التفاصيل البيبلوغرافية
| العنوان: |
In Vivo Half-Life Extension of BMP1/TLL Metalloproteinase Inhibitors Using Small-Molecule Human Serum Albumin Binders |
| المؤلفون: |
Julien C. Vantourout (9461890), Andrew M. Mason (2119783), Josephine Yuen (2485606), Graham L. Simpson (1523503), Ghotas Evindar (1370346), Letian Kuai (1264671), Michael Hobbs (7401971), Emma Edgar (5894981), Saul Needle (10063482), Xiaopeng Bai (2643814), Steve Wilson (71342), Paul Scott-Stevens (6321608), William Traylen (10063485), Kim Lambert (10063488), Neil Young (3413366), Shenaz Bunally (10063491), Scott G. Summerfield (3005832), Richard Snell (10063494), Rakesh Lad (10063497), Eric Shi (2504092), Steven Skinner (1971115), Lisa Shewchuk (1523839), Allan J.B. Watson (10063500), Chun-wa Chung (1343454), Sandeep Pal (1954993), Dennis A. Holt (3024240), Lara S. Kallander (1523863), Joanne Prendergast (5475158), Katrina Rivera (4419814), David G. Washburn (2989575), Mark R. Harpel (345389), Christopher Arico-Muendel (1665247), Albert Isidro-Llobet (1369611) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biochemistry, Medicine, Cell Biology, Molecular Biology, Pharmacology, Biotechnology, Cancer, Mental Health, Hematology, Chemical Sciences not elsewhere classified, small-molecule noncovalent HSA binder, vivo half-life, AlbuBinder 1, conjugate, half-live, BMP, half-life extension technologies, Vivo Half-Life Extension, KI, Small-Molecule Human Serum Albumin ., half-life extension |
| الوصف: |
Reducing the required frequence of drug dosing can improve the adherence of patients to chronic treatments. Hence, drugs with longer in vivo half-lives are highly desirable. One of the most promising approaches to extend the in vivo half-life of drugs is conjugation to human serum albumin (HSA). In this work, we describe the use of AlbuBinder 1 , a small-molecule noncovalent HSA binder, to extend the in vivo half-life and pharmacology of small-molecule BMP1/TLL inhibitors in humanized mice (HSA KI/KI). A series of conjugates of AlbuBinder 1 with BMP1/TLL inhibitors were prepared. In particular, conjugate c showed good solubility and a half-life extension of >20-fold versus the parent molecule in the HSA KI/KI mice, reaching half-lives of >48 h with maintained maximal inhibition of plasma BMP1/TLL. The same conjugate showed a half-life of only 3 h in the wild-type mice, suggesting that the half-life extension was principally due to specific interactions with HSA. It is envisioned that conjugation to AlbuBinder 1 should be applicable to a wide range of small molecule or peptide drugs with short half-lives. In this context, AlbuBinders represent a viable alternative to existing half-life extension technologies. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| العلاقة: |
https://figshare.com/articles/journal_contribution/_i_In_Vivo_i_Half-Life_Extension_of_BMP1_TLL_Metalloproteinase_Inhibitors_Using_Small-Molecule_Human_Serum_Albumin_Binders/13681329Test |
| DOI: |
10.1021/acs.bioconjchem.0c00662.s001 |
| الإتاحة: |
https://doi.org/10.1021/acs.bioconjchem.0c00662.s001Test |
| حقوق: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.8AC1331D |
| قاعدة البيانات: |
BASE |
