Targeting Glial Cells by Organic Anion-Transporting Polypeptide
1C1 (OATP1C1)-Utilizing <sc>l</sc>-Thyroxine-Derived Prodrugs

J 2023

Targeting Glial Cells by Organic Anion-Transporting Polypeptide 1C1 (OATP1C1)-Utilizing <sc>l</sc>-Thyroxine-Derived Prodrugs

TONDURU, Arun Kumar; Seyed Hamed MALJAEI; Santosh Kumar ADLA; Landry ANAMEA; Janne TAMPIO et. al.

Základní údaje

Originální název

Targeting Glial Cells by Organic Anion-Transporting Polypeptide 1C1 (OATP1C1)-Utilizing <sc>l</sc>-Thyroxine-Derived Prodrugs

Autoři

Vydání

Journal of Medicinal Chemistry, Washington, American Chemical Society, 2023, 0022-2623

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30400 3.4 Medical biotechnology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.900

Kód RIV

RIV/00216224:90127/23:00139046

Organizační jednotka

CIISB II

DOI

http://dx.doi.org/10.1021/acs.jmedchem.3c01026

UT WoS

001142966000001

EID Scopus

2-s2.0-85178194269

Klíčová slova anglicky

BRAIN DELIVERY; IDENTIFICATION; EXPRESSION; RESIDUES; PHARMACOKINETICS; SUPERFAMILY; INHIBITOR; RELEVANCE; ACCURACY; DYNAMICS

Štítky

CF PROT, ne MU, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 13. 3. 2025 09:56, Mgr. Eva Dubská

Anotace

V originále

OATP1C1 (organic anion-transporting polypeptide 1C1) transports thyroid hormones, particularly thyroxine (T4), into human astrocytes. In this study, we investigated the potential of utilizing OATP1C1 to improve the delivery of anti-inflammatory drugs into glial cells. We designed and synthesized eight novel prodrugs by incorporating T-4 and 3,5-diiodo-l-tyrosine (DIT) as promoieties to selected anti-inflammatory drugs. The prodrug uptake in OATP1C1-expressing human U-87MG glioma cells demonstrated higher accumulation with T-4 promoiety compared to those with DIT promoiety or the parent drugs themselves. In silico models of OATP1C1 suggested dynamic binding for the prodrugs, wherein the pose changed from vertical to horizontal. The predicted binding energies correlated with the transport profiles, with T-4 derivatives exhibiting higher binding energies when compared to prodrugs with a DIT promoiety. Interestingly, the prodrugs also showed utilization of oatp1a4/1a5/1a6 in mouse primary astrocytes, which was further supported by docking studies and a great potential for improved brain drug delivery.

Návaznosti

90127, velká výzkumná infrastruktura

Název: CIISB II

Citovat

TONDURU, Arun Kumar; Seyed Hamed MALJAEI; Santosh Kumar ADLA; Landry ANAMEA; Janne TAMPIO; Adela KRALOVA; Aaro J JALKANEN; Catarina ESPADA; Ines Falcato SANTOS; Ahmed B MONTASER; Jarkko RAUTIO; Thales KRONENBERGER; Antti POSO a Kristiina M HUTTUNEN. Targeting Glial Cells by Organic Anion-Transporting Polypeptide 1C1 (OATP1C1)-Utilizing <sc>l</sc>-Thyroxine-Derived Prodrugs. Journal of Medicinal Chemistry. Washington: American Chemical Society, 2023, roč. 66, č. 22, s. 15094-15114. ISSN 0022-2623. Dostupné z: https://dx.doi.org/10.1021/acs.jmedchem.3c01026.

@article{2483609,
   author = {Tonduru, Arun Kumar and Maljaei, Seyed Hamed and Adla, Santosh Kumar and Anamea, Landry and Tampio, Janne and Kralova, Adela and Jalkanen, Aaro J and Espada, Catarina and Santos, Ines Falcato and Montaser, Ahmed B and Rautio, Jarkko and Kronenberger, Thales and Poso, Antti and Huttunen, Kristiina M},
   article_location = {Washington},
   article_number = {22},
   doi = {http://dx.doi.org/10.1021/acs.jmedchem.3c01026},
   keywords = {BRAIN DELIVERY; IDENTIFICATION; EXPRESSION; RESIDUES; PHARMACOKINETICS; SUPERFAMILY; INHIBITOR; RELEVANCE; ACCURACY; DYNAMICS},
   language = {eng},
   issn = {0022-2623},
   journal = {Journal of Medicinal Chemistry},
   title = {Targeting Glial Cells by Organic Anion-Transporting Polypeptide 1C1 (OATP1C1)-Utilizing <sc>l</sc>-Thyroxine-Derived Prodrugs},
   url = {https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c01026},
   volume = {66},
   year = {2023}
}

TY  - JOUR
ID  - 2483609
AU  - Tonduru, Arun Kumar - Maljaei, Seyed Hamed - Adla, Santosh Kumar - Anamea, Landry - Tampio, Janne - Kralova, Adela - Jalkanen, Aaro J - Espada, Catarina - Santos, Ines Falcato - Montaser, Ahmed B - Rautio, Jarkko - Kronenberger, Thales - Poso, Antti - Huttunen, Kristiina M
PY  - 2023
TI  - Targeting Glial Cells by Organic Anion-Transporting Polypeptide 1C1 (OATP1C1)-Utilizing <sc>l</sc>-Thyroxine-Derived Prodrugs
JF  - Journal of Medicinal Chemistry
VL  - 66
IS  - 22
SP  - 15094-15114
EP  - 15094-15114
PB  - American Chemical Society
SN  - 00222623
KW  - BRAIN DELIVERY
KW  - IDENTIFICATION
KW  - EXPRESSION
KW  - RESIDUES
KW  - PHARMACOKINETICS
KW  - SUPERFAMILY
KW  - INHIBITOR
KW  - RELEVANCE
KW  - ACCURACY
KW  - DYNAMICS
UR  - https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c01026
N2  - OATP1C1 (organic anion-transporting polypeptide 1C1) transports thyroid hormones, particularly thyroxine (T4), into human astrocytes. In this study, we investigated the potential of utilizing OATP1C1 to improve the delivery of anti-inflammatory drugs into glial cells. We designed and synthesized eight novel prodrugs by incorporating T-4 and 3,5-diiodo-l-tyrosine (DIT) as promoieties to selected anti-inflammatory drugs. The prodrug uptake in OATP1C1-expressing human U-87MG glioma cells demonstrated higher accumulation with T-4 promoiety compared to those with DIT promoiety or the parent drugs themselves. In silico models of OATP1C1 suggested dynamic binding for the prodrugs, wherein the pose changed from vertical to horizontal. The predicted binding energies correlated with the transport profiles, with T-4 derivatives exhibiting higher binding energies when compared to prodrugs with a DIT promoiety. Interestingly, the prodrugs also showed utilization of oatp1a4/1a5/1a6 in mouse primary astrocytes, which was further supported by docking studies and a great potential for improved brain drug delivery.
ER  -

TONDURU, Arun Kumar; Seyed Hamed MALJAEI; Santosh Kumar ADLA; Landry ANAMEA; Janne TAMPIO; Adela KRALOVA; Aaro J JALKANEN; Catarina ESPADA; Ines Falcato SANTOS; Ahmed B MONTASER; Jarkko RAUTIO; Thales KRONENBERGER; Antti POSO a Kristiina M HUTTUNEN. Targeting Glial Cells by Organic Anion-Transporting Polypeptide 1C1 (OATP1C1)-Utilizing \&{}lt;sc\&{}gt;l\&{}lt;/sc\&{}gt;-Thyroxine-Derived Prodrugs. \textit{Journal of Medicinal Chemistry}. Washington: American Chemical Society, 2023, roč.~66, č.~22, s.~15094-15114. ISSN~0022-2623. Dostupné z: https://dx.doi.org/10.1021/acs.jmedchem.3c01026.

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