Povetacicept  (Synonyms: ALPN-303)

Povetacicept (ALPN-303) is an engineered Fc fusion protein containing the TACI domain, and acts as a dual APRIL/BAFF antagonist. The K_d value of Povetacicept for human BAFF is 59.3 pM, while its K_d value for human APRIL is 1.00 pM. Povetacicept reduces the activation, proliferation, differentiation and survival of B cells, and inhibits the production of immunoglobulins and autoantibodies. Povetacicept can be used in research related to autoimmune hemolytic anemia, immune thrombocytopenia, systemic lupus erythematosus, lupus nephritis and myasthenia gravis^[1][2][3].

TNFSF13B

Povetacicept (0.137-33.3 nM; 240-1800 s) binds recombinant human APRIL with a K_d of 1.00 pM and recombinant human BAFF with a K_d of 59.3 pM, demonstrating high-affinity dual binding to both cytokines^[2].
Povetacicept (2.5 pM-200 nM; 20 min pre-incubation, 5 h cell incubation) potently inhibits APRIL, BAFF, BAFF 60-mer, and BAFF/APRIL heterotrimer signaling in TACI/Jurkat/NF-κB reporter cells, with inhibitory activity superior to WT TACI-Fc proteins, anti-APRIL monoclonal antibodies, belimumab, and telitacicept^[2].
Povetacicept (4 d incubation; 3 d pre-stimulation) potently inhibits primary human B cell proliferation, differentiation of class-switched memory B cells and plasma cells, and immunoglobulin secretion, with activity superior to telitacicept, anti-APRIL monoclonal antibodies, and anti-BAFF monoclonal antibodies^[2].

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

Povetacicept (10 mg/kg; i.p.; twice weekly; 3.5 weeks) significantly reduces bone marrow antibody-secreting cell counts, suppresses autoantibody production, and increases hematocrit in an HOD⁺OTII⁺ mouse model of AIHA^[1].
Povetacicept (15 mg/kg; i.p.; 2 doses (days 4 and 11)) potently reduces splenic immune cell subsets and inhibits T cell-dependent antibody formation more effectively than WT TACI-Fc comparators in KLH-immunized mice^[2].
Povetacicept (10 mg/kg; i.p.; 2 doses (days 1 and 6)) exhibits superior immunosuppressive activity over single-target inhibitors, combination therapy, telitacicept, and anti-CD20 in SRBC-immunized mice, leading to greater suppression of T cell-dependent antibody responses^[2].
Povetacicept (17 mg/kg; i.p.; twice weekly; 20 weeks) significantly suppresses lupus disease activity, improves survival, and reduces renal and glandular pathology in the spontaneous NZB/NZW F1 lupus mouse model^[2].
Povetacicept (10 mg/kg; i.p.; twice weekly; day 5 to day 88) significantly suppresses renal immune deposition and reduces pathogenic splenic immune cell subsets in the inducible bm12 lupus mouse model^[2].

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

ELISA, FACS, Functional assay

Unconjugated

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

62.61 kDa

2490217-42-8

Liquid

Colorless to light yellow

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.

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  FPIA_[PROTEIN_1REPEAT]2-FC

• [1]. Stacey Dillon, et al. Povetacicept (ALPN-303; TACI vTD-Fc), an enhanced, potent dual inhibitor of BAFF and APRIL, ameliorates experimental autoimmune myasthenia gravis in C57BL/6N mice. Front. Immunol., 06 June 2025.

  [2]. Evans LS, et al. Povetacicept, an Enhanced Dual APRIL/BAFF Antagonist That Modulates B Lymphocytes and Pathogenic Autoantibodies for the Treatment of Lupus and Other B Cell-Related Autoimmune Diseases. Arthritis Rheumatol. 2023;75(7):1187-1202.  [Content Brief]

  [3]. Rinaldi E, et al. Povetacicept (ALPN-303; TACI vTD-Fc), an enhanced, potent dual inhibitor of BAFF and APRIL, ameliorates experimental autoimmune myasthenia gravis in C57BL/6N mice. Front Immunol. 2025;16:1533093. Published 2025 Jun 6.  [Content Brief]