BT1769 acetate is a conjugate and antitumor agent targeting MT1-MMP, with a K d value of 3.35 nM against human targets. BT1769 acetate exhibits favorable pharmacokinetic properties. BT1769 acetate specifically binds to MT1-MMP via its bicyclic peptide component, delivering the cytotoxic agent MMAE to antigen-expressing cells. It effectively inhibits tumor growth, induces complete responses, and significantly prolongs event-free survival in osteosarcoma patient-derived xenograft models. BT1769 acetate shows extremely low activity in Ewing sarcoma models and can be used in osteosarcoma-related research [1] [2].
In Vivo, BT1769 (acetate) (3.2 mg/kg; i.v.; once weekly) induces significant antitumor activity in HT1080 osteosarcoma xenografts in female BALB/c nude mice[2]. BT1769 (acetate) (3 mg/kg; i.v.; once weekly; 4 weeks) significantly prolongs event-free survival and induces maintained complete responses in most tested osteosarcoma patient-derived xenograft models in female CB17SC scid-/- mice[2].
In Vitro, BT1769 acetate (1.5625-100 nnM) binds to recombinant human MT1-MMP with a KD of 3.35 nM and to recombinant mouse MT1-MMP with a KD of 2.99 nM, showing high target affinity[2].
References:
[1]. Wang Y, et al. Abstract LB008: Integrative surfaceome profiling identifies immunotherapeutic targets in osteosarcomas (OS); Preclinical testing of BT1769, an MT1-MMP-targeted Bicycle Toxin Conjugate, in OS by the Pediatric Preclinical Testing Consortium (PPTC)[J]. Cancer Research, 2021, 81(13_Supplement): LB008-LB008.
[2]. Wang Y, et al. Comprehensive Surfaceome Profiling to Identify and Validate Novel Cell-Surface Targets in Osteosarcoma. Mol Cancer Ther. 2022;21(6):903-913.
In Vivo, BT1769 (acetate) (3.2 mg/kg; i.v.; once weekly) induces significant antitumor activity in HT1080 osteosarcoma xenografts in female BALB/c nude mice[2]. BT1769 (acetate) (3 mg/kg; i.v.; once weekly; 4 weeks) significantly prolongs event-free survival and induces maintained complete responses in most tested osteosarcoma patient-derived xenograft models in female CB17SC scid-/- mice[2].
In Vitro, BT1769 acetate (1.5625-100 nnM) binds to recombinant human MT1-MMP with a KD of 3.35 nM and to recombinant mouse MT1-MMP with a KD of 2.99 nM, showing high target affinity[2].
References:
[1]. Wang Y, et al. Abstract LB008: Integrative surfaceome profiling identifies immunotherapeutic targets in osteosarcomas (OS); Preclinical testing of BT1769, an MT1-MMP-targeted Bicycle Toxin Conjugate, in OS by the Pediatric Preclinical Testing Consortium (PPTC)[J]. Cancer Research, 2021, 81(13_Supplement): LB008-LB008.
[2]. Wang Y, et al. Comprehensive Surfaceome Profiling to Identify and Validate Novel Cell-Surface Targets in Osteosarcoma. Mol Cancer Ther. 2022;21(6):903-913.