Ponsegromab  (Synonyms: PF 06946860)

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^[1][2]. Ponsegromab acts as a chemosensitizer, increases intracellular reactive oxygen species, reduces glutathione levels^[1][2]. Ponsegromab can be used for the research of oxaliplatin-resistant colorectal cancer^[1][2].

Human IgG1 (L234A/L235A) kappa

Human IgG1 (L234A/L235A) kappa, Isotype Control

Human

GDF15/MIC1

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.

Ponsegromab (10 mg/kg; i.p.; twice weekly; until study endpoint) increases gastrocnemius muscle and epididymal fat weights in HT-1080 tumor-bearing NCG mice with cancer cachexia^[1].
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.

9518  [NCBI]

Q99988

ELISA, FACS, Functional assay

Unconjugated

The product can be reconstituted/diluted with sterile PBS or saline.

145.5 kDa

2368950-15-4

Liquid

Colorless to light yellow

[Ponsegromab]

Shipping with dry ice.

Please refer to the lot-specific COA for specific buffer information.

Please store the product under the recommended conditions in the Certificate of Analysis.

• 
  Human IgG1 kappa

• 
  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).

• [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]