins.
The main founding team of Kai Tu Biology comes from scientists and business managers with many years of experience in the biomedical industry from world-class companies and research institutions.
The copyright statement welcomes personal forwarding and sharing.
Any other media or website that needs to reprint or quote the copyrighted content of this website must be authorized and marked "Reprinted from: Biopharmaceutical Editor" in a prominent position.
Growth factors are closely related to tumor formation and expansion.
Growth factor receptors on the surface of tumors have always been popular targets for tumor-targeted drugs.
The most representative is the epidermal cell growth factor receptor (EGFR) family.
The epidermal growth factor receptor (EGFR) targeted and marketed antibody drugs include Cetuximab, Panitumumab, and Necitumumab.
Other members of this family, HER2 (human EGFR related-2) (Trastuzumab, Pertuzumab, Trastuzumab, Deruxtecan), and HER3 (Patritumab, Deruxtecan) all have antibody drugs on the market or have potential blockbuster drugs under development.
Vascular endothelial cell growth factor receptor (VEGFR) also has related targeted antibody drugs or fusion proteins on the market.
Which family will the next innovative growth factor receptor target be? Will it create the brilliance of the EGFR target? FGFR targeted drugs Fibroblast growth factor receptor family (FGFR) belongs to the receptor kinase family, which includes four receptor subtypes (FGFR-1, 2, 3 and 4) encoded by four closely related genes And some heterogeneous molecules, they form a ternary complex with 18 different fibroblast growth factors (FGF), and then trigger a series of signal transduction pathways, participate in the regulation of physiological processes in the organism, such as: embryonic development, wounds Healing and angiogenesis, etc.
The downstream of FGFR involves multiple signaling pathways with different functions.
Similar to epidermal growth factor (EGFR), the abnormality of FGFR signaling pathway has also become an important cause of many tumors.At present, many small molecule inhibitors targeting Pan-FGFR and specific FGFR subtypes have been in the late clinical stage, covering major solid tumor indications such as breast cancer, non-small cell lung cancer, and gastric cancer, with great potential.
In the field of antibody drug research and development, antibody drugs targeting the four subtypes of the FGFR family have been developed in the preclinical and clinical stages, and most of them target the subtype of FGFR2.
At present, several antibody drugs targeting FGFR2 are in the preclinical stage, including AVEO's GP369, Galaxy Bio's HuGAL-FR21, and Fibron, Attogen, Daiichi Sankyo, U.
Wroclaw and other companies' patented antibodies.
The only antibody drugs in the clinical stage are Bayer's Aprutumab and its ADC, and Five Prime's Bemarituzumab (the antibody sequence is consistent with HuGAL-FR21, and the removal of fucose enhances ADCC development).
Bemarituzumab has been developed to clinical phase 3.
Five Prime announced the results of a phase 2 clinical trial for gastric cancer on November 10, 2020: Compared with chemotherapy, the use of Bemarituzumab combined with chemotherapy can improve the median progression-free survival of patients with advanced gastric cancer ( PFS) increased from 7.
4 months to 9.
5 months.
More importantly, the overall survival (OS) of patients has also been significantly improved.
In this global clinical trial, patients included gastric cancer and gastroesophageal junction (GEJ) cancer.
Bemarituzumab will be approved in the future and will be used in combination with chemotherapy.
It is very likely to be used as a first-line treatment for patients with advanced gastric cancer.
It has great potential! Structural features of FGFR2 protein FGFR protein has a typical tyrosine kinase structure.
The extracellular region is composed of three Ig (Immunoglobulin) domains (IgI, IgII, IgIII Domain), of which IgII Domain and IgIII Domain are formed The binding pocket of FGF ligand has an acidic box connecting the acidic amino acid sequence between IgI Domain and IgII Domain.Among them, 4 different genes encode FGFR protein, and alternatively splicing exon 8 or 9 at FGFR1, FGFR2 and FGFR3 will form two subtypes of IgIII Domain (IIIb, IIIc respectively).
The structure diagram of FGFR2 is as follows: Generally speaking, the more common naming rule for FGFR is FGFR(α/β)-III b/c, where α or β represents the number of domains contained in FGFR, and if it contains IgI, IgII, IgIII Domain, it is α subtype, if it only contains IgII, IgIII Domain is β subtype; -III b/c represents the type of IgIII Domain, half of IgIII has part a encoded by exon 7, such as exon 8.
The other half is called type b.
If it encodes exon 9, the other half is called type c.
In many cases, -III b/c will be abbreviated as b/c.
For example, FGFR2 beta IIIb is also called FGFR2 (beta) b.
The extracellular region Ig Domain of the protein only contains IgII Domain and IgIII Domain, and IgIII Domain is encoded by exon 8.
The functional characteristics of FGFR2 protein The IgI Domain and acidic box of FGFR2 are believed to play a role in inhibiting the binding of FGFR2 and FGF growth factor, so FGFR2 α subtype and FGFR2 β subtype have different physiological characteristics.
Classified by IgIII Domain, FGFR2 can be divided into FGFR2-III b (FGFR2b) and FGFR2-III c (FGFR2c).
FGFR2-III c is mainly expressed in mesenchymal cells and can bind FGF1 and FGF2 with high affinity, while FGFR2-III b It is mainly expressed in epithelial cells and can bind to FGF1 and KGF family cell growth factors (FGF7, FGF10, FGF22) with high affinity, and FGFR2-III b is the only receptor of KGF family cell growth factors, also known as KGFR. KGF family cell growth factors and KGFR (FGFR2-III b) are highly expressed in a variety of solid tumors, and they are mainly caused by FGFR2 gene amplification and hyperactivation of this signaling pathway to cause tumor cell proliferation, survival and EMT, etc.
, which are poor in many tumors.
As a prognostic marker, FGFR2-III b is a very potential solid tumor target.
Specific antibodies against different subtypes of FGFR2 can be obtained by immunizing and screening proteins containing different domains.
For example, in the US8101723B2 patent, by selecting the combination of FGFR2 alpha IIIc and FGFR2 beta IIIc or FGFR2 beta IIIb and FGFR2 beta IIIc to immunize mice, three types of tables were finally obtained for IgI Domain, IgII Domain and IgIII Domain, IgIIIb Domain, etc.
Bit of antibody.
Based on the in-depth understanding of the FGFR2 target, Kaifa Biotechnology has prepared the FGFR2 series of proteins, which include different domains and subtypes, and have been verified for activity, consistent with the literature reports, to help differentiated immunity and antibody development.
FGFR2 different subtypes and domain and antibody ELISA data FGFR2 different subtypes and domain and antibody SPR data For product information, please contact: website: email: support@kactusbio.
com hotline: 400-614-0008 phone: Shanghai Region: 15021367472, 18256917205 Jiangsu, Shandong: 17827834427 Zhejiang Beijing: 15801006807 Other regions: 18256917205 Kactus Biosystems is an innovative protein and antibody international biotechnology company driven by research and development, mainly focusing on immunotherapy and diagnosis market.
Kai Tu Bio focuses on global innovative drug research and development corporate customers, providing CRO services and catalog products based on structural design of functional target proteins, especially membrane proteins.
The main founding team of Kai Tu Biology comes from scientists and business managers with many years of experience in the biomedical industry from world-class companies and research institutions.
The copyright statement welcomes personal forwarding and sharing.
Any other media or website that needs to reprint or quote the copyrighted content of this website must be authorized and marked "Reprinted from: Biopharmaceutical Editor" in a prominent position.
