Tegoprubart  (Synonyms: AT-1501)

Tegoprubart (AT-1501) is a CD40 ligand inhibitor (EC₅₀=100 ng/mL) and immunosuppressant that selectively inhibits the CD40 ligand, a co-stimulatory molecule involved in T cell activation. Tegoprubart suppresses immune rejection, prevents rejection in animal transplantation models, and reduces cell-mediated and antibody-mediated immune responses to create a more immunotolerant environment. Tegoprubart preserves renal function when combined with Mycophenolate (HY-B0421) and Corticosteroids, and maintains graft function in preclinical studies. Tegoprubart is applicable to research related to kidney transplantation and kidney transplant rejection^[1].

Human IgG1 kappa

Human IgG1 kappa, Isotype Control

Human

The immune complex formed by Tegoprubart (600 nM; in vitro platelet activation assay) and soluble CD40L fails to induce PAC-1 expression on the surface of platelets from healthy individuals, does not trigger platelet aggregation, and exerts no platelet-activating effect; in contrast, the immune complex formed by Hu5C8 (HY-P99315) and soluble CD40L significantly induces platelet aggregation^[1].
Tegoprubart (2 μg/mL; 1 h; CD40L binding assay) exhibits binding affinity to recombinant human CD40L comparable to that of Hu5C8, with both antibodies having an EC₅₀ value of 100 ng/mL^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Tegoprubart (25 mg/kg; intravenous injection; once on days -1, 0, 3, 10, 18, 23, and 28 post-surgery, followed by once every 14 days; for 182 days) enables partial animals to maintain islet graft function up to day 182, improves glycated hemoglobin (% A1C), and causes no thromboembolic events in a cynomolgus monkey (Macaca fascicularis) model of intrahepatic islet allotransplantation^[1].
In the cynomolgus monkey intrahepatic islet allotransplantation model, tegoprubart (25 mg/kg; intravenous injection; once on days -2, -1, 0, 1, 3, 7, 10, 18, 23, and 28 post-operation, then once every 14 days thereafter; for 182 days), when combined with thymoglobulin (5 mg/kg, intravenous injection on days -2, -1, 0, 1, and 2 post-operation), rapamycin, and anti-TNF-α, maintains islet graft function, enables insulin independence in some animals, and causes no severe cytomegalovirus (CMV) reactivation^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

959  [NCBI]

P29965

ELISA, FACS, Functional assay

Unconjugated

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

145.56 kDa

2628092-47-5

Liquid

Colorless to light yellow

[Tegoprubart]

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 CD40L/CD154/TRAP Protein, Human (His, HY-P72907) can bind Tegoprubart. The EC₅₀ for this effect is 4.211 ng/mL.
• 
  Flow cytometric analysis of 1X10⁶ 500 ng/mL anti-CD3 stimulated Jurkat cells(24h) with Tegoprubart (HY-P990083, red). Cells were fixed with 4% paraformaldehyde. Then stained with the primary antibody at 1/200 dilution for an hour at 4℃. Alexa Fluor 488-conjugated AffiniPure Goat Anti-Human IgG H&L (HY-P83776) was used as the secondary antibody at 1/1,000 dilution for 30 minutes at 4℃. Human IgG1 kappa Isotype Control (HY-P99001, blue) was used as the isotype control, cells without incubation with primary antibody were used as the unlabeled control (black).
• 
  Loaded Tegoprubart on ProA biosensor, can bind CD40L/CD154/TRAP Protein, Human (HY-P7144) with an affinity constant of 4.923E-10 M as determined in BLI assay.

• [1]. Anwar IJ, et al. The anti-CD40L monoclonal antibody AT-1501 promotes islet and kidney allograft survival and function in nonhuman primates. Sci Transl Med. 2023 Aug 30;15(711):eadf6376.  [Content Brief]