The protein tyrosine kinase inhibitors imatinib and nilotinib strongly inhibit several mammalian α-carbonic anhydrase isoforms

Seppo Parkkila; Alessio Innocenti; Heini Kallio; Mika Hilvo; Andrea Scozzafava; Claudiu T. Supuran

doi:10.1016/j.bmcl.2009.06.002

The protein tyrosine kinase inhibitors imatinib and nilotinib strongly inhibit several mammalian α-carbonic anhydrase isoforms

Seppo Parkkila, Alessio Innocenti, Heini Kallio, Mika Hilvo, Andrea Scozzafava, Claudiu T. Supuran (Corresponding Author)

BA6308 Health data analytics

Research output: Contribution to journal › Article › Scientific › peer-review

66 Citations (Scopus)

Abstract

The protein tyrosine kinases (PTKs) are essential enzymes in cellular signaling processes that regulate cell growth, differentiation, migration and metabolism. Their inhibition was recently shown to constitute a new modality for treating cancers. Two clinically used PTK inhibitors (PTKIs), imatinib (Glivec™/Gleevec™) and nilotinib (Tasigna™) were investigated for their effects on the zinc enzymes carbonic anhydrases (CAs, EC 4.2.1.1). The two PTKIs inhibited all 13 catalytically active mammalian isoforms CA I–XV with KIs in the range of 4.1 nM–20.2 μM. CA I and CA II were the most potently inhibited isoforms (KIs of 4–32 nM), whereas CA VA and VB showed the lowest affinity for these drugs (KIs of 5.4–20.2 μM). In cancer cells, these inhibitors may interact with CAs in addition to the targets for which they were designed, the PTKs.

Original language	English
Pages (from-to)	4102-4106
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	15
DOIs	https://doi.org/10.1016/j.bmcl.2009.06.002
Publication status	Published - 2009
MoE publication type	A1 Journal article-refereed

Keywords

Imatinib
Nilotinib
Carbonic anhydrase
Isoforms I-XV
Antitumor drug

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bmcl.2009.06.002

Cite this

@article{46b2041c63b84159bba9ea43342e8490,

title = "The protein tyrosine kinase inhibitors imatinib and nilotinib strongly inhibit several mammalian α-carbonic anhydrase isoforms",

abstract = "The protein tyrosine kinases (PTKs) are essential enzymes in cellular signaling processes that regulate cell growth, differentiation, migration and metabolism. Their inhibition was recently shown to constitute a new modality for treating cancers. Two clinically used PTK inhibitors (PTKIs), imatinib (Glivec{\texttrademark}/Gleevec{\texttrademark}) and nilotinib (Tasigna{\texttrademark}) were investigated for their effects on the zinc enzymes carbonic anhydrases (CAs, EC 4.2.1.1). The two PTKIs inhibited all 13 catalytically active mammalian isoforms CA I–XV with KIs in the range of 4.1 nM–20.2 μM. CA I and CA II were the most potently inhibited isoforms (KIs of 4–32 nM), whereas CA VA and VB showed the lowest affinity for these drugs (KIs of 5.4–20.2 μM). In cancer cells, these inhibitors may interact with CAs in addition to the targets for which they were designed, the PTKs.",

keywords = "Imatinib, Nilotinib, Carbonic anhydrase, Isoforms I-XV, Antitumor drug",

author = "Seppo Parkkila and Alessio Innocenti and Heini Kallio and Mika Hilvo and Andrea Scozzafava and Supuran, {Claudiu T.}",

year = "2009",

doi = "10.1016/j.bmcl.2009.06.002",

language = "English",

volume = "19",

pages = "4102--4106",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd.",

number = "15",

}

TY - JOUR

T1 - The protein tyrosine kinase inhibitors imatinib and nilotinib strongly inhibit several mammalian α-carbonic anhydrase isoforms

AU - Parkkila, Seppo

AU - Innocenti, Alessio

AU - Kallio, Heini

AU - Hilvo, Mika

AU - Scozzafava, Andrea

AU - Supuran, Claudiu T.

PY - 2009

Y1 - 2009

N2 - The protein tyrosine kinases (PTKs) are essential enzymes in cellular signaling processes that regulate cell growth, differentiation, migration and metabolism. Their inhibition was recently shown to constitute a new modality for treating cancers. Two clinically used PTK inhibitors (PTKIs), imatinib (Glivec™/Gleevec™) and nilotinib (Tasigna™) were investigated for their effects on the zinc enzymes carbonic anhydrases (CAs, EC 4.2.1.1). The two PTKIs inhibited all 13 catalytically active mammalian isoforms CA I–XV with KIs in the range of 4.1 nM–20.2 μM. CA I and CA II were the most potently inhibited isoforms (KIs of 4–32 nM), whereas CA VA and VB showed the lowest affinity for these drugs (KIs of 5.4–20.2 μM). In cancer cells, these inhibitors may interact with CAs in addition to the targets for which they were designed, the PTKs.

AB - The protein tyrosine kinases (PTKs) are essential enzymes in cellular signaling processes that regulate cell growth, differentiation, migration and metabolism. Their inhibition was recently shown to constitute a new modality for treating cancers. Two clinically used PTK inhibitors (PTKIs), imatinib (Glivec™/Gleevec™) and nilotinib (Tasigna™) were investigated for their effects on the zinc enzymes carbonic anhydrases (CAs, EC 4.2.1.1). The two PTKIs inhibited all 13 catalytically active mammalian isoforms CA I–XV with KIs in the range of 4.1 nM–20.2 μM. CA I and CA II were the most potently inhibited isoforms (KIs of 4–32 nM), whereas CA VA and VB showed the lowest affinity for these drugs (KIs of 5.4–20.2 μM). In cancer cells, these inhibitors may interact with CAs in addition to the targets for which they were designed, the PTKs.

KW - Imatinib

KW - Nilotinib

KW - Carbonic anhydrase

KW - Isoforms I-XV

KW - Antitumor drug

UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-67649946943&partnerID=MN8TOARS

U2 - 10.1016/j.bmcl.2009.06.002

DO - 10.1016/j.bmcl.2009.06.002

M3 - Article

SN - 0960-894X

VL - 19

SP - 4102

EP - 4106

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 15

ER -

The protein tyrosine kinase inhibitors imatinib and nilotinib strongly inhibit several mammalian α-carbonic anhydrase isoforms

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this