BT5528

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 modelIn VitroBT5528 shows high affinity on EphA2 with a K b value of 19.1 nM, and activates EphA2 in EphA2-expressing cells with an EC 50 value of 41.9 nM. BT5528 inhibits cancer cells growth with IC 50 s of 21.9 nM (HT-1080), 5.2 nM (PC-3), 21.6 nM (NCI-H1975), respectively. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoBT5528 (1, 2, 3 mg/kg; i.v.; once a week; 2-5 weeks) inhibits tumor growth in vivo in mice xenograft model . 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 . MCE has not independently confirmed the accuracy of these methods. They are for reference only. 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 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 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.Form:SolidIC50& Target:EC50: 41.9 nM (EphA2). Molecular Formula: C201H315N53O52S3. Molecular Weight: 4403.14. PubChem CID: 166177190. Isomeric SMILES: CC[C@@H](C)[C@H]([C@H](CC(=O)N1CCC[C@@H]1[C@H]([C@H](C)C(=O)N[C@@H](C)[C@@H](C2=CC=CC=C2)O)OC)OC)N(C)C(=O)[C@@H](C(C)C)NC(=O)[C@@H](C(C)C)N(C)C(=O)OCC3=CC=C(C=C3)NC(=O)[C@@H](CCCNC(=O)N)NC(=O)[C@@H](C(C)C)NC(=O)CCCC(=O)NCCC(=O)N(C)CC(=O)N(C)CC(=O)N(C)CC(=O)N(C)CC(=O)N(C)CC(=O)N(C)CC(=O)N(C)CC(=O)N(C)CC(=O)N(C)CC(=O)N(C)CC(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN=C(N)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H]4CSCCC(=O)N5CN6CN(C5)C(=O)CCSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]7CCCN7C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CSCCC6=O)NC(=O)[C@@H](NC(=O)[C@@H]8CCCN8C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]9C[C@H](CN9C4=O)O)CC(C)C)C(C)C)CC(=O)N)CC(C)C)CC(C)C)CC1=CNC=N1)CC(=O)O)CC1=CNC2=CC=CC=C21)CCCCN=C(N)N)C(=O)N.