ACS Medicinal Chemistry Letters
Page 6 of 12
Author Contributions
(10) Cheng, J. D.; Valianou, M.; Canutescu, A. A.; Jaffe, E. K.; Lee,
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H.-O.; Wang, H.; Lai, J. H.; Bachovchin, W. W.; Weiner, L. M.
Abrogation of Fibroblast Activation Protein Enzymatic Activity
Attenuates Tumor Growth. Mol. Cancer Ther. 2005, 4 (3), 351–360.
The manuscript was written through contributions of all authors. /
All authors have given approval to the final version of the manu-
⊥
script. / These authors contributed equally.
(
11) Lee, H.-O.; Mullins, S. R.; Franco-Barraza, J.; Valianou, M.;
Cukierman, E.; Cheng, J. D. FAP-Overexpressing Fibroblasts Produce
an Extracellular Matrix That Enhances Invasive Velocity and
Directionality of Pancreatic Cancer Cells. BMC Cancer 2011, 11 (1),
245.
Funding Sources
This work received support from a GOA-BOF 2015 grant
of the University of Antwerp (30729) and a research grant
from the Science Foundation Flanders (FWO-Vlaanderen,
grant number G038515N).
(
12) Bainbridge, T. W.; Dunshee, D. R.; Kljavin, N. M.; Skelton, N.
J.; Sonoda, J.; Ernst, J. A. Selective Homogeneous Assay for
Circulating Endopeptidase Fibroblast Activation Protein (FAP). Sci.
Rep. 2017, 7 (1), 12524. doi: 10.1038/s41598-017-12900-8.
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ACKNOWLEDGMENT
(
13) Jansen, K.; Heirbaut, L.; Cheng, J. D.; Joossens, J.; Ryabtsova,
An De Decker, Dries van Rompaey and Anke Peeraer are
grateful to the Fund for Scientific Research-Vlaanderen
O.; Cos, P.; Maes, L.; Lambeir, A.-M.; De Meester, I.; Augustyns, K.;
Van der Veken, P.; Selective Inhibitors of Fibroblast Activation Protein
(
FAP) with a (4-Quinolinoyl)-Glycyl-2-Cyanopyrrolidine Scaffold.
ACS Med. Chem. Lett. 2013, 4 (5), 491–496.
14) Li, J.; Chen, K.; Liu, H.; Cheng, K.; Yang, M.; Zhang, J.;
(
FWO-Vlaanderen) for a PhD scholarship.
(
ABBREVIATIONS
Cheng, J. D.; Zhang, Y.; Cheng, Z. Activatable Near-Infrared
Fluorescent Probe for In Vivo Imaging of Fibroblast Activation Protein-
Alpha. Bioconjug. Chem. 2012, 23 (8), 1704–1711.
(15) Loktev, A.; Lindner, T.; Mier, W.; Debus, J.; Altmann, A.;
Jäger, D.; Giesel, F.; Kratochwil, C.; Barthe, P.; Roumestand, C.;
ABP, Activity-Based Probe; DCM, dichloromethane;
DIPEA, di-isopropylethylamine; DPP, dipeptidyl peptidase;
FAP, fibroblast activation protein; MRM, multiple reaction
monitoring; PREP, prolyl oligopeptidase; SI, selectivity in-
dex; TEA, triethylamine; T3P, 1-propanephosphonic anhy-
dride.
Haberkorn, U.
Associated Fibroblasts. J. Nucl. Med. 2018, 59 (9), 1423–1429.
16) Lindner, T.; Loktev, A.; Altmann, A.; Giesel, F.; Kratochwil,
A Tumor-Imaging Method Targeting Cancer-
(
C.; Debus, J.; Jäger, D.; Mier, W.; Haberkorn, U. Development of
Quinoline-Based Theranostic Ligands for the Targeting of Fibroblast
Activation Protein. J. Nucl. Med. 2018, 59 (9), 1415–1422.
REFERENCES
(1) Park, J. E.; Lenter, M. C.; Zimmermann, R. N.; Garin-Chesa, P.;
Old, L. J.; Rettig, W. J. Fibroblast Activation Protein, a Dual
Specificity Serine Protease Expressed in Reactive Human Tumor
Stromal Fibroblasts. J. Biol. Chem. 1999, 274 (51), 36505–36512.
(
17) Giesel, F.; Kratochwil, C.; Lindner, T.; Marschalek, M.;
Loktev, A.; Lehnert, W.; Debus, J.; Jäger, D.; Flechsig, P.; Altmann,
A.; Mier, W.; Haberkorn, U. FAPI-PET/CT: Biodistribution and
Preliminary Dosimetry Estimate of Two DOTA-Containing FAP-
Targeting Agents in Patients with Various Cancers. J. Nucl. Med. 2018,
https://doi.org/10.2967/jnumed.118.215913.
(
2) Hamson, E. J.; Keane, F. M.; Tholen, S.; Schilling, O.; Gorrell,
M. D. Understanding Fibroblast Activation Protein (FAP): Substrates,
Activities, Expression and Targeting for Cancer Therapy.
PROTEOMICS - Clin. Appl. 2014, 8 (5–6), 454–463.
(
18) Jansen, K.; Heirbaut, L.; Verkerk, R.; Cheng, J. D.; Joossens,
J.; Cos, P.; Maes, L.; Lambeir, A.-M.; De Meester, I.; Augustyns, K.;
Van der Veken, P. Extended Structure–Activity Relationship and
(
3) Edosada, C. Y.; Quan, C.; Tran, T.; Pham, V.; Wiesmann, C.;
Fairbrother, W.; Wolf, B. B. Peptide Substrate Profiling Defines
Fibroblast Activation Protein as an Endopeptidase of Strict Gly -Pro
-Cleaving Specificity. FEBS Lett. 2006, 580 (6), 1581–1586.
4) Fan, M.-H.; Zhu, Q.; Li, H.-H.; Ra, H.-J.; Majumdar, S.; Gulick,
Pharmacokinetic
Investigation
of
(4-Quinolinoyl)Glycyl-2-
2
Cyanopyrrolidine Inhibitors of Fibroblast Activation Protein (FAP). J.
Med. Chem. 2014, 57 (7), 3053–3074.
1
(
(
19) Poplawski, S. E.; Lai, J. H.; Li, Y.; Jin, Z.; Liu, Y.; Wu, W.;
D. L.; Jerome, J. A.; Madsen, D. H.; Christofidou-Solomidou, M.;
Speicher, D. W.; Bachovchin, W.W.; Feghali, Bostwick, C.; Puré, E.
Fibroblast Activation Protein (FAP) Accelerates Collagen Degradation
and Clearance from Lungs in Mice. J. Biol. Chem. 2016, 291 (15),
Wu, Y.; Zhou, Y.; Sudmeier, J. L.; Sanford, D. G.; Bachovchin, W.W.
Identification of Selective and Potent Inhibitors of Fibroblast
Activation Protein and Prolyl Oligopeptidase. J. Med. Chem. 2013, 56
(
9), 3467–3477.
20) Keane, F. M.; Yao, T.-W.; Seelk, S.; Gall, M. G.; Chowdhury,
8
070–8089.
5) Lay, A. J.; Zhang, H. E.; McCaughan, G. W.; Gorrell, M. D.
Fibroblast Activation Protein in Liver Fibrosis. Front. Biosci.. 2019,
(
(
S.; Poplawski, S. E.; Lai, J. H.; Li, Y.; Wu, W.; Farrell, P.; Vieira de
Ribeiro, A.J.; Osborne, B.; Yu, D.M.; Seth, D.; Rahman, K.; Haber, P.;
Topaloglu, A.K.; Wang, C.; Thomson, S.; Hennessy, A.; Prins, J.;
Twigg, S.M.; McLennan, S.V.; McCaughan, G.W.; Bachovchin,
W.W.; Gorrell, M.D. Quantitation of Fibroblast Activation Protein
2
4, 1–17.
(6) Van der Geest, T.; Roeleveld, D. M.; Walgreen, B.; Helsen, M.
M.; Nayak, T. K.; Klein, C.; Hegen, M.; Storm, G.; Metselaar, J. M.;
van den Berg, W. B.; van der Kraan, P.M.; Laverman, P.; Boerman,
O.C.; Koenders, M.I. Imaging Fibroblast Activation Protein to Monitor
Therapeutic Effects of Neutralizing Interleukin-22 in Collagen-
Induced Arthritis. Rheumatology 2018, 57 (4), 737–747.
(7) Brokopp, C. E.; Schoenauer, R.; Richards, P.; Bauer, S.;
Lohmann, C.; Emmert, M. Y.; Weber, B.; Winnik, S.; Aikawa, E.;
Graves, K.; Genoni, M.; Vocht, P.; Lüscher, T.F.; Renner, C.;
Hoerstrup, S.P.; Matter, C.M. Fibroblast Activation Protein Is Induced
by Inflammation and Degrades Type I Collagen in Thin-Cap
Fibroatheromata. Eur. Heart J. 2011, 32 (21), 2713–2722.
(
FAP)-Specific Protease Activity in Mouse, Baboon and Human Fluids
and Organs. FEBS Open Bio 2014, 4 (1), 43–54.
(21) Dvořáková, P.; Bušek, P.; Knedlík, T.; Schimer, J.; Etrych, T.;
Kostka, L.; Stollinová Šromová, L.; Šubr, V.; Šácha, P.; Šedo, A.;
Konvalinka, J. Inhibitor-Decorated Polymer Conjugates Targeting
Fibroblast Activation Protein. J. Med. Chem. 2017, 60 (20), 8385–
8
393.
(22) Gladysz, R.; Lambeir, A.-M.; Joossens, J.; Augustyns, K.; Van
der Veken, P. Substrate Activity Screening (SAS) and Related
Approaches in Medicinal Chemistry. ChemMedChem 2016, 11 (5),
(8) Puré, E.; Blomberg, R. Pro-Tumorigenic Roles of Fibroblast
Activation Protein in Cancer: Back to the Basics. Oncogene 2018, 37
4
67–476.
23) Schade, J.; Stephan, M.; Schmiedl, A.; Wagner, L.; Niestroj, A.
(
(
32), 4343–4357.
9) Yazbeck, R.; Jaenisch, S. E.; Abbott, C. A. Potential Disease
J.; Demuth, H.-U.; Frerker, N.; Klemann, C.; Raber, K. A.; Pabst, R.;
Von Hörsten, S. Regulation of Expression and Function of Dipeptidyl
Peptidase 4 (DP4), DP8/9, and DP10 in Allergic Responses of the Lung
in Rats. J. Histochem. Cytochem. 2008, 56 (2), 147–155.
(
Biomarkers: Dipeptidyl Peptidase 4 and Fibroblast Activation Protein.
Protoplasma 2018, 255 (1), 375–386.
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