Beyond the BET Family: Targeting CBP/p300 with 4-Acyl Pyrroles

Article abstract of DOI:10.1002/anie.201705516

Bromodomain and extra-terminal domain (BET) inhibitors are widely used both as chemical tools to study the biological role of their targets in living organisms and as candidates for drug development against several cancer variants and human disorders. However, non-BET bromodomains such as those in p300 and CBP are less studied. XDM-CBP is a highly potent and selective inhibitor for the bromodomains of CBP and p300 derived from a pan-selective BET BRD-binding fragment. Along with X-ray crystal-structure analysis and thermodynamic profiling, XDM-CBP was used in screenings of several cancer cell lines in vitro to study its inhibitory potential on cancer cell proliferation. XDM-CBP is demonstrated to be a potent and selective CBP/p300 inhibitor that acts on specific cancer cell lines, in particular malignant melanoma, breast cancer, and leukemia.

Full text of DOI:10.1002/anie.201705516

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Accepted Article
Title: Beyond the BET family: targeting CBP/p300 with 4-acyl pyrroles
Authors: Martin Hügle, Xavier Lucas, Dmytro Ostrovskyi, Pierre
Regenass, Stefan Gerhardt, Oliver Einsle, Mirjam Hau,
Manfred Jung, Bernhard Breit, Stefan Günther, and Daniel
Wohlwend
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201705516
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Beyond the BET family: targeting CBP/p300 with 4-acyl pyrroles
Martin Hügle, Xavier Lucas, Dmytro Ostrovskyi, Pierre Regenass, Stefan Gerhardt, Oliver Einsle,
Mirjam Hau, Manfred Jung, Bernhard Breit, Stefan Günther and Daniel Wohlwend*
Abstract: BET bromodomain inhibitors are widely used both as
chemical tools to study the biological role of their targets in living
organisms, and as candidates for drug development against several
cancer variants and human disorders. However, non-BET
bromodomains such as those in p300 and CBP are less studied. Here,
we introduce XDM-CBP, a highly potent and selective inhibitor for the
bromodomains of CBP and p300 derived from a pan-selective BET
BRD-binding fragment. In addition to X-ray crystal structure analysis
and thermodynamic profiling, we used XDM-CBP in in vitro cell
screenings of several cancer cell lines to study its inhibitory potential
on cancer cell proliferation. Our results demonstrate that XDM-CBP
is a potent and selective CBP/p300 inhibitor that acts on specific
cancer cell lines, in particular malignant melanoma, breast cancer,
and leukemia.
chemical probes.[1] Most studies and drug discovery campaigns,
however, focus on six members of the bromodomain and extra-
terminal domain (BET) family. Especially, BRD4 is a proven drug
target for fighting cancer, atherosclerosis, or diabetes.[2] Recently,
great efforts have been made to identify inhibitors for BDs beyond
the BET class.[2] In particular, the BD-containing cAMP response
element-binding protein binding protein (CBP, also CREBBP) was
shown to have a great potential for cancer treatment.[3] CBP and
the close homologue E1A binding protein p300 (p300) co-activate
transcription by bridging specific transcription factors with the
basal transcription machinery.[4] They are also involved in
chromatin relaxation through their histone acetyltransferase
activity.[4] Similarly, they can directly acetylate transcription
factors and thus modulate their activity. Finally, through their
multiple domains, both proteins recruit a variety of proteins of the
tumor immune response that moved them into the focus of
oncology research.[5]
Small molecules inhibiting bromodomains (BDs) represent not
only a novel approach to addressing specific malignancies driven
or controlled by the epigenetic machinery, but also a valuable tool
to study fundamental epigenetic mechanisms by means of
Within recent years four scaffolds could be identified that
inhibit the BDs of CBP and p300 with nanomolar binding affinity
(Supporting Table S1). In 2014, the first nanomolar CBP inhibitor
scaffold was published, showing weak selectivity against
BRD4(1) (KD,CBP = 390 nM, KD,
= 1.4 µM, determined by
BRD4
[a]
Dr. D. Wohlwend
Institut für Biochemie
isothermal titration calorimetry, ITC).[6] The chemical probe SGC-
CBP30 belongs to a second class of CBP inhibitors (KD = 21 nM,
ITC) and is highly selective, although significant affinity was also
observed to BRD4(1) (KD = 850 nM, ITC).[7] This scaffold was
Albert-Ludwigs-Universität Freiburg
Albertstr. 21, D-79104 Freiburg (Germany)
E-mail: wohlwend@bio.chemie.uni-freiburg.de
Prof. Dr. S. Günther
Institut für Pharmazeutische Wissenschaften and Freiburg Institute
for Advanced Studies (FRIAS)
Albert-Ludwigs-Universität Freiburg
Hermann-Herder-Str. 9, D-79104 Freiburg (Germany)
E-mail: stefan.guenther@pharmazie.uni-freiburg.de
M. Hügle,[+] Dr. S. Gerhardt
optimized by Pfizer to give PF-CBP1 (KD
= 190 nM, KD
>
,CBP
,BRD4
20 µM, ITC, >100-fold selectivity). PF-CBP1 downregulates a
number of inflammatory genes in macrophages as well as neuron
specific genes, suggesting a therapeutic opportunity for CBP
inhibitors in the treatment of neurological disorders.[8] I-CBP-112
[b]
belongs to the third CBP-inhibitor class (KD, CBP = 151 nM, KD
,BRD4
Institut für Biochemie
= 5.6 µM, ITC, 40-fold selectivity).[3] It notably reduces the
leukemia-initiating potential of AML cells in vitro and in vivo. Most
recently, Unzue and co-workers[9] presented a molecule with 33-
Albert-Ludwigs-Universität Freiburg
Albertstr. 21, D-79104 Freiburg (Germany)
Dr. X. Lucas[+]
School of Life Sciences, Division of Biological Chemistry and Drug
Discovery
fold selectivity (KD,CBP = 300 nM, ITC, KD
= 9.9 µM, by
,BRD4(1)
competition assay) that acts on leukemia cell lines.
University of Dundee, James Black Centre
Dow Street, Dundee, DD1 5EH (United Kingdom)
Prof. Dr. O. Einsle
Institut für Biochemie, Freiburg Institute for Advanced Studies
(FRIAS) and BIOSS Centre for Biological Signalling Studies
Albert-Ludwigs-Universität Freiburg
Albertstr. 21, D-79104 Freiburg (Germany)
Dr. D. Ostrovskyi,[+] Dr. P. Regenass
Institut für Organische Chemie
Albert-Ludwigs-Universität Freiburg
Albertstr. 21, D-79104 Freiburg (Germany)
Prof. Dr. B. Breit
Institut für Organische Chemie and Freiburg Institute for Advanced
Studies (FRIAS)
In this study we examined the inhibitory potential of fragments
of our recently developed 4-acyl pyrrole based potent BET-
inhibitor XD14[10] on CBP/p300. The core fragment XD46 still
showed substantial affinity towards the BET family[11] but equally
addressed CBP and p300 (Figure 1, Supporting Figure S1).
Consequently, we set out to direct the selectivity of XD46
derivatives away from the BET family toward CBP/p300 using a
combination of computational methods, chemical syntheses, X-
ray crystallography, and ITC.
We initially grew XD46 inside the recognition site of p300 in
silico and identified XDM1 (Figure 1) with a m-chlorobenzyl
attached to the amide anchor of XD46 (Syntheses for all
compounds are given in the Supplementary Information). XDM1
Albert-Ludwigs-Universität Freiburg
Albertstr. 21, D-79104 Freiburg (Germany)
M. Hau, Prof. Dr. M. Jung
Institut für Pharmazeutische Wissenschaften
Albert-Ludwigs-Universität Freiburg
Albertstr. 25, D-79104 Freiburg (Germany)
[+]
These authors contributed equally to this work
Supporting information for this article is given via a link at the end of
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has moderate affinity to both targets, slightly favoring p300 over
CBP (Supporting Figure S2).
Figure 1. Chemical structures of compounds explored during the development of XDM-CBP based on fragment XD46. KD values were determined by ITC.
The crystal structure of XDM1 in complex with CBP (Figure
2A) confirmed that it binds to the recognition pocket of CBP with
five well-conserved water molecules surrounding its 4-acyl pyrrole
core.[12] In addition, the structure presents an induced-fit binding
mode of Pro1110 and Arg1173.[6] As setting up this cavity
depends on binding of a suitable ligand, we designate this motif
the inducible RP cavity. In complex with p300, XDM1 presents a
similar yet more heterogeneous binding, exemplified by three
slightly different binding modes (Supporting Figure S12). Analysis
of the crystal structures of XDM1 with both p300 and CBP using
SiteMap (Schrödinger, LLC, New York, NY, USA) revealed a
hydrophobic region within the ZA channel (Supporting Figure
S13). To address it and at the same time reduce the flexibility of
the chlorobenzyl moiety, we next introduced a 7-chloro-1,2,3,4-
tetrahydronaphthalenyl moiety, thus fixing the m-chlorobenzyl
system (XDM2, Figure 1). The two resulting enantiomers, XDM2a
and XDM2b, were separated by means of chiral HPLC and
characterized by ITC (Supporting Figures S3-4). XDM2a lost
affinity and fell back to the level of the starting fragment XD46.
XDM2b exhibited an apparent 59-fold selectivity toward p300
over CBP, primarily by losing affinity toward the latter (Figure 1).
However, both molecules lacked an adequate solubility due to
their increased hydrophobicity (clogPo/w = 4.99), questioning the
reliability of the affinity determination by ITC and undermining any
attempts of co-crystallization with p300 or CBP. Accordingly, the
absolute configuration of their stereocenters and more reliable
affinities remain unresolved.
XDM3a-d that were separated by means of chiral HPLC. ITC
validation of these compounds showed good binding of p300 to
all of them (Figure 1 and Supporting Figures S5-8). XDM3b and
XDM3c are still recognized by CBP (Supporting Figures S6 and
S7), while XDM3a and XDM3d failed to interact tightly with CBP
(Supporting Figures S5 and S8). Their selectivity toward p300
resembles that of XDM2b, suggesting that the shared absolute
configuration of the carbon atom C1 of XDM3a and XDM3d is
identical to the one of XDM2b. X-ray crystal structures of XDM3c
bound to CBP and XDM3d bound to p300 (Figure 2B, Supporting
Figure S14) allowed for the determination of the absolute
configurations as (R,R) and (S,S), respectively. Both structures
conserve the interaction of the 4-acyl pyrrole moiety with the KAc
binding site. However, in CBP, flipping of the amide linker of
XDM3c induces two slightly different positions of the
tetrahydronaphthyl moiety, whereas in complex with p300, the
amide of XDM3d is fixed in one orientation that forces the tail to
address the ZA channel we initially aimed at. Here, XDM3d
replaces a surface-bound water molecule close to Asp1080 at the
back of the ZA channel, allowing for an interaction of its -system
with the amide head group of Gln1077. However, Arg1137, which
was hypothesized to form an inducible RP cavity with Pro1074,
does not participate in binding. Rather Arg1137 appears to be
constitutively locked in a remote position of the binding pocket by
Tyr1141. Notably, the good discriminatory potential of XDM3d
with respect to CBP and p300 (28-fold selectivity) does not fully
apply to other bromodomains, in particular members of the BET
family (Supporting Figure S9). Moreover, in the crystal structure
we identified two additional binding modes of XDM3d to the
surface of p300 that could not be further resolved by ITC
(Supporting Figures S8 and S15).
Consequently, we added a hydroxyl group at the C2 of the 7-
chloro-1,2,3,4-tetrahydronaphthyl moiety to increase water
solubility, yielding XDM3 (Figure 1, cLogPo/w = 3.96). The second
chiral center gives rise to four stereoisomers, the compounds
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Figure 2. Crystal structures of XDM1 and XDM3c in complex with CBP and of XDM3d bound to p300. (A) XDM1 is recognized by Asn1168 in the KAc binding
site of CBP and stabilized by hydrogen bonds and van der Waals contacts to the hydrophobic pocket core. The 2Fo-Fc omit map at 1.0  is shown for XDM1. (B)
Superposition of the KAc binding sites of CBP bound to XDM3c and p300 bound to XDM3d. XDM3c (yellow sticks) occupies the inducible RP cavity of CBP (yellow
sticks and surface, shown for CBP), while XDM3d (green sticks) binds to the ZA channel of p300 (green side chains and surface, shown for p300). Differing hydrogen
bonds and bridging waters are colored accordingly.
In order to restrict inhibitor binding to the KAc binding site and
to enhance specificity, we focused on improving the surface
complementarity and supporting the -stacking by introducing a
(naphthalene-1-yl)methyl moiety to XDM1, yielding XDM4
(Figure 1). The hydrophobicity of this tail resulted in a weak water
solubility, preventing successful measurements by ITC. However,
we obtained a high-resolution crystal structure of XDM4 in
complex with CBP (Supporting Figure S16). The 4-acyl pyrrole
head exploits the already well-described interactions with CBP.
The amide linker is placed like previously shown for XDM1. As
expected, the extended aromatic tail points towards Arg1173,
thus occupying the inducible RP cavity of CBP.
the additional IMHB by disclosing significantly improved entropy
contributions to binding (Supporting Figure S11A) that resulted in
nanomolar affinities to both proteins and a ligand efficiency (LE)
for CBP of -0.33 kcal/mol. To our knowledge, this is the highest
LE for a nanomolar CBP inhibitor reported to date. In addition,
XDM6 features a good lipophilic LE (LLE) of 3.22 (cLogPo/w
=
3.40), outperformed only by compound 19[9] of Unzue and co-
workers (LLE 3.56, Supporting Table S1). In addition, competition
assays by ITC with the established CBP inhibitor I-CBP-112(3)
show that XDM6 and I-CBP-112 address the same site in the BD
of CBP and that their binding is mutually exclusive (Supporting
Figure S11B-C), demonstrating that the mode of action of XDM6
on the BD of CBP is identical to I-CBP-112.
To increase water solubility and further optimize target affinity
by pursuing an intra-molecular hydrogen bond (IMHB), a hydroxyl
group was introduced to the tail of XDM4, yielding XDM5
(Figure 1). Although attempts to obtain a crystal structure of
XDM5 in complex with either CBP or p300 were not successful,
the affinity to p300 and to CBP was overall substantially improved
compared to XDM3 (Figure 1, Supporting Figure S10).
We next tested the specificity of XDM6 in a bromoKdELECT
screen (DiscoveRx) against 40 BDs (Figure 4A, Supporting
Figure S18). In comparison with the BET-inhibitor XD14,[10] the
specificity of XDM6 is redirected from the BET family towards
CBP/p300, having only little residual affinity to BRD9 (KD = 2.9
M), BRD7 (KD = 4.5 M), BRD2(1), BRPF1 and BRPF3 (all close
to 10 µM), while all other bromodomains, including BRD4(1), are
not recognized under the test conditions (KD > 40 M). The
avoidance of BET BDs can be assigned to the IMHBs in XDM6
that makes a conformational change to adapt to the KAc binding
site of BRD4(1) energetically disfavored (Supporting Figures S17
and S20B). Hence, we name this compound XDM-CBP.
We added a second hydroxyl group to XDM5, producing
XDM6 (Figure 1). This should allow for additional IMHBs to
minimize the rotation of the tail. The co-crystal structures of XDM6
with CBP and p300 reveal poses similar to previously described
XDM4 (Figure 3). The structures confirm the establishment of two
IMHBs between the amide linker and the novel hydroxyl groups
of XDM6 that lock the conformation of the 2,8-
dihydroxynaphthalen-1-yl)methyl moiety (Supporting Figures S16
and S17). This is supported by the low B-factors of this moiety
(average B-factors of 17.8 Å2 for CBP and 18.6 Å2 for p300 with
overall B-factors of 18.5 Å2 and 20.1 Å2, respectively, Supporting
Table S2). A structural comparison with other CBP-inhibitor
complexes reveals that XDM6 is the only inhibitor that is
intrinsically fixed in a conformation that apparently induces a rigid
rotamer fit of Arg1173 (CBP) and Arg1137 (p300, Figure 3B,
Supporting Figure S20A). ITC analysis highlighted the benefits of
Finally, we assessed the antiproliferative activity of XDM-CBP
in the NCI60[13] panel provided by the National Cancer Institute
(NCI, NIH, Rockville, MD, US). While XD14 mainly targeted
leukemia cell lines (Supporting Figures S19 and S27), XDM-CBP
is potent on numerous cancer variants (Figure 4B, Supporting
Figure S26), including leukemia (mean growth inhibition at 10 M
for 48h (GI) of 77%), breast cancer (GI = 74 %), and melanoma
(GI = 73 %). Its potency peaks for individual cell lines of
melanoma (SK-MEL-5), breast cancer (T-47D), and non-small
cell lung cancer (NCI-H522).
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Figure 3. Binding of XDM-CBP to CBP and p300. (A) Recognition of XDM-CBP by CBP is driven by binding of the 4-acyl pyrrole moiety to the KAc binding site
and by the interaction of the naphthalenyl moiety with the inducible RP cavity. (B) Superposition of the KAc binding sites of p300 (green) and CBP (yellow) in
complex with XDM-CBP. The binding mode is largely conserved with only minor differences in the naphthalenyl position.
A detailed analysis of the antiproliferative effect on HL-60 and
MCF-7 cells (Supporting Figure S30) yielded GI50 values of 1.3
µM (HL-60) and 4.2 µM (MCF-7). Here, XDM-CBP proves to be
more efficient than I-CBP-112 in both cell lines, which might by
due to a better LLE of XDM-CBP (LLE of 3.22) as compared to I-
CBP-112 (LLE of 2.68, Supporting Table S1). Interestingly, MCF-
7 cells remain largely unaffected by (+)-JQ1 treatment, a well
characterized BET inhibitor,[14] supporting the discriminatory
potential of XDM-CBP against BET BDs.
Our results demonstrate that XDM-CBP, the final product of
the optimization, is an excellent CBP/p300 inhibitor that combines
outstanding ligand efficiency with high selectivity for CBP/p300
over all other BD families, including the BET family. Most
importantly, XDM-CBP has an antiproliferative effect on
numerous cancer cell lines. This renders XDM-CBP a serious
candidate for further optimization towards initial clinical studies
and it supports the high potential of 4-acyl pyrrole derivatives for
the development of inhibitors and therapeutic agents beyond the
BET BD family.
Figure 4. Specificity and antiproliferative activity of XDM-CBP. (A) Phylogenetic tree of the human BD family with selectivity profiles of XDM-CBP. Sphere
colors indicate the binding affinity to specific BDs, as observed in the BROMOscan assay. (B) Antiproliferative activity of XDM-CBP. Top: Box plot of the sensitivity
of cancer cells covered by the NCI60 panel. Bottom: Top 5 ranked cell lines regarding sensitivity and resistance.
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[6]
[7]
T. P. Rooney, P. Filippakopoulos, O. Fedorov, S. Picaud, W. A.
Cortopassi, D. A. Hay, S. Martin, A. Tumber, C. M. Rogers, M. Philpott,
M. Wang, A. L. Thompson, T. D. Heightman, D. C. Pryde, A. Cook, R. S.
Paton, S. Muller, S. Knapp, P. E. Brennan, S. J. Conway, Angew. Chem.
Int. Ed. Engl. 2014, 53, 6126-30.
Acknowledgements
This work was financially supported by the DFG (GU1225/3-1, X.
L., and WO2012/1-1, M. H.). S. G., D. O., B. B., M. J., and O. E.
received funding from the DFG (CRC 992 ‘Medical Epigenetics’).
The authors thank the staff of the Swiss Light Source (SLS)
beamlines X06SA and X06DA for excellent technical support.
D. A. Hay, O. Fedorov, S. Martin, D. C. Singleton, C. Tallant, C. Wells,
S. Picaud, M. Philpott, O. P. Monteiro, C. M. Rogers, S. J. Conway, T. P.
Rooney, A. Tumber, C. Yapp, P. Filippakopoulos, M. E. Bunnage, S.
Muller, S. Knapp, C. J. Schofield, P. E. Brennan, J. Am. Chem. Soc. 2014,
136, 9308-19.
[8]
[9]
E. L. Chekler, J. A. Pellegrino, T. A. Lanz, R. A. Denny, A. C. Flick, J.
Coe, J. Langille, A. Basak, S. Liu, I. A. Stock, P. Sahasrabudhe, P. D.
Bonin, K. Lee, M. T. Pletcher, L. H. Jones, Chem. Biol. 2015, 22, 1588-
96.
Keywords: bromodomains • CBP • p300 • drug discovery • 4-
acyl pyrroles
A. Unzue, M. Xu, J. Dong, L. Wiedmer, D. Spiliotopoulos, A. Caflisch, C.
Nevado, J. Med. Chem. 2016, 59, 1350-6.
[1]
[2]
[3]
T. Fujisawa, P. Filippakopoulos, Nat. Rev. Mol. Cell Biol. 2017, 18, 246-
62.
[10] X. Lucas, D. Wohlwend, M. Hügle, K. Schmidtkunz, S. Gerhardt, R.
Schüle, M. Jung, O. Einsle, S. Günther, Angew. Chem. Int. Ed. Engl.
2013, 52, 14055-9.
N. H. Theodoulou, N. C. Tomkinson, R. K. Prinja, P. G. Humphreys, Curr.
Opin. Chem. Biol. 2016, 33, 58-66.
S. Picaud, O. Fedorov, A. Thanasopoulou, K. Leonards, K. Jones, J.
Meier, H. Olzscha, O. Monteiro, S. Martin, M. Philpott, A. Tumber, P.
Filippakopoulos, C. Yapp, C. Wells, K. H. Che, A. Bannister, S. Robson,
U. Kumar, N. Parr, K. Lee, D. Lugo, P. Jeffrey, S. Taylor, M. L. Vecellio,
C. Bountra, P. E. Brennan, A. O'Mahony, S. Velichko, S. Müller, D. Hay,
D. L. Daniels, M. Urh, N. B. La Thangue, T. Kouzarides, R. Prinjha, J.
Schwaller, S. Knapp, Cancer Res. 2015, 75, 5106-19.
[11] M. Hügle, X. Lucas, G. Weitzel, D. Ostrovskyi, B. Breit, S. Gerhardt, O.
Einsle, S. Günther, D. Wohlwend, J. Med. Chem. 2016, 59, 1518-30.
[12] M. Xu, A. Unzue, J. Dong, D. Spiliotopoulos, C. Nevado, A. Caflisch, J.
Med. Chem. 2016, 59, 1340-9.
[13] R. H. Shoemaker, Nat. Rev. Cancer 2006, 6, 813-23.
[14] P. Filippakopoulos, J. Qi, S. Picaud, Y. Shen, W. B. Smith, O. Fedorov,
E. M. Morse, T. Keates, T. T. Hickman, I. Felletar, M. Philpott, S. Munro,
M. R. McKeown, Y. Wang, A. L. Christie, N. West, M. J. Cameron, B.
Schwartz, T. D. Heightman, N. La Thangue, C. A. French, O. Wiest, A.
L. Kung, S. Knapp, J. E. Bradner, Nature 2010, 468, 1067-73.
[4]
[5]
N. Shiama, Trends Cell Biol. 1997, 7, 230-6.
F. A. Romero, A. M. Taylor, T. D. Crawford, V. Tsui, A. Cꢀtꢁ, S.
Magnuson, J. Med. Chem. 2016, 59, 1271-98.
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COMMUNICATION
XDM-CBP is a selective, potent and
cell active CBP/p300 inhibitor
Martin Hügle, Xavier Lucas, Dmytro
Ostrovskyi, Pierre Regenass, Stefan
Gerhardt, Oliver Einsle, Bernhard Breit,
Stefan Günther and Daniel Wohlwend*
Page No. – Page No.
Beyond the BET family: targeting
CBP/p300 with 4-acyl pyrroles
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