| Description |
BT5528 is a bicyclic peptide toxin conjugate, an EphA2 activator. BT5528, made up of a bicyclic peptide and Auristatin E (HY-15582), is derivated from BCY6099. BT5528 shows potent anti-tumor activity without bleeding or coagulation toxicity in rats model[1][2].
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| Related Catalog |
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| Target |
EC50: 41.9 nM (EphA2)[1]
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| In Vitro |
BT5528 shows high affinity on EphA2 with a Kb value of 19.1 nM, and activates EphA2 in EphA2-expressing cells with an EC50 value of 41.9 nM[1]. BT5528 inhibits cancer cells growth with IC50s of 21.9 nM (HT-1080), 5.2 nM (PC-3), 21.6 nM (NCI-H1975), respectively[1].
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| In Vivo |
BT5528 (1, 2, 3 mg/kg; i.v.; once a week; 2-5 weeks) inhibits tumor growth in vivo in mice xenograft model[1]. BT5528 (3 mg/kg; i.v.; once a week; 3 weeks) exhibits greate ability to penetrate solid tumours in Non-small-cell lung carcinoma (NSCLC) Patient-derived xenograft (PDX) xenograft model in mice[1]. Animal Model: Xenograft model in mice with NCI-H1975 Non-small cell lung cancer, MDA-MB-231 Triple-negative breast cancer, MOLP-8 Multiple Myeloma[1] Dosage: 1, 2, 3 mg/kg Administration: Intravenous injection; once a week; for 5, 3, 2 weeks respectively Result: Showed target-mediated efficacy in the high EphA2-expressing NCI-H1975 NSCLC xenograft and MDA-MB-231 TNBC xenograft, but there were no significant effects in the low EphA2-expressing MOLP-8 Multiple Myeloma xenograft. Animal Model: Non-small-cell lung carcinoma (NSCLC) Patient-derived xenograft (PDX) xenograft model in mice[1] Dosage: 3 mg/kg; compared with MEDI 547 (3 mg/kg) Administration: Intravenous injection; once a week; for 3-4 weeks Result: Maintained efficacy during 3 weeks, while MEDI-547 fails to show efficacy. Didn’t affect D-Dimer, APTT or liver enzyme parameters.
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| References |
[1]. Bennett G, et al. Abstract 5854: bt5528, a bicycle toxin conjugate targeting epha2 has potent anti-tumor activity without bleeding or coagulation abnormalities in preclinical models. Cancer Research. 2018. 78(13 Supplement), 5854-5854. [2]. Bennett G, et al. MMAE Delivery Using the Bicycle Toxin Conjugate BT5528. Mol Cancer Ther. 2020 Jul;19(7):1385-1394.
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