ArticlemAbs
Design and characterization of MP0250, a tri-specific anti-HGF/anti-VEGF DARPin® drug candidate.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Peptide and Protein Tags for the Half-Life Extension of Therapeutic Agents: A Review Article.The protein journal · 2026Review
- Selection of the optimal chelator for labeling of DARPin Ec1 with gallium-68 for PET imaging of EpCAM expression.EJNMMI radiopharmacy and chemistry · 2025Article
- Targeting of Epithelial Cell Adhesion Molecule-Expressing Malignant Tumors Using an Albumin-Binding Domain-Fused Designed Ankyrin Repeat Protein: Effect of the Molecular Architecture.International journal of molecular sciences · 2025Article
- Article
- The present and future of bispecific antibodies for cancer therapy.Nature reviews. Drug discovery · 2024Review
- Impact of tissue penetration and albumin binding on design of T cell targeted bispecific agents.Neoplasia (New York, N.Y.) · 2024Article
- NSCLC: from tumorigenesis, immune checkpoint misuse to current and future targeted therapy.Frontiers in immunology · 2024Review
- Designing and computational analyzing of chimeric long-lasting GLP-1 receptor agonists for type 2 diabetes.Scientific reports · 2023Article
- Anti-Angiogenic Activity of Drugs in Multiple Myeloma.Cancers · 2023Review
- A potent and broad neutralization of SARS-CoV-2 variants of concern by DARPins.Nature chemical biology · 2023Article
- The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants.Nature biotechnology · 2022Article
- A Multi-Specific DARPin Potently Neutralizes Shiga Toxin 2 via Simultaneous Modulation of Both Toxin Subunits.Bioengineering (Basel, Switzerland) · 2022Article
- Current trends in biopharmaceuticals production in Escherichia coli.Biotechnology letters · 2022Review
- Deciphering albumin-directed drug delivery by imaging.Advanced drug delivery reviews · 2022Review
- Emerging Albumin-Binding Anticancer Drugs for Tumor-Targeted Drug Delivery: Current Understandings and Clinical Translation.Pharmaceutics · 2022Review
- Extending traditional antibody therapies: Novel discoveries in immunotherapy and clinical applications.Molecular therapy oncolytics · 2021Review
- Driving CARs with alternative navigation tools - the potential of engineered binding scaffolds.The FEBS journal · 2021Review
- Protease-stable DARPins as promising oral therapeutics.Protein engineering, design & selection : PEDS · 2021Article
- First-in-Human Phase I Study of MP0250, a First-in-Class DARPin Drug Candidate Targeting VEGF and HGF, in Patients With Advanced Solid Tumors.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Article
- Bi-paratopic and multivalent VH domains block ACE2 binding and neutralize SARS-CoV-2.Nature chemical biology · 2021Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MP0250 is a multi-domain drug candidate currently being tested in clinical trials for the treatment of cancer. It comprises one anti-vascular endothelial growth factor-A (VEGF-A), one anti-hepatocyte growth factor (HGF), and two anti-human serum albumin (HSA) DARPin® domains within a single polypeptide chain. While there is first clinical validation of a single-domain DARPin® drug candidate, little is known about DARPin® drug candidates comprising multiple domains. Here, we show that MP0250 can be expressed at 15 g/L in soluble form in E. coli high cell-density fermentation, it is stable in soluble/frozen formulation for 2 years as assessed by reverse phase HPLC, it has picomolar potency in inhibiting VEGF-A and HGF in ELISA and cellular assays, and its domains are simultaneously active as shown by surface plasmon resonance. The inclusion of HSA-binding DARPin® domains leads to a favorable pharmacokinetic profile in mouse and cynomolgus monkey, with terminal half-lives of ∼ 30 hours in mouse and ∼ 5 days in cynomolgus monkey. MP0250 is thus a highly potent drug candidate that could be particularly useful in oncology. Beyond MP0250, the properties of MP0250 indicate that multi-domain DARPin® proteins can be valuable next-generation drug candidates.
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