BI-836880 

BI-836880 is a humanized bispecific nanobody and a selective inhibitor of VEGF and ANG2, with a K_d of 16 pM for hANG2, an EC₅₀ of 1.4 nM for VEGF₁₆₅, and an EC₅₀ of 2.3 nM for VEGF₁₂₁. BI-836880 blocks ERK phosphorylation downstream of VEGF-A as well as TIE2 phosphorylation downstream of ANG2. BI-836880 does not inhibit ANG1-mediated TIE2 phosphorylation. BI-836880 exerts anti-angiogenic effects, reduces the number of immature endothelial vessels in tumor tissues, and inhibits tumor growth in preclinical models. BI-836880 can be used in the research of pancreatic cancer, non-small cell lung cancer, renal cell carcinoma, ovarian cancer, colon cancer, and Lewis lung cancer^[1].

VHH-VHH-VHH

Human

BI-836880 (0.4-500 nM) binds potently and selectively to hANG2 (K_D = 16 pM) and serum albumin (K_D = 9 nM) in cell-free surface plasmon resonance assays^[1].
BI-836880 binds selectively to hVEGF-A (EC₅₀ = 1.4 nM for VEGF₁₆₅, 2.3 nM for VEGF₁₂₁), and no binding to other VEGF family members or placental growth factor is detected in cell-free ELISA assays^[1].
BI-836880 potently blocks the binding of hANG2-TIE2 (IC₅₀ = 45-50 pM) and shows no activity against ANG1-TIE2 binding in cell-free assays^[1].
BI-836880 (0.16-20 nM; 5 min) potently inhibits VEGF-induced phosphorylation of ERK in human umbilical vein endothelial cells (HUVECs), with an IC₅₀ of 1.1-1.4 nM and an inhibition rate of 84-93%^[1].
BI-836880 (0.04-10.42 nM; 3 days) potently inhibits VEGF-induced proliferation of human umbilical vein endothelial cells (HUVEC), with an IC₅₀ of 0.6-0.8 nM and an inhibition rate of 84-93%^[1].
BI-836880 (following a 15-minute incubation) potently inhibits ANG2-induced TIE2 phosphorylation in TIE2-transfected HEK293 cells, with an IC₅₀ of 1.3-3.2 nM, and shows no activity against ANG1-induced TIE2 phosphorylation^[1].
BI-836880 (at log M concentrations ranging from -11 to -6; 72 h) completely inhibits ANG2-induced HUVEC survival in real-time impedance analysis, with an IC₅₀ of 1.9 nM^[1].

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

BI-836880 (13.7 mg/kg; i.p.; twice weekly; 2.5-9 weeks) exhibits significant antitumor activity across a panel of solid tumor xenograft models, with TGI values ranging from 51% to 92%, and demonstrates superior efficacy over single-pathway inhibitors Bevacizumab (HY-P9906) and AMG386 (HY-P99546) in multiple models^[1].
BI-836880 (15 mg/kg; i.p.; twice weekly; days 4 to 30) induces a 27% tumor growth inhibition (TGI) in the LL/2 syngeneic tumor model. Its combination with anti-PD-1 and VEGFR2 inhibition strategies increases TGI to 80%, while delaying tumor growth, improving tumor immune cell infiltration and promoting vascular normalization^[1].

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

7422  [NCBI] & 285  [NCBI]

P15692 & O15123

VEGFA & Ang2/ANGPT2/Angiopoietin2

ELISA, FACS, Functional assay

Unconjugated

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

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

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

• [1]. Hofmann I, et al. Pharmacodynamic and Antitumor Activity of BI 836880, a Dual Vascular Endothelial Growth Factor and Angiopoietin 2 Inhibitor, Alone and Combined with Programmed Cell Death Protein-1 Inhibition. J Pharmacol Exp Ther. 2023;384(3):331-342.  [Content Brief]