Ponsegromab
Based on 3 publication(s) in Google Scholar
Ponsegromab is a Growth differentiation factor 15 (GDF15) inhibitor with human, cynomolgus monkey, and mouse target IC50 values of 0.123 nM, 0.053 nM, and 0.102 nM, respectively. Ponsegromab acts as a chemosensitizer, increases intracellular reactive oxygen species, reduces glutathione levels. Ponsegromab can be used for the research of oxaliplatin-resistant colorectal cancer.
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- Pureté: 99.60%
- CAS No.: 2368950-15-4
- Masse moléculaire:145.5 kDa
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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Publications Citing Use of MedChemExpress (MCE) Ponsegromab
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Activité biologique
Human IgG1 (L234A/L235A) kappa
Human
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GDF15 |
Ponsegromab (log concentrations from -4 to 2 nM; 1 h at 37 °C) potently inhibits the binding of human, cynomolgus monkey, and mouse GDF15 to GFRAL in cell-free ELISA assays with IC50 values of 0.123 nM, 0.053 nM, and 0.102 nM, respectively[1].
Ponsegromab (log concentrations from -4 to 1 nM; 17 h at 37 °C with 5% CO2) potently inhibits GDF15-GFRAL-RET-mediated ELK1 reporter activity in HEK293 cells with an IC50 of 0.037 nM[1].
Ponsegromab (log concentrations from -4 to 2 nM) potently inhibits GDF15-GFRAL-RET-mediated ERK1/2 phosphorylation in HEK293 cells with an IC50 of 0.051 nM[1].
Ponsegromab (log concentrations from -3 to 2 nM) potently inhibits GDF15-GFRAL-RET-mediated AKT phosphorylation in HEK293 cells with an IC50 of 0.171 nM[1].
Ponsegromab (10 µg/mL; 48 h) sensitizes LoVo-OxR and HCT-116-OxR oxaliplatin-resistant colorectal cancer cells to oxaliplatin, reducing oxaliplatin IC50 values to 8.176 μM and 7.818 μM, respectively[2].
Ponsegromab (10 µg/mL; 48 h) increases apoptosis in oxaliplatin-treated LoVo-OxR and HCT-116-OxR oxaliplatin-resistant colorectal cancer cells[2].
Ponsegromab (10 µg/mL; 48 h) modulates apoptosis-related protein expression in oxaliplatin-treated LoVo-OxR and HCT-116-OxR oxaliplatin-resistant colorectal cancer cells, reducing Bcl-2 and increasing cleaved caspase-3 levels[2].
Ponsegromab (10 µg/mL; 48 h) increases oxaliplatin-induced intracellular ROS levels in LoVo-OxR and HCT-116-OxR oxaliplatin-resistant colorectal cancer cells[2].
Ponsegromab (10 µg/mL; 48 h) reduces GSH levels and GSSG/GSH ratio in oxaliplatin-treated LoVo-OxR and HCT-116-OxR oxaliplatin-resistant colorectal cancer cells[2].
Ponsegromab (10 µg/mL; 48 h) reduces protein levels of Nrf2, NQO1, and HO-1 in LoVo-OxR and HCT-116-OxR oxaliplatin-resistant colorectal cancer cells[2].
Ponsegromab (10 µg/mL; 48 h) increases Nrf2 polyubiquitination and reduces Nrf2 interaction with β-TrCP in LoVo-OxR and HCT-116-OxR oxaliplatin-resistant colorectal cancer cells[2].
Ponsegromab (10 µg/mL; 48 h) increases the rate of Nrf2 protein degradation in HCT-116-OxR oxaliplatin-resistant colorectal cancer cells[2].
Ponsegromab (10 µg/mL; 2 h) reduces Nrf2 protein levels via the ubiquitin-proteasome pathway in LoVo-OxR and HCT-116-OxR oxaliplatin-resistant colorectal cancer cells, as MG132 treatment restores Nrf2 expression[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:LoVo-OxR, HCT-116-OxR (oxaliplatin-resistant human colorectal cancer cell lines)
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Concentration:10 µg/mL (in combination with oxaliplatin at 0, 2, 4, 8, 16, 32 μM)
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Incubation Time:48 h
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Result:Reduced the half-maximal inhibitory concentration (IC50) of oxaliplatin in LoVo-OxR cells from 14.290 μM to 8.176 μM, and in HCT-116-OxR cells from 19.650 μM to 7.818 μM, sensitizing the resistant cell lines to oxaliplatin treatment.
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Cell Line:LoVo-OxR, HCT-116-OxR (oxaliplatin-resistant human colorectal cancer cell lines)
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Concentration:10 µg/mL (in combination with 14.29 μM oxaliplatin for LoVo-OxR, 19.65 μM oxaliplatin for HCT-116-OxR)
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Incubation Time:48 h
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Result:Increased the proportion of apoptotic cells in oxaliplatin-treated LoVo-OxR and HCT-116-OxR cells, compared to oxaliplatin treatment alone.
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Cell Line:LoVo-OxR, HCT-116-OxR (oxaliplatin-resistant human colorectal cancer cell lines)
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Concentration:10 µg/mL (in combination with 14.29 μM oxaliplatin for LoVo-OxR, 19.65 μM oxaliplatin for HCT-116-OxR)
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Incubation Time:48 h
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Result:Reduced anti-apoptotic Bcl-2 protein levels and increased pro-apoptotic cleaved caspase-3 protein levels in oxaliplatin-treated LoVo-OxR and HCT-116-OxR cells.
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Cell Line:LoVo-OxR, HCT-116-OxR (oxaliplatin-resistant human colorectal cancer cell lines)
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Concentration:10 µg/mL
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Incubation Time:48 h
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Result:Reduced protein levels of Nrf2, as well as its downstream antioxidant target genes NQO1 and HO-1, in LoVo-OxR and HCT-116-OxR cells.\nIncreased polyubiquitination of Nrf2 and impaired the interaction between Nrf2 and β-TrCP (a ubiquitin ligase adapter) in LoVo-OxR and HCT-116-OxR cells.
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Cell Line:HCT-116-OxR (oxaliplatin-resistant human colorectal cancer cell line)
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Concentration:10 µg/mL
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Incubation Time:48 h (prior to cycloheximide chase over 60 min)
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Result:Increased the rate of Nrf2 protein degradation in HCT-116-OxR cells, reducing the half-life of Nrf2 protein compared to untreated control cells.
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Cell Line:LoVo-OxR, HCT-116-OxR (oxaliplatin-resistant human colorectal cancer cell lines)
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Concentration:10 µg/mL (in combination with 10 μM MG132)
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Incubation Time:2 h
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Result:Reduced Nrf2 protein levels in LoVo-OxR and HCT-116-OxR cells, and this inhibitory effect was reversed by MG132 treatment, restoring Nrf2 expression.
Ponsegromab (10 mg/kg; i.p.; once every 3 days; until study endpoint) restores body weight, increases ambulatory activity, partially normalizes respiratory exchange ratio, and increases heat production in HT-1080 tumor-bearing NCG mice with cancer cachexia[1].
Ponsegromab (10 mg/kg; i.p.; twice weekly; until study endpoint) partially reverses body weight loss in Renca tumor-bearing BALB/c mice with cancer cachexia[1].
Ponsegromab (10 mg/kg; i.p.; twice weekly; until study endpoint) partially reverses body weight loss in MC38-hGDF15 tumor-bearing C57BL/6 mice with cancer cachexia[1].
Ponsegromab (10 mg/kg; i.p.; once every 3 days; day 6 to day 21) maintains body weight, achieves 100% survival, restores gastrocnemius muscle weight, and partially restores epididymal fat weight in cisplatin-treated C57BL/6 mice with chemotherapy-induced cachexia[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NCG mice (6-week-old male; cancer cachexia model via subcutaneous HT-1080 human fibrosarcoma cell inoculation)[1]
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Dosage:10 mg/kg
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Administration:i.p.; twice weekly; until study endpoint
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Result:Increased gastrocnemius muscle weight; significantly increased epididymal fat weight compared to vehicle control.
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Animal Model:NCG mice (6-week-old male; cancer cachexia model via subcutaneous HT-1080 human fibrosarcoma cell inoculation)[1]
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Dosage:10 mg/kg
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Administration:i.p.; once every 3 days; until study endpoint
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Result:Restored lost body weight in cachectic mice; increased ambulatory activity compared to vehicle control; partially restored respiratory exchange ratio towards non-tumor bearing levels; increased heat production compared to vehicle control.
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Animal Model:BALB/c mice (6-week-old male; cancer cachexia model via subcutaneous Renca murine kidney tumor cell inoculation)[1]
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Dosage:10 mg/kg
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Administration:i.p.; twice weekly; until study endpoint
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Result:Led to partial recovery of body weight in cachectic mice, though body weight did not return to non-tumor bearing levels.
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Animal Model:C57BL/6 mice (6-week-old male; cancer cachexia model via subcutaneous MC38-hGDF15 murine colon cancer cell inoculation overexpressing human GDF15)[1]
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Dosage:10 mg/kg
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Administration:i.p.; twice weekly; until study endpoint
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Result:Led to partial recovery of body weight in cachectic mice, though body weight did not return to non-tumor bearing levels.
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Animal Model:C57BL/6 mice (6-week-old male; chemotherapy-induced cachexia model via cisplatin injection)[1]
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Dosage:10 mg/kg
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Administration:i.p.; once every 3 days; day 6 to day 21
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Result:Maintained body weight in cachectic mice (preventing continued weight loss seen in vehicle and isotype control groups), with endpoint body weight similar to normal untreated mice; achieved 100% survival to study endpoint; restored gastrocnemius muscle weight to normal levels; partially restored epididymal fat weight compared to vehicle control.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Unconjugated
The product can be reconstituted/diluted with sterile PBS or saline.
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Human IgG1 kappa
ELISA, FACS, Functional assay
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Immobilized GDF-15 Protein, Human (P.pastoris, His, HY-P75170) can bind Ponsegromab. The EC50 for this effect is 9.7 ng/mL. -
Flow Cytometry analysis of HepG2 cells with Ponsegromab (HY-P99241, red). Cells were fixed with 4% paraformaldehyde and permeabilised with 90% methanol. Then cells were stained with the primary antibody at 1/200 dilution for an hour at 4℃. Goat Anti-Human IgG H&L (AF488) (HY-P83776) was used as the secondary antibody at 1/1,000 dilution for 30 minutes at 4℃. Human IgG1 kappa (HY-P99001, blue) was used as the isotype control, cells without incubation with primary antibody were used as the unlabeled control (black).
Chemical Information
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CAS No. 2368950-15-4
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Appearance Liquid
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Masse moléculaire 145.5 kDa
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Color Colorless to light yellow
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SMILES
[Ponsegromab]
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Synonyms
PF 06946860
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Livraison
Shipping with dry ice.
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Formulation
Please refer to the lot-specific COA for specific buffer information.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Publications (3)
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Journal Impact Factor
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Most Recent
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bioRxiv
2024 Jun 17:2024.06.14.598891. PMID: 38948776
Pureté et documentation
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Fiche technique (273 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Inhibitory Antibodies User Guide (603 KB)
Références
[1]. Huang Y, et al. GB18-06, a nanobody targeting GDF15, effectively alleviates weight loss and restores physical function in cachexia models. MAbs. 2024;16(1):2416453. [Content Brief]
[2]. Lin H, et al. GDF15 induces chemoresistance to oxaliplatin by forming a reciprocal feedback loop with Nrf2 to maintain redox homeostasis in colorectal cancer. Cell Oncol (Dordr). 2024;47(4):1149-1165. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Ponsegromab Related Classifications
HY-P99241 Related Classifications
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