Gantenerumab

DB12034

biotech investigational

Deskripsi

Alzheimer's disease (AD) is the most common cause of dementia in elderly patients, with classical histopathological hallmarks including extracellular amyloid-beta (A?) plaques and intraneuronal neurofibrillary tangles (NFTs). As the classical view of AD pathology posits that A? accumulation triggers tau hyperphosphorylation and aggregation to form NFTs and cause neurodegeneration, large efforts have gone into developing treatments to reduce A? aggregation and remove A? plaques.A244705, A244710 These treatments include the related antibodies aducanumab, which has been granted accelerated FDA approval, along with bapineuzumab, crenezumab, donanemab, lecanemab, and solanezumab, which are at varying stages of clinical development. Despite the clear association of A? aggregation with AD, treatments aimed at preventing A? aggregation or removing pre-existing A? plaques have shown little to no clinical benefit thus far and remain controversial.A244705, A244710, A244745

Gantenerumab is a fully human IgG1? monoclonal antibody derived from the MorphoSys HuCAL®-Fab1 phage display library and subsequently optimized by in vitro CDR cassette exchange. Gantenerumab binds to a unique A? epitope compared to other anti-A? antibodies and preferentially recognizes A? oligomers and fibrils over monomers.A244720

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) Gantenerumab administered as a single 300 mg subcutaneous injection in healthy volunteers over five or 15 seconds yielded a mean half-life of 22 or 21 days, respectively.[A244740]
Volume Distribusi -
Klirens (Clearance) -

Absorpsi

Gantenerumab administered as a single 300 mg subcutaneous injection in healthy volunteers over five or 15 seconds yielded a median Tmax of 119 hours (roughly five days).A244740 Only ~1% of administered gantenerumab crosses the blood-brain barrier, such that at 1200 mg doses given subcutaneously, peak brain steady-state exposure is reached in approximately five months.A244745

Metabolisme

Data metabolisme tidak tersedia.

Rute Eliminasi

Data eliminasi belum tersedia.

Interaksi Obat

373 Data
Diethylstilbestrol Diethylstilbestrol may increase the thrombogenic activities of Gantenerumab.
Chlorotrianisene Chlorotrianisene may increase the thrombogenic activities of Gantenerumab.
Conjugated estrogens Conjugated estrogens may increase the thrombogenic activities of Gantenerumab.
Estrone Estrone may increase the thrombogenic activities of Gantenerumab.
Estradiol Estradiol may increase the thrombogenic activities of Gantenerumab.
Dienestrol Dienestrol may increase the thrombogenic activities of Gantenerumab.
Ethinylestradiol Ethinylestradiol may increase the thrombogenic activities of Gantenerumab.
Mestranol Mestranol may increase the thrombogenic activities of Gantenerumab.
Estriol Estriol may increase the thrombogenic activities of Gantenerumab.
Estrone sulfate Estrone sulfate may increase the thrombogenic activities of Gantenerumab.
Quinestrol Quinestrol may increase the thrombogenic activities of Gantenerumab.
Hexestrol Hexestrol may increase the thrombogenic activities of Gantenerumab.
Tibolone Tibolone may increase the thrombogenic activities of Gantenerumab.
Synthetic Conjugated Estrogens, A Synthetic Conjugated Estrogens, A may increase the thrombogenic activities of Gantenerumab.
Synthetic Conjugated Estrogens, B Synthetic Conjugated Estrogens, B may increase the thrombogenic activities of Gantenerumab.
Polyestradiol phosphate Polyestradiol phosphate may increase the thrombogenic activities of Gantenerumab.
Esterified estrogens Esterified estrogens may increase the thrombogenic activities of Gantenerumab.
Zeranol Zeranol may increase the thrombogenic activities of Gantenerumab.
Equol Equol may increase the thrombogenic activities of Gantenerumab.
Promestriene Promestriene may increase the thrombogenic activities of Gantenerumab.
Methallenestril Methallenestril may increase the thrombogenic activities of Gantenerumab.
Epimestrol Epimestrol may increase the thrombogenic activities of Gantenerumab.
Moxestrol Moxestrol may increase the thrombogenic activities of Gantenerumab.
Estradiol acetate Estradiol acetate may increase the thrombogenic activities of Gantenerumab.
Estradiol benzoate Estradiol benzoate may increase the thrombogenic activities of Gantenerumab.
Estradiol cypionate Estradiol cypionate may increase the thrombogenic activities of Gantenerumab.
Estradiol valerate Estradiol valerate may increase the thrombogenic activities of Gantenerumab.
Biochanin A Biochanin A may increase the thrombogenic activities of Gantenerumab.
Formononetin Formononetin may increase the thrombogenic activities of Gantenerumab.
Estetrol Estetrol may increase the thrombogenic activities of Gantenerumab.
Cetuximab The risk or severity of adverse effects can be increased when Cetuximab is combined with Gantenerumab.
Human immunoglobulin G The risk or severity of adverse effects can be increased when Human immunoglobulin G is combined with Gantenerumab.
Omalizumab The risk or severity of adverse effects can be increased when Omalizumab is combined with Gantenerumab.
Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Gantenerumab.
Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Gantenerumab.
Gemtuzumab ozogamicin The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Gantenerumab.
Indium In-111 satumomab pendetide The risk or severity of adverse effects can be increased when Indium In-111 satumomab pendetide is combined with Gantenerumab.
Infliximab The risk or severity of adverse effects can be increased when Infliximab is combined with Gantenerumab.
Trastuzumab The risk or severity of adverse effects can be increased when Trastuzumab is combined with Gantenerumab.
Rituximab The risk or severity of adverse effects can be increased when Rituximab is combined with Gantenerumab.
Basiliximab The risk or severity of adverse effects can be increased when Basiliximab is combined with Gantenerumab.
Muromonab The risk or severity of adverse effects can be increased when Muromonab is combined with Gantenerumab.
Digoxin Immune Fab (Ovine) The risk or severity of adverse effects can be increased when Digoxin Immune Fab (Ovine) is combined with Gantenerumab.
Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Gantenerumab.
Tositumomab The risk or severity of adverse effects can be increased when Tositumomab is combined with Gantenerumab.
Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Gantenerumab.
Capromab pendetide The risk or severity of adverse effects can be increased when Capromab pendetide is combined with Gantenerumab.
Efalizumab The risk or severity of adverse effects can be increased when Efalizumab is combined with Gantenerumab.
Antithymocyte immunoglobulin (rabbit) The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Gantenerumab.
Natalizumab The risk or severity of adverse effects can be increased when Natalizumab is combined with Gantenerumab.
Palivizumab The risk or severity of adverse effects can be increased when Palivizumab is combined with Gantenerumab.
Daclizumab The risk or severity of adverse effects can be increased when Daclizumab is combined with Gantenerumab.
Bevacizumab The risk or severity of adverse effects can be increased when Bevacizumab is combined with Gantenerumab.
Technetium Tc-99m arcitumomab The risk or severity of adverse effects can be increased when Technetium Tc-99m arcitumomab is combined with Gantenerumab.
Eculizumab The risk or severity of adverse effects can be increased when Eculizumab is combined with Gantenerumab.
Panitumumab The risk or severity of adverse effects can be increased when Panitumumab is combined with Gantenerumab.
Ranibizumab The risk or severity of adverse effects can be increased when Ranibizumab is combined with Gantenerumab.
Galiximab The risk or severity of adverse effects can be increased when Galiximab is combined with Gantenerumab.
Pexelizumab The risk or severity of adverse effects can be increased when Pexelizumab is combined with Gantenerumab.
Afelimomab The risk or severity of adverse effects can be increased when Afelimomab is combined with Gantenerumab.
Epratuzumab The risk or severity of adverse effects can be increased when Epratuzumab is combined with Gantenerumab.
Bectumomab The risk or severity of adverse effects can be increased when Bectumomab is combined with Gantenerumab.
Oregovomab The risk or severity of adverse effects can be increased when Oregovomab is combined with Gantenerumab.
IGN311 The risk or severity of adverse effects can be increased when IGN311 is combined with Gantenerumab.
Adecatumumab The risk or severity of adverse effects can be increased when Adecatumumab is combined with Gantenerumab.
Labetuzumab The risk or severity of adverse effects can be increased when Labetuzumab is combined with Gantenerumab.
Matuzumab The risk or severity of adverse effects can be increased when Matuzumab is combined with Gantenerumab.
Fontolizumab The risk or severity of adverse effects can be increased when Fontolizumab is combined with Gantenerumab.
Bavituximab The risk or severity of adverse effects can be increased when Bavituximab is combined with Gantenerumab.
CR002 The risk or severity of adverse effects can be increased when CR002 is combined with Gantenerumab.
Rozrolimupab The risk or severity of adverse effects can be increased when Rozrolimupab is combined with Gantenerumab.
Girentuximab The risk or severity of adverse effects can be increased when Girentuximab is combined with Gantenerumab.
Obiltoxaximab The risk or severity of adverse effects can be increased when Obiltoxaximab is combined with Gantenerumab.
XTL-001 The risk or severity of adverse effects can be increased when XTL-001 is combined with Gantenerumab.
NAV 1800 The risk or severity of adverse effects can be increased when NAV 1800 is combined with Gantenerumab.
Briakinumab The risk or severity of adverse effects can be increased when Briakinumab is combined with Gantenerumab.
Otelixizumab The risk or severity of adverse effects can be increased when Otelixizumab is combined with Gantenerumab.
AMG 108 The risk or severity of adverse effects can be increased when AMG 108 is combined with Gantenerumab.
Iratumumab The risk or severity of adverse effects can be increased when Iratumumab is combined with Gantenerumab.
Enokizumab The risk or severity of adverse effects can be increased when Enokizumab is combined with Gantenerumab.
Ramucirumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Gantenerumab.
Farletuzumab The risk or severity of adverse effects can be increased when Farletuzumab is combined with Gantenerumab.
Veltuzumab The risk or severity of adverse effects can be increased when Veltuzumab is combined with Gantenerumab.
Ustekinumab The risk or severity of adverse effects can be increased when Ustekinumab is combined with Gantenerumab.
Trastuzumab emtansine The risk or severity of adverse effects can be increased when Trastuzumab emtansine is combined with Gantenerumab.
PRO-542 The risk or severity of adverse effects can be increased when PRO-542 is combined with Gantenerumab.
TNX-901 The risk or severity of adverse effects can be increased when TNX-901 is combined with Gantenerumab.
Inotuzumab ozogamicin The risk or severity of adverse effects can be increased when Inotuzumab ozogamicin is combined with Gantenerumab.
RI 624 The risk or severity of adverse effects can be increased when RI 624 is combined with Gantenerumab.
Stamulumab The risk or severity of adverse effects can be increased when MYO-029 is combined with Gantenerumab.
CT-011 The risk or severity of adverse effects can be increased when CT-011 is combined with Gantenerumab.
Leronlimab The risk or severity of adverse effects can be increased when Leronlimab is combined with Gantenerumab.
Glembatumumab vedotin The risk or severity of adverse effects can be increased when Glembatumumab vedotin is combined with Gantenerumab.
Olaratumab The risk or severity of adverse effects can be increased when Olaratumab is combined with Gantenerumab.
IPH 2101 The risk or severity of adverse effects can be increased when IPH 2101 is combined with Gantenerumab.
TB-402 The risk or severity of adverse effects can be increased when TB-402 is combined with Gantenerumab.
Caplacizumab The risk or severity of adverse effects can be increased when Caplacizumab is combined with Gantenerumab.
IMC-1C11 The risk or severity of adverse effects can be increased when IMC-1C11 is combined with Gantenerumab.
Eldelumab The risk or severity of adverse effects can be increased when Eldelumab is combined with Gantenerumab.
Lumiliximab The risk or severity of adverse effects can be increased when Lumiliximab is combined with Gantenerumab.

Target Protein

Amyloid-beta precursor protein APP

Referensi & Sumber

Artikel (PubMed)
  • PMID: 35017413
    Roda AR, Serra-Mir G, Montoliu-Gaya L, Tiessler L, Villegas S: Amyloid-beta peptide and tau protein crosstalk in Alzheimer's disease. Neural Regen Res. 2022 Aug;17(8):1666-1674. doi: 10.4103/1673-5374.332127.
  • PMID: 34110536
    Decourt B, Boumelhem F, Pope ED 3rd, Shi J, Mari Z, Sabbagh MN: Critical Appraisal of Amyloid Lowering Agents in AD. Curr Neurol Neurosci Rep. 2021 Jun 10;21(8):39. doi: 10.1007/s11910-021-01125-y.
  • PMID: 35017410
    Torres AK, Rivera BI, Polanco CM, Jara C, Tapia-Rojas C: Phosphorylated tau as a toxic agent in synaptic mitochondria: implications in aging and Alzheimer's disease. Neural Regen Res. 2022 Aug;17(8):1645-1651. doi: 10.4103/1673-5374.332125.
  • PMID: 21955818
    Bohrmann B, Baumann K, Benz J, Gerber F, Huber W, Knoflach F, Messer J, Oroszlan K, Rauchenberger R, Richter WF, Rothe C, Urban M, Bardroff M, Winter M, Nordstedt C, Loetscher H: Gantenerumab: a novel human anti-Abeta antibody demonstrates sustained cerebral amyloid-beta binding and elicits cell-mediated removal of human amyloid-beta. J Alzheimers Dis. 2012;28(1):49-69. doi: 10.3233/JAD-2011-110977.
  • PMID: 21987394
    Ostrowitzki S, Deptula D, Thurfjell L, Barkhof F, Bohrmann B, Brooks DJ, Klunk WE, Ashford E, Yoo K, Xu ZX, Loetscher H, Santarelli L: Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol. 2012 Feb;69(2):198-207. doi: 10.1001/archneurol.2011.1538. Epub 2011 Oct 10.
  • PMID: 31831056
    Klein G, Delmar P, Voyle N, Rehal S, Hofmann C, Abi-Saab D, Andjelkovic M, Ristic S, Wang G, Bateman R, Kerchner GA, Baudler M, Fontoura P, Doody R: Gantenerumab reduces amyloid-beta plaques in patients with prodromal to moderate Alzheimer's disease: a PET substudy interim analysis. Alzheimers Res Ther. 2019 Dec 12;11(1):101. doi: 10.1186/s13195-019-0559-z.
  • PMID: 33336218
    Klein G, Delmar P, Kerchner GA, Hofmann C, Abi-Saab D, Davis A, Voyle N, Baudler M, Fontoura P, Doody R: Thirty-Six-Month Amyloid Positron Emission Tomography Results Show Continued Reduction in Amyloid Burden with Subcutaneous Gantenerumab. J Prev Alzheimers Dis. 2021;8(1):3-6. doi: 10.14283/jpad.2020.68.
  • PMID: 31883703
    Portron A, Jordan P, Draper K, Muenzer C, Dickerson D, van Iersel T, Hofmann C: A Phase I Study to Assess the Effect of Speed of Injection on Pain, Tolerability, and Pharmacokinetics After High-volume Subcutaneous Administration of Gantenerumab in Healthy Volunteers. Clin Ther. 2020 Jan;42(1):108-120.e1. doi: 10.1016/j.clinthera.2019.11.015. Epub 2019 Dec 26.
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