Zimberelimab

• CAT Number: I043264
• CAS Number: 2259860-24-5
• Purity: ≥95%

Zimberelimab (GLS-010) is a fully human IgG4 anti-PD-1 monoclonal antibody with an EC50 of 210 pM for human PD-1. Zimberelimab effectively blocks the binding of PD-L1 and PD-L2 to cell-surface PD-1 in CHO-S cells, with IC50 values of 580 pM and 670 pM, respectively. Zimberelimab shows antitumor activities, and can be used for various cancers research, including cervical cancer, non-small cell lung cancer and classical Hodgkin’s lymphoma[1][2].
Zimberelimab has an EC50 of 210 pM for human PD-1 but does not bind to related CD28 family receptors, such as ICOS, CD28 and CTLA-4[1].
Zimberelimab binding to cell-expressed human PD-1 inhibits the interaction of the receptor with both human PD-L1 and PD-L2 with IC50s of 580 pM and 670 pM, respectively[1].
Zimberelimab dose-dependently enhances IFN-γ production and proliferation by CD4+ T cells, saturating at concentrations below 100 pM[1].
Zimberelimab (10 and 20 mg/kg; i.v.; BIW*3) shows significant anti-tumor effects in mice[2].
PK parameters of Zimberelimab after single vd administrations of 2, 6, and 18 mg/kg in cynomolgus macaques[2]

PK parameters
2 mg/kg
6 mg/kg
18 mg/kg

C0 (mg/mL)
103 ± 23.7 (23.0%)
157 ± 18.7 (11.9%)
508 ± 48.0 (9.46%)

T1/2 (h)
111 ± 23.7 (30.5%)
115 ± 32.8 (28.5%)
129 ± 17.0 (13.1%)

Vss (mL/kg)
48.4 ± 7.48 (15.5%)
49.4 ± 6.49 (13.1%)
46.3 ± 5.49 (11.8%)

Cl (mL/h/kg)
0.288 ± 0.0373 (13.0%)
0.278 ± 0.0308 (11.1%)
0.183 ± 0.0293 (16.0%)

Tlast (h)
396 ± 141 (35.5%)
704 ± 203 (28.9%)
816 ± 0.00

AUC0-last (h*mg/mL)
6300 ± 1320 (21.0%)
21300 ± 2570 (12.1%)
98100 ± 16300 (16.6%)

AUCo‑inf (h*mg/mL)
7060 ± 1020 (14.5%)
21800 ± 2310 (10.6%)
101000 ± 16700 (16.6%)

MRT0-last (h)
126 ± 23.3 (18.4%)
164 ± 31.2 (19.0%)
236 ± 14.8 (6.27%)

MRT0-inf (h)
170 ± 29.7 (17.5%)
180 ± 29.4 (16.4%)
255 ± 17.4 (6.82%)

AUC0-inf/AUC0-last (%)
113 ± 11.8 (10.4%)
103 ± 0.940 (0.916%)
103 ± 0.940 (0.916%)

C0, initial drug concentration; T1/2, half-life; Vss, apparent volume of distribution in the steady-state; Cl, clearance; Tlast, the last time; AUC, area under the curve; MRT, mean residence time.

Reference

[1]. Markham A. Zimberelimab: First Approval. Drugs. 2021 Nov;81(17):2063-2068.
 [Content Brief]

[2]. Lou B, et al. Preclinical Characterization of GLS-010 (Zimberelimab), a Novel Fully Human Anti-PD-1 Therapeutic Monoclonal Antibody for Cancer. Front Oncol. 2021 Sep 15;11:736955.
 [Content Brief]