Recifercept
(Synonyms: TA-46; sFGFR3; PF-07256472)
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Recifercept (TA-46) is a FGFR3 that binds to FGF1, FGF2, FGF8, FGF9, FGF16, FGF17, FGF18, and FGF20 with Kd values of 0.74, 3.4, 4.28, 0.75, 0.94, 2.73, 4.17, and 7.1 nM, respectively. Recifercept acts as a decoy receptor, preventing FGF from binding to mutant FGFR3. Recifercept impairs MAPK and reduces FGF-induced ERK phosphorylation. Recifercept corrects achondroplastic bone growth and craniofacial abnormalities. Recifercept prevents visceral obesity and restores glucose metabolism, insulin/glucagon, hepatic responses, and energy metabolism. Recifercept can be used for research on idiopathic pulmonary fibrosis.
For research use only. We do not sell to patients.
- Purity : 97.10%
- CAS No.: 2226238-09-9
- Molecular Weight:37.72 kDa
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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Biological Activity
Description
Recifercept (TA-46) is a FGFR3 that binds to FGF1, FGF2, FGF8, FGF9, FGF16, FGF17, FGF18, and FGF20 with Kd values of 0.74, 3.4, 4.28, 0.75, 0.94, 2.73, 4.17, and 7.1 nM, respectively. Recifercept acts as a decoy receptor, preventing FGF from binding to mutant FGFR3. Recifercept impairs MAPK and reduces FGF-induced ERK phosphorylation. Recifercept corrects achondroplastic bone growth and craniofacial abnormalities. Recifercept prevents visceral obesity and restores glucose metabolism, insulin/glucagon, hepatic responses, and energy metabolism. Recifercept can be used for research on idiopathic pulmonary fibrosis[1][2][3][4][5][6][7].
Species Reactivity
Human
IC50 & Target
[1]|
FGFR3 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| BaF3 | IC50 |
4.3 nM
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Inhibition of FGF1-stimulated proliferation of BaF3 cells expressing human FGFR3 IIIc WT assessed by intracellular ATP luminescence using CellTiter Glo after 72 hrs incubation.
Inhibition of FGF1-stimulated proliferation of BaF3 cells expressing human FGFR3 IIIc WT assessed by intracellular ATP luminescence using CellTiter Glo after 72 hrs incubation.
|
33370388 |
| BaF3 | IC50 |
3.6 nM
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Inhibition of FGF1-stimulated proliferation of BaF3 cells expressing human FGFR3 IIIc G380R assessed by intracellular ATP luminescence using CellTiter Glo after 72 hrs incubation.
Inhibition of FGF1-stimulated proliferation of BaF3 cells expressing human FGFR3 IIIc G380R assessed by intracellular ATP luminescence using CellTiter Glo after 72 hrs incubation.
|
33370388 |
In Vitro
Anti-cancerLipid MetabolismOthers
Anti-cancer
Recifercept (72 h) inhibits the proliferation of BaF3 cells expressing FGFR3 IIIc WT or FGFR3 IIIc G380R stimulated by FGF1, with IC50 values of approximately 4.3 nM and 3.6 nM, respectively[4].
Recifercept (2 μM; 30 min) reduces FGF2-induced phosphorylation of PLCγ1, MEK1/2, and ERK in RCS cells[4].
Recifercept (2 μM; 30 min) reduces FGF2-induced phosphorylation of PLCγ1, MEK1/2, and ERK in RCS cells[4].
Lipid Metabolism
Recifercept exposure increases anti-adipogenic and brown tissue activation markers in ex vivo bone marrow-derived MSCs from Fgfr3ach/+ mice and decreases mature adipocyte gene expression[3].
Others
Recifercept (0-250 ng/mL; 2 h) binds hFGF2, mFGF2, hFGF9, and hFGF18 in a dose-dependent manner in a cell-free ELISA[1].
Recifercept (0-20 ng/mL; 10 min) competes with endogenous FGFR3 for binding to FGF2 on ATDC5 chondrocytes[1].
Recifercept (0-20 ng/mL; 10 min) reduces FGF-induced FGFR and ERK phosphorylation without activating STAT1 in Fgfr3ach/+ chondrocytes[1].
Recifercept (20 ng/mL; 72 h) restores ATDC5 chondrocyte proliferation in the presence of FGF2, FGF9, or FGF18[1].
Recifercept (20 ng/mL; 7 days) restores ATDC5 chondrocyte differentiation and increases Col2, Col10, and Sox9 expression relative to FGF alone[1].
Recifercept (20 ng/mL) does not alter Fgfr3 gene expression in Fgfr3ach/+ chondrocytes[1].
Recifercept (5 μg/mL) binds hFGF1, hFGF2, hFGF9, hFGF16, hFGF20, hFGF8, hFGF17, and hFGF18 in surface plasmon resonance with KD values of 0.74, 3.4, 0.75, 0.94, 7.1, 4.28, 2.73, and 4.17 nM, respectively[4].
Recifercept (0-20 ng/mL; 10 min) competes with endogenous FGFR3 for binding to FGF2 on ATDC5 chondrocytes[1].
Recifercept (0-20 ng/mL; 10 min) reduces FGF-induced FGFR and ERK phosphorylation without activating STAT1 in Fgfr3ach/+ chondrocytes[1].
Recifercept (20 ng/mL; 72 h) restores ATDC5 chondrocyte proliferation in the presence of FGF2, FGF9, or FGF18[1].
Recifercept (20 ng/mL; 7 days) restores ATDC5 chondrocyte differentiation and increases Col2, Col10, and Sox9 expression relative to FGF alone[1].
Recifercept (20 ng/mL) does not alter Fgfr3 gene expression in Fgfr3ach/+ chondrocytes[1].
Recifercept (5 μg/mL) binds hFGF1, hFGF2, hFGF9, hFGF16, hFGF20, hFGF8, hFGF17, and hFGF18 in surface plasmon resonance with KD values of 0.74, 3.4, 0.75, 0.94, 7.1, 4.28, 2.73, and 4.17 nM, respectively[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay[1]
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Cell Line:Mouse ATDC5 chondrocytes
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Concentration:Recifercept 0 or 20 ng/mL; FGF2/FGF9/FGF18 100 pg/mL
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Incubation Time:72 h
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Result:Restored proliferation of ATDC5 cells.
Cell Differentiation Assay[1]
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Cell Line:Mouse ATDC5 chondrocytes
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Concentration:Recifercept 0 or 20 ng/mL; FGF2/FGF9/FGF18 100 pg/mL
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Incubation Time:7 days
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Result:Restored differentiation of ATDC5 cells and increased collagen type 2 (Col2), collagen type 10 (Col10), and Sox9 gene expression relative to FGF alone.
Cell Proliferation Assay[4]
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Cell Line:Murine pro-B lymphocyte BaF3 cells overexpressing human FGFR3 IIIc WT or human FGFR3 IIIc G380R; non-transfected BaF3 cells as control
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Concentration:Various concentrations
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Incubation Time:72 h
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Result:Reduced FGF1-stimulated proliferation in BaF3 cells expressing FGFR3 IIIc WT with an IC50 of 4.3 nM.
Reduced FGF1-stimulated proliferation in BaF3 cells expressing FGFR3 IIIc G380R with an IC50 of 3.6 nM.
Western Blot Analysis[4]
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Cell Line:RCS (Rat ChondroSarcoma) cells
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Concentration:2 μM
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Incubation Time:30 min (stimulation); overnight at +4°C (primary antibody incubation)
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Result:FGF2-induced phosphorylation of PLCγ1, MEK1/2, and ERK was reduced by 2 μM Recifercept.
Phosphorylated phospholipase C and MAP-kinase pathway via pMEK1/2 and pERK were downregulated.
In Vivo
Carbohydrate MetabolismLipid MetabolismOthers
Carbohydrate Metabolism
Lipid Metabolism
sFGFR3 (2.5 mg/kg; s.c.; twice weekly; from day 3 to day 21; early postnatal) prevents atypical visceral obesity and several metabolic deregulations in Fgfr3ach/+ mice, restoring fat distribution and glucose metabolism toward WT-like profiles[3].
Others
Recifercept (0.25-2.5 mg/kg; s.c.; twice weekly; for 3 weeks) restores skeletal growth, reduces mortality, and ameliorates achondroplasia-associated spinal, skull, and rib cage abnormalities in Fgfr3ach/+ mice[1].
Recifercept (0.25-2.5 mg/kg; s.c.; twice weekly; for 3 weeks) increases sternum and long bone growth in healthy wild-type mice without premature death or paralysis[1].
Recifercept (3-10 mg/kg; s.c.; twice weekly from PND3; 21 days) dose-dependently restores body weight, axial length, and long-bone growth in Fgfr3ach/+ mice[4].
Recifercept (10 mg/kg; s.c.; twice weekly; from postnatal day 3 for 3 weeks) prevents premature SOS ossification and improves skull phenotype in Fgfr3ach/+ achondroplasia mice[7].
Recifercept (10 mg/kg; s.c.; twice weekly; from postnatal day 3 for 3 weeks) does not alter the active SOS status in healthy wild-type mice[7].
Recifercept (0.25-2.5 mg/kg; s.c.; twice weekly; for 3 weeks) increases sternum and long bone growth in healthy wild-type mice without premature death or paralysis[1].
Recifercept (3-10 mg/kg; s.c.; twice weekly from PND3; 21 days) dose-dependently restores body weight, axial length, and long-bone growth in Fgfr3ach/+ mice[4].
Recifercept (10 mg/kg; s.c.; twice weekly; from postnatal day 3 for 3 weeks) prevents premature SOS ossification and improves skull phenotype in Fgfr3ach/+ achondroplasia mice[7].
Recifercept (10 mg/kg; s.c.; twice weekly; from postnatal day 3 for 3 weeks) does not alter the active SOS status in healthy wild-type mice[7].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:transgenic Fgfr3 ach/+ (Col2a1 promoter/enhancer; male and female; 3 days old at start)[1]
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Dosage:0.25 mg/kg; 2.5 mg/kg
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Administration:s.c.; twice per week; for 3 weeks
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Result:Mortality for vehicle-treated Fgfr3 ach/+ mice was 63%, compared with 20% at 0.25 mg/kg sFGFR3 and 12% at 2.5 mg/kg sFGFR3.
At day 22, alive Fgfr3 ach/+ pups numbered 36 in the 0.25 mg/kg group and 50 in the 2.5 mg/kg group; dead before day 22 numbered 9 and 7, respectively.
Causes of death in the 0.25 mg/kg group were respiratory failure (4) and paraplegia (5); in the 2.5 mg/kg group, respiratory failure (1) and paraplegia (6).
Treated transgenic mice had body and tail lengths that were not different from vehicle-treated wild-type controls.
Humerus, femurs, and tibiae from treated Fgfr3 ach/+ mice were longer than those from vehicle-treated transgenic mice and reached normal wild-type bone lengths.
Micro-computed tomography showed increased femoral cortical bone thickness in treated Fgfr3 ach/+ mice compared with vehicle-treated wild-type animals; trabecular bone thickness did not differ.
Histology showed hypertrophic chondrocytes in growth plates of treated Fgfr3 ach/+ mice, similar to vehicle-treated wild-type mice, with increased growth plate cartilage.
Sternum lengths in Fgfr3 ach/+ mice were 1.64 mm at 0.25 mg/kg (n = 36) and 1.82 mm at 2.5 mg/kg (n = 50).
Kyphosis was present in 17% of Fgfr3 ach/+ mice at 0.25 mg/kg and 6% at 2.5 mg/kg.
Immature C7 vertebrae were present in 29% at 0.25 mg/kg and 40% at 2.5 mg/kg; immature T11 vertebrae in 29% at 0.25 mg/kg and 0% at 2.5 mg/kg; lumbar compression in 18% at 0.25 mg/kg and 17% at 2.5 mg/kg.
Skull measurements for Fgfr3 ach/+ mice were: 0.25 mg/kg group width 10.1 mm, length 17.9 mm, L/W ratio 1.77; 2.5 mg/kg group width 10.3 mm, length 18.7 mm, L/W ratio 1.81.
Prevented premature closure of cranial synchondroses.
At 0.25 mg/kg, sFGFR3 increased body weight and length in Fgfr3 ach/+ mice to match vehicle-treated wild-type mice; at 2.5 mg/kg, treated dwarf mice were heavier and had longer long bones than vehicle-treated wild-type animals.
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Animal Model:wild-type littermates (male and female; 3 days old at start)[1]
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Dosage:0.25 mg/kg; 2.5 mg/kg
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Administration:s.c.; twice per week; for 3 weeks
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Result:No wild-type animals died prematurely or suffered paralysis.
Sternum lengths in wild-type mice were 1.83 mm at 0.25 mg/kg (n = 31) and 1.87 mm at 2.5 mg/kg (n = 47), compared with 1.72 mm in vehicle-treated wild-type mice (n = 67).
Also caused growth of long bones in wild-type mice.
Skull measurements for wild-type mice were: 0.25 mg/kg group width 10.5 mm, length 20.2 mm, L/W ratio 1.93; 2.5 mg/kg group width 10.6 mm, length 20.6 mm, L/W ratio 1.96; vehicle-treated wild-type group width 10.3 mm, length 20.0 mm, L/W ratio 1.94.
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Animal Model:Fgfr3ach/+ (G380R mutation)[3]
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Dosage:2.5 mg/kg
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Administration:s.c.; twice weekly; from day 3 to day 21/22 (6 injections during the growth period)
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Result:In Fgfr3ach/+ mice receiving sFGFR3:
At 4 weeks of age, animals receiving sFGFR3 displayed a 14.1% decrease in body weight compared to WT mice.
After 10 weeks of ND or HFD, sFGFR3 administration had no effect on body weight gain.
Significantly decreased abdominal lean:fat ratio in ND-fed mice, caused by decreased lean mass and increased fat mass; Fgfr3ach/+ mice receiving sFGFR3 displayed fat depot distributions similar to WT animals on ND and HFD.
After HFD, sFGFR3 administration restored subcutaneous adipocyte size and scattering and induced a slight increase in epididymal adipocyte size.
Adipokine array in Fgfr3ach/+ mice given 2.5 mg/kg sFGFR3: ND: pro-inflammatory +, obesity +, insulin pathway ++, FGF −; HFD: pro-inflammatory +, obesity ++, insulin pathway ++, FGF −.
Scale: − <2 A.U., + 10-30 A.U., ++ 30-100 A.U., +++ >100 A.U.
Restored glycemia and significantly increased insulin levels compared with control Fgfr3ach/+ mice.
When Fgfr3ach/+ mice were given 2.5 mg/kg sFGFR3, normal GTT responses were restored.
Pancreas islets, insulin, and glucagon contents were partially restored in animals receiving sFGFR3.
Restored a normal hepatic response; no hepatic nodules were observed.
Fgfr3ach/+ mice that received sFGFR3 during the growth period behaved like control WT mice after weaning under ND or HFD in indirect calorimetry.
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Animal Model:FVB (transgenic Fgfr3ach/+; cartilage-targeted expression of mutant FGFR3 driven by the Col2a1 promoter/enhancer; male and female)[4]
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Dosage:3 mg/kg; 10 mg/kg
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Administration:s.c.; twice weekly from PND3 (days 3, 5, 9, 11, 16, and 18); 21 days
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Result:Rescued body weight deficits of Fgfr3ach/+ mice to almost normal levels at 10 mg/kg.
Axial length was increased in the 10 mg/kg group compared with vehicle.
Recifercept had a dose-dependent effect on skeletal bone growth as seen in tibia, ulna, femur, and humerus measurements compared with vehicle.
Growth of these long bones reached normal level already at 3 mg/kg.
Representative skeletons at PND22 from Fgfr3ach/+ mice given Recifercept 3 mg/kg or 10 mg/kg showed improved overall skeletal growth relative to vehicle control Fgfr3ach/+ mice.
Recifercept was well tolerated without overt signs of adverse events.
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Animal Model:normally pigmented sable ferret (E33 and P6/P16)[6]
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Dosage:pCAG-sFGFR3 plasmid (with pCAG-EGFP)
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Administration:in utero electroporation into the lateral ventricle at E33; single administration
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Result:Severely impaired cortical folding.
The number of cortical neurons was reduced, with upper-layer (layers 2-4) neurons predominantly reduced.
S100β-positive cell number ratio in the suprasylvian gyrus (SSG): control 1.02 (n = 3 animals) versus sFGFR3 0.69 (n = 4 animals).
Vertical expansion ratio of the SP-OSVZ in gyri: control 0.84 (n = 3 animals) versus sFGFR3 0.29 (n = 3 animals).
ETV5 puncta number in astrocytes was greatly reduced by sFGFR3 (n = 3 animals per condition).
Caused a decrease in S100β-positive astrocytes in both upper and lower cortical layers.
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Animal Model:FVB (transgenic Fgfr3ach/+; human G380R mutation; age postnatal day 3 to day 22)[7]
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Dosage:10 mg/kg
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Administration:s.c.; twice weekly; from postnatal day 3 for 3 weeks
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Result:In Fgfr3ach/+ mice given Recifercept, SOS score distributions by X-ray were: PND3: score 0, 42.4%; score 1, 57.6%; score 2, 0%.
PND9: score 0, 39.4%; score 1, 60.6%; score 2, 0%.
PND22: score 0, 39.4%; score 1, 36.4%; score 2, 24.2%.
At PND22, 39.4% of Recifercept-administered Fgfr3ach/+ mice had score 0 synchondroses.
The proportion of score 0 synchondroses remained stable over time in Recifercept-administered Fgfr3ach/+ mice (42.4% at PND3, 39.4% at PND9, 39.4% at PND22).
At PND22, the proportion of score 0 synchondroses was higher with Recifercept than vehicle (39.4% and 12.5%, respectively).
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Animal Model:FVB (wild-type; age postnatal day 3 to day 22)[7]
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Dosage:10 mg/kg
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Administration:s.c.; twice weekly; from postnatal day 3 for 3 weeks
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Result:In WT mice given Recifercept, SOS score was 0 in 100% of animals at PND3, PND9, and PND22; score 1 and score 2 were 0% at all timepoints.
At PND22, 100% of synchondroses were active in WT animals.
Related Protocols :
- Kinase activity and phosphorylation assays
- Fibrosis/Collagen Morphometry
- Western Blot
- Collagen: Sirius Red Staining
- Research Protocol for Endocrine Diseases
- Connective Tissue: Masson's Trichrome/Collagen Trichrome Staining
- Protocol for Kinase activity and phosphorylation assays
- Research Protocol for Metabolic Diseases
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | 2011-05 | PHASE1 |
Conjugated
Unconjugated
Reconsititution
The product can be reconstituted/diluted with sterile PBS or saline.
Format
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FGFR3 (fibroblast growth factor receptor 3, ACH, achondroplasia, thanatophoric dwarfism, CEK2, CD333)Soluble
Chemical Information
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CAS No. 2226238-09-9
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Appearance Liquid
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Molecular Weight 37.72 kDa
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Color Colorless to light yellow
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SMILES
[Recifercept]
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Synonyms
TA-46; sFGFR3; PF-07256472
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Shipping
Shipping with dry ice.
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Formulation
Please refer to the lot-specific COA for specific buffer information.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
Select Batch:
Purity:
99.98%
Assay:
99.98%
ee.:
99.98%
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Data Sheet (293 KB)
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SDS (251 KB)
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- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
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- Portuguese - PT (251 KB)
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Inhibitory Antibodies User Guide (603 KB)
References
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Recifercept Related Classifications
HY-P99823 Related Classifications
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Keywords
- Recifercept
- 2226238-09-9
- TA-46
- sFGFR3
- PF-07256472
- TA46
- TA 46
- sFGFR3
- sFGFR 3
- sFGFR-3
- PF07256472
- PF 07256472
- PF-07256472
- FGFR
- p38 MAPK
- ERK
- FGF ligand
- FGFR3
- MAP-kinase
- PLCγ1
- achondroplasia
- chondrocyte
- extracellular matrix
- fibroblast-to-myofibroblast transition
- idiopathic pulmonary fibrosis
- visceral obesity
- Inhibitor
- inhibitor
- inhibit