更新于：2024-11-01

OXA1L x albumin

更新于：2024-11-01

基本信息

关联

项与 OXA1L x albumin 相关的药物

CN116836296

专利挖掘

靶点

OXA1L x albumin

作用机制-

在研机构

兰州大学

原研机构

兰州大学

在研适应症

情绪障碍 [+1]

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 OXA1L x albumin 相关的临床结果

登录后查看更多信息

100 项与 OXA1L x albumin 相关的转化医学

登录后查看更多信息

0 项与 OXA1L x albumin 相关的专利（医药）

登录后查看更多信息

2,017

项与 OXA1L x albumin 相关的文献（医药）

2024-12-31·mAbs

Characterization of the bispecific VHH antibody tarperprumig (ALXN1820) specific for properdin and designed for low-volume administration

Article

作者: Hunter, Todd ; Andersen, Gregers Rom ; Hunter, Jeffrey ; Pedersen, Dennis Vestergaard ; Patel, Rekha ; Sun, Fang ; Tamburini, Paul ; Devore, Denise ; Cone, Josh

The bispecific antibody tarperprumig (ALXN1820) was developed as a treatment option for diseases involving dysregulated complement alternative pathway (AP) activity that could be administered in small volumes, either subcutaneously or intravenously. Tarperprumig incorporates a C-terminal variable domain of a heavy chain only antibody (VHH) that binds properdin (FP) connected via a flexible linker to an N-terminal VHH that binds human serum albumin (HSA). The purified bispecific VHH antibody exhibits an experimental molecular weight average of 27.4 kDa and can be formulated at > 100 mg/mL. Tarperprumig binds tightly to FP and HSA with sub-nanomolar affinity at pH 7.4 and can associate simultaneously with FP and HSA to form a ternary complex. Tarperprumig potently and dose-dependently inhibits to completion in vitro AP-dependent complement C5b-9 formation, AP-dependent hemolysis, and the AP deposition of C3, FP and C9. X-ray crystallography revealed that the isolated FP-binding VHH recognizes the thrombospondin repeat 5 domain of FP, thereby preventing FP from binding to the AP convertase owing to severe steric hindrance. Tarperprumig cross-reacts with cynomolgus monkey FP and serum albumin. In summary, tarperprumig exhibits properties tailored for subcutaneous administration and is currently in clinical development for the treatment of complement AP-related disorders.

2024-12-01·Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

Spectroscopic study on volasertib: Highly stable complexes with albumin and encapsulation into alginate/montmorillonite bionanocomposites

Article

作者: Bravo, Iván ; Herrera-Ochoa, Diego ; Garzón-Ruiz, Andrés ; Darder, Margarita ; Pacheco-Liñán, Pedro J ; Albaladejo, José ; Fernández-Sainz, Jesús

In the present work, we study different physicochemical properties related to LADME processes of volasertib, a Polo-like kinase 1 inhibitor in advanced clinical trials. Firstly, the protonation equilibria, the extent of ionization at the physiological pH and pK_a values of this drug are studied combining spectroscopic techniques and computational calculations. Secondly, the binding process of volasertib to the human serum albumin (HSA) protein is analyzed by fluorescence spectroscopy. We report a high binding constant to HSA (K_a = 4.10 × 10⁶ M^-1) and their pharmacokinetic implications are discussed accordingly. The negative enthalpy and entropy (ΔH⁰ = -54.49 kJ/mol; ΔS⁰ = -58.90 J K^-1 mol^-1) determined for the binding process suggests the implication of hydrogen bonds and van der Waals interactions in the formation of the HSA-volasertib complex. Additionally, volasertib is encapsulated in an alginate/montmorillonite bionanocomposite as a proof of concept for an oral delivery nanocarrier. The physical properties of that nanocomposite as well as volasertib delivery kinetics are analyzed.

2024-12-01·Chemico-Biological Interactions

Binding characteristics of the major kratom alkaloid, mitragynine, towards serum albumin: Spectroscopic, calorimetric, microscopic, and computational investigations

Article

作者: Bakar, Khairul Azreena ; Lam, Su Datt ; Feroz, Shevin Rizal

Mitragynine (MTG) is a prominent indole alkaloid that is present abundantly in Mitragyna speciosa, commonly referred to as kratom. MTG has garnered significant attention due to its selective agonistic characteristics towards opioid receptors and related analgesic effects. In the circulatory system, the in vivo efficacy of MTG is dictated by its interaction with plasma proteins, primarily human serum albumin (HSA). In the present study, we utilized a broad methodology that included spectroscopic, calorimetric, microscopic, and in silico approaches to characterize the interaction between MTG and HSA. Alterations in the UV absorption spectrum of HSA by the presence of MTG demonstrated a ground-state complexation between the protein and the ligand. The K_a values obtained for the MTG-HSA interaction were in the range 10³-10⁴ M^-1 based on analysis of fluorescence and ITC data, respectively, indicating an intermediate binding affinity. The binding reaction was thermodynamically favorable as revealed by ΔH, ΔS, and ΔG values of -16.42 kJ mol^-1, 39.97 J mol^-1 K^-1, and -28.34 kJ mol^-1, respectively. Furthermore, CD spectroscopy results suggested MTG binding induced minimal effects on the structural integrity of HSA, supported by computational methods. Changes in the dimensions of HSA particles due to aggregation, as observed using atomic force microscopy in the presence of MTG. Competitive drug displacement results seemingly suggested site III of HSA located at subdomain IB as the preferred binding site of MTG, but were in inconclusive. However, docking results showed the clear preference of MTG to bind to site III, facilitated by hydrophobic (alkyl and pi-alkyl) and van der Waals forces, together with carbon hydrogen bonds. Additionally, the MTG-HSA complexation was demonstrated to be stable based on molecular dynamics analysis. The outcomes of this study shed light on the therapeutic potential of MTG and can help in the design of more effective derivatives of the compound.