Novel series of pyrrolotriazine analogs as highly potent pan-Aurora kinase inhibitors

Article abstract of DOI:10.1016/j.bmcl.2011.07.027

The synthesis and SAR for a novel series of pyrrolotriazines as pan-Aurora kinase inhibitors are described. Optimization of the cyclopropane carboxamide terminus of lead compound 1 resulted in analogs with high cellular activity and improved rat PK profiles. Notably, compound 17l demonstrated tumor growth inhibition in a mouse xenograft model.

Full text of DOI:10.1016/j.bmcl.2011.07.027

Bioorganic & Medicinal Chemistry Letters 21 (2011) 5296–5300
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Novel series of pyrrolotriazine analogs as highly potent pan-Aurora
kinase inhibitors
Sunny Abraham a, Michael J. Hadd a, Lan Tran a, Troy Vickers a, Janice Sindac a, Zdravko V. Milanov a,
Mark W. Holladay a, Shripad S. Bhagwat a, Helen Hua b, Julia M. Ford Pulido b, Merryl D. Cramer c,
Dana Gitnick c, Joyce James c, Alan Dao b, Barbara Belli b, Robert C. Armstrong b, Daniel K. Treiber d,
Gang Liu a,
⇑
a Department of Medicinal Chemistry, Ambit Biosciences Corporation, 4215 Sorrento Valley Boulevard, San Diego, CA 92121, United States
b Department of Cell Biology and Pharmacology, Ambit Biosciences Corporation, 4215 Sorrento Valley Boulevard, San Diego, CA 92121, United States
c Department of DMPK, Ambit Biosciences Corporation, 4215 Sorrento Valley Boulevard, San Diego, CA 92121, United States
d Department of Technology Development, Ambit Biosciences Corporation, 4215 Sorrento Valley Boulevard, San Diego, CA 92121, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis and SAR for a novel series of pyrrolotriazines as pan-Aurora kinase inhibitors are described.
Optimization of the cyclopropane carboxamide terminus of lead compound 1 resulted in analogs with
high cellular activity and improved rat PK profiles. Notably, compound 17l demonstrated tumor growth
inhibition in a mouse xenograft model.
Received 1 June 2011
Revised 28 June 2011
Accepted 6 July 2011
Available online 14 July 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Aurora kinase
Serine/threonine kinase
Specificity
Tumor xenograft model
Aurora kinases (Aurora A, B, C), a family of serine/threonine
kinases, play a key role in regulating cell mitosis. Aurora A, ubiqui-
tously expressed, regulates mitotic entry and centrosome matura-
tion.1 Aurora B, also widely distributed, is essential for chromatin
remodeling and cytokinesis. It is also known to phosphorylate his-
tone H3 (HH3) at Ser-10 during mitosis.2 Aurora C’s function dur-
ing mitosis is much less well defined, and it is suggested to have an
overlapping role with Aurora B.3 Accordingly, inhibition of Aurora
kinases results in cell cycle disruption and cell death. Both Aurora
A and B gene amplification and protein over-expression have been
frequently detected in a variety of tumors. Thus, disruption of
overly active Aurora function is expected to impair tumor growth
and has the potential for broad antitumor activity in a number of
cancers.4
relation to the Aurora isoform selectivity has not yet been defined
clinically.
Compound 1 ( Fig. 1), a novel lead molecule based on the
N-(1H-pyrazol-3-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine scaffold, was
disclosed as an ATP-competitive, pan-Aurora inhibitor, with moder-
ate activity in inhibiting pHH3 formation and proliferation in HCT-
116 cells.9 Herein we report the structure–activity relationship
NH
N
HN
Kds = 4, 7, 6 nM (Aurora A, B, C)
IC50 = 55 nM (HCT-116 pHH3)
IC50 = 28 nM (HCT-116 proliferation)
H
N
N
O
N
N
S
N
Based on these premises, the Aurora kinases have been actively
pursued as targets for the discovery of new cancer chemotherapeu-
tics.5 As a result, several small molecule inhibitors of Aurora
kinases have been identified, some of which have reached clinical
evaluation, including Aurora-A selective MLN8054,6 Aurora-B
selective AZD11527 and pan-Aurora inhibitor VX-680 (MK-0457)8
(Fig. 1). However, the ideal inhibitor profile for therapeutic use in
VX-680 (MK-0457)
NH
N
HN
Kds = 12, 20, 4 nM (Aurora A, B, C)
IC50 = 431 nM (HCT-116 pHH3)
IC50 = 345 nM (HCT-116 proliferation)
H
N
N
N
O
N
S
1
⇑
Figure 1. Literature pan-Aurora inhibitor and internal lead compound (Ambit
internal data).
Corresponding author. Tel.: +1 858 334 2164; fax: +1 858 334 2192.
E-mail address: gliu@ambitbio.com (G. Liu).
0960-894X/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2011.07.027

S. Abraham et al. / Bioorg. Med. Chem. Lett. 21 (2011) 5296–5300
5297
O2N
amino compound 8. Subsequent elaboration of the amino group as
shown in Scheme 1 yielded analogs 9a–9e.
As shown in Table 1, among the aminoalkyl amides prepared
(9a–9d), only the morpholino- (9b) and D-prolinol- (9d) analogs
Cl
O
NH2
a
c
b
NH
O
N
N
O2N
O2N
N
O
N
NH2
N
Cl
N
H
3
2
4
achieved similar binding affinity11 to compound 1, while piperidi-
nyl analog 9a and morpholino analog 9b exhibited slightly im-
proved cell activity in inhibiting HCT-116 cell proliferation. The
urea analog 9e was found to have equivalent binding affinity for
Aurora kinases, and two to fourfold improvement in cellular activ-
ity. However, 9e suffered high clearance in a screening rat PK
study, compared to 1 (Table 5).
The compounds described herein were also monitored for their
kinase selectivity in a panel of 317 kinases (290 distinct kinases
plus the mutants) using the KinomeScan technology. In most cases,
the kinome selectivity dropped off with the introduction of basic
amines, reflected by the increase in selectivity score12 compared
to lead compound 1 (S10 score of 0.03 vs a panel of 202 distinct
kinases). Such shift of kinome selectivity usually implies additional
interactions with non-Aurora kinases elicited by the additional
6-position substituents.
SAR attention was then turned to the modification of the cyclo-
propane carboxamide portion of the molecule via functionalizing
the amide terminus. X-ray structure of 1 in complex with Aurora
A suggests that the cyclopropane carboxamide points to the back
specificity pocket (data not shown). Hydrophilic (basic) groups
have been successfully introduced in this region of the protein in
kinase inhibitor design, exemplified by the successful discovery
of imatinib.13 Synthesis of these compounds was made possible
by acylation of compound 109 with either chloroacetyl chloride
or bromoacetic anhydride, followed by straightforward displace-
ment of the halides with various amines to give 12a–12e (Scheme
2).
NH
NH
N
N
N
HN
H
N
HN
e
d
N
O2N
O2N
N
O
N
N
S
N
Cl
5
7
NH
N
N
f
9a
HN
H
N
g, h
i, j
9b 9d
-
H2N
N
N
O
S
9e
8
Scheme 1. Reagents and conditions: (a) ethyl chloroformate, pyridine, dioxane,
125 °C, 72%; (b) POCl3, TEA, reflux, 125 °C, 37%; (c) 5-methyl-1H-pyrazol-3-amine,
KI, DIEA, DMF, rt, 46%; (d) N-(4-mercaptophenyl)cyclopropanecarboxamide (6),
K2CO3, DMF, 120 °C, 12 h, 39%; (e) Raney Ni, H2, MeOH; (f) EDC, HOBT, DIEA, DMF,
rt, 3-(piperidin-1-yl)propanoic acid, 54% over two steps; (g) (BrCH2CO)2O, THF, 83%
over two steps; (h) amines, rt, ca. 67%; (i) 4-nitrophenyl carbonochloridate, THF; (j)
1-methylpiperazine, TEA, THF, 8% over three steps.
(SAR) development of this series of compounds aimed at producing
highly potent analogs with desirable PK profiles by using various ba-
sic groups as formal solubilizing groups in different regions of the
molecule. Sucha strategyhas been widely applied in kinase inhibitor
design to improve the cellular activity and solubility of resulting
inhibitors. It is also compatible with parenteral administration,
which is desired for minimizing any potential gastrointestinal toxic-
ity associated with orally dosed pan-Aurora inhibitors.
SAR studies began with modifications at the 6-position of pyr-
rolotriazine, due to synthetic accessibility and a favorable vector
for reaching a solvent exposed space from this position. Synthesis
of such compounds started from the nitro amino pyrrole 2,10 which
was converted to the dione 3 (Scheme 1). Chlorination of 3 using
POCl3 followed by regioselective displacement of the 4-chloro
group in 4 with aminopyrrazole afforded compound 5. Nucleo-
philic substitution of the 2-chloro in 5 with benzenethiol 6 pro-
vided the amide 7. The nitro group of 7 was reduced using Raney
nickel without affecting the sulfide bond to give a somewhat labile
SAR for some representative aminoacetamides is shown in
Table 2. No boost in the potency was observed with most of ana-
logs (12a–12d), regardless of the amines attached at the
of the acetamide. Compound 12e, an acetamide with (S)-pyrroli-
din-2-ylmethanol at the -position, exhibited marginally im-
a-position
a
proved cell potency and moderate kinome selectivity. The
presence of an alcohol group in 12e should in principle be favor-
able in solubilizing the compound and in providing a handle for
further functionalization. Compound 12e did suggest that the
Table 1
SAR of substitution on 6-amino pyrrolotriazines for Aurora kinases
NH
N
N
HN
H
N
HN
O
N
O
R
N
S
9a-9e
a
a
Entry
R
Aurora Kd (nM)
Cell IC50 (nM)
Proliferation (HCT-116)
Kinase specificity score S(10)
0.27
A
B
C
pHH3 (HCT-116)
850
N
9a
38
37
10
101
N
O
9b
9c
7
9
3
420
828
160
536
0.12
0.08
N
23
49
13
N
9d
9e
10
7
16
4
80
5
6300
190
536
75
0.34
0.31
HO
O
N
N
a
Each experiment was run in duplicate and the values shown are the average of the two.

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S. Abraham et al. / Bioorg. Med. Chem. Lett. 21 (2011) 5296–5300
NH
NH
NH
N
NH
OH
N
N
N
N
N
N
O
OTr
a
b
ClH2N
OH
HN
HN
HN
HN
H
N
H
N
O
H
N
Boc
NH2
Boc
Cl(Br)
N
NR1R2
N
N
f
a,b,c
d,e
N
O
N
N
N
O
N
O
N
N
O
N
S
S
N
S
S
O
O
OH
13
O2S
10
11
12a-12e
F
14
15
16
F
Scheme 2. Reagents and conditions: (a) chloroacetyl chloride, THF, 0 °C–rt, 97%; or
bromoacetic anhydride, THF, À15 °C to rt, 76%; (b) HNR1R2, KI, DIEA, DMF, 70 °C,
10–44%.
Scheme 3. Reagents and conditions: (a) LiBH4, THF, 80 °C, 5 h, (b) Tr-Cl, Pyr. rt, 4 d,
61% over two steps; (c) MsCl, TEA, DCM, rt, 99%; (d) p-fluorophenol, DMF,
microwave, 30 min, 120 °C, 77%; (e) 4 N HCl in Dioxane, rt; (f) 11, KI, DIEA, DMF,
70 °C, 3 h, 33%.
a-aminoacetamide side chain could be a productive area for fur-
ther SAR exploration.
Encouraged by the results of 12e, the effect of additional substi-
tution at the 4-position of the pyrrolidine ring was examined.
Scheme 3 describes one representative example of requisite analog
preparation. Hydroxyproline carboxylate 13 was reduced and the
resulting primary alcohol was selectively capped as its trityl ether,
and the secondary alcohol was mesylated to give 14. Inversion of
the stereochemistry by SN2 substitution of the mesylate with a
phenol, followed by simultaneous deprotection of acid labile
groups revealed pyrrolidinol 15, which reacted with chloride 11
to afford analog 16. Syntheses of other prolinol derivatives shown
in Table 3 can be found in Supplementary data.
Introduction of a trans-t-butoxy group at the 4-position resulted
in 16a, which exhibited high binding affinity for Aurora kinases
and excellent cell activity in the HCT-116 proliferation assay
(IC50 = 8 nM) (Table 3). Consistent with potent inhibition of Aurora
B, 16a also inhibited the histone H3 phosphorylation in HCT-116
cells with an IC50 value of 15 nM and exhibited good kinome selec-
tivity with an S10 score of 0.12. Further expansion of the pyrroli-
dine 4-position SAR ensued. A variety of liphophilic groups were
well tolerated, including difluoro and both diastereoisomers of
mono-fluoro pyrrolidine analogs (16b–16d), along with the large
p-fluorophenoxy substituent (16f). Quite interestingly, the cyclo-
propane-fused pyrrolidine analog (16e) was less well tolerated,
as was t-butylthioether 16h. Introduction of polar groups such as
hydroxyl (16g) or amino (16j) greatly reduced the potency. The
prolinol stereochemistry at 2-position is critical for the Aurora
inhibitory activity, since epimerization of this stereocenter (16g)
led to more than 100-fold loss of cell potency.
We decided empirically to switch the 2-hydroxymethyl group to
the 3-hydroxy group to keep the distance between the hydroxyl
group and the pyrrolidine nitrogen constant. This maneuver re-
sulted in 3,4-trans-disubstituted pyrrolidine compound 17a, which
recapitulated the Aurora binding affinities and cellular potency of
16a, with somewhat decreased kinome selectivity (Table 4). The
in vivo clearance and exposure of 17a in rat iv PK are only margin-
ally better than those of 16a (Table 5). Undeterred by this single
data point, more 3,4-disubstituted pyrrolidine analogs were pre-
pared and characterized.
The synthesis of 3,4-trans-disubstituted pyrrolidines mostly
originated from the appropriately protected 2,5-dihydro-1H-pyr-
role, such as 18, which could be converted to epoxide 19, as shown
in Scheme 4. Epoxide opening with various alcohols and subse-
quent deprotection yielded the requisite pyrrolidine derivatives
20. Alkylation with chloroacetamide 11 yielded the desired analogs
17. Additional manipulations of 2,5-dihydro-1H-pyrroles to access
other pyrrolidines are described in Supplementary data.
Similar to the 2,4-disubstituted pyrrolidine analogs, hydropho-
bic groups at the 4-position of 3,4-trans-disubstituted pyrrolidine
are well tolerated, including variations of the t-butyl group, such
as 17c–17d, 17f–17h (Table 4). Fluoro-substituted (17b) and
methoxyethoxy-substitued analogs (17e) fared worse in the HCT-
116 proliferation assay. Compound 17i demonstrated that the
3-hydroxyl group is not absolutely required; an oxime group at
the same position is almost as potent as 17a. The phenoxy group
in compound 16f was also explored in the context of 3,4-disubsti-
tuted pyrrolidine. p-Fluorophenoxy analog 17l is fivefold more
potent than 16f, and the regiochemistry of the fluorine substitution
(17j–17k) had no effect on cell activity. 2,4- and 3,5-disubstituted
phenoxy analogs (17m–17n) are essentially equipotent to 17l.
The rat PK profile of compound 16a showed high clearance and
low AUC following iv dosing (Table 5). It was hypothesized that the
primary hydroxyl group might be a cause for the high clearance.
Table 2
SAR of aminoacetamide analogs for Aurora kinases
NH
N
N
HN
H
N
NR1R2
O
N
N
S
12a-12e
NR1R2
Aurora Kd (nM)
Cell IC50 (nM)
pHH3 (HCT-116) Proliferation (HCT-116)
Kinase specificity S10
a
a
Entry
A
B
C
H
N
12a
12b
32
41
6
288
655
364
365
0.25
0.16
H
N
143
42
14
N
N
12c
12d
85
31
41
8
17
5
1830
293
1840
370
0.10
0.14
O
OH
12e
14
4
1
146
148
0.20
N
a
Each experiment was run in duplicate and the values shown are the average of the two.

S. Abraham et al. / Bioorg. Med. Chem. Lett. 21 (2011) 5296–5300
5299
Table 3
Table 4
SAR of pyrrolidinoacetamide analogs for Aurora kinases
SAR of pyrrolidinoacetamide analogs for Aurora kinases
NH
NH
N
N
N
N
HN
HN
H
N
H
N
R
R
N
N
O
N
O
N
S
S
16a-16j
17a-17o
a
a
a
a
Entry Rc
Aurora Kd
(nM)
Cell IC50 (nM)
Kinase
specificity
score
Entry Rc
Aurora Kd
(nM)
Cell IC50 (nM)
Kinase
specificity
score
A
B
C
pHH3
(HCT-
116)
Proliferation
(HCT-116)
A
B
C
pHH3 Proliferation
(HCT- (HCT-116)
116)
S(10)
S(10)
OH
OH
N
17a
17b
17c
12
5
5
1
4
NDb 16
4
33
9
0.22
0.21
0.27
N
16a
16b
16c
16d
16e
9
8
8
5
9
4
2
15
8
25
0.12
0.28
0.20
0.23
0.18
O
O
OH
OH
N
N
OH
ND
ND
47
27
F
N
2
29
91
F
6
F
O
CF3
OH
OH
N
N
15
8
NDb
ND
104
25
N
N
N
17d
8
4
ND
28
9
0.21
O
O
F
OH
OH
17e
17f
5
8
2
4
2
4
5
ND
ND
ND
ND
ND
49
23
23
23
28
25
10
10
6
0.22
0.20
0.27
0.26
0.15
28
O
OH
F
OH
N
N
O
O
H
17 15 ND
53 21 ND
301 69 ND
179
203
OH
H
OH
17g
17h
17id
7
OH
N
N
N
16f
78
24
0.15
11
9
O
O
F
OH
OH
N
N
N
8
16g
2490
2390
0.007
O
O
OH
OH
17j
10
9
ND
28
4
0.35
O
F
N
16h
16i
16j
111 39 ND
58 15 ND
1790
637
1610
596
0.08
OH
N
S
17k
17l
O
17 10 ND
51
44
58
7
5
5
0.31
0.25
0.29
OH
F
N
N
0.115
0.103
OH
OH
N
N
OH
OH
15
8
ND
O
O
F
F
381 144 ND 15,000
4700
17m
13 17 ND
26 21 ND
NH2
F
a
OH
Each experiment was run in duplicate and the values shown are the average of
the two.
N
N
F
F
17n
17o
51
84
7
9
0.36
b
O
ND = not determined.
Single enantiomer.
c
OH
7
8
ND
0.201
O
F
Subtle differences in kinome selectivity for these analogs were ob-
served, with 17l exhibiting a slightly better selectivity score. The
cis-isomer of 17l (17o) was also evaluated, and was found to pos-
sess virtually the same in vitro profile as the trans-isomer 17l.
Rat PK was used as a screening model to assess the feasibility of
dosing compounds in vivo. The PK profiles of select compounds are
shown in Table 5. In comparison to 1, primary alcohol analog 16a
and secondary alcohol analog 17a both showed elevated clearance
and reduced exposure following intravenous (iv) dosing. Com-
pound 17l showed clearance similar to the original lead 1, and
improved exposure over both 16a and 17a. Good exposure of 17l
a
Each experiment was run in duplicate and the values shown are the average of
the two.
b
ND = not determined.
Racemic mixture.
A mixture of E and Z isomers.
c
d
line. The compound was dosed intraperitoneally BID using 50%
PEG/water as vehicle. Even though substantial dose-dependent
tumor growth inhibition was observed (comparable antitumor activ-
ity to positive control compound, VX-680), severe body weight loss
(>20%) in the high dose group (37.5 mg/kg dosed BID for eight
days) complicated the interpretation of the pharmacological effect.
A number of factors might have influenced the outcome of the
xenograft study, including route of administration, vehicle used
In SCID mice was also achieved with an AUC value of 47.48
following a single 60 mg/kg intraperitoneal (ip) dose.
lMÁh
The antitumor efficacy of 17l was assessed in a subcutaneous
flank-tumor xenograft model in nude mice using the HCT-116 cell

5300
S. Abraham et al. / Bioorg. Med. Chem. Lett. 21 (2011) 5296–5300
NH
N
N
Supplementary data
O
O
O N
HN
H
N
b,c
a
d
HN
O
N
OH
OR
tert
N
OH
OR
N
N
O
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.bmcl.2011.07.027.
O
S
18
19
20a
20d R
R
=
=
-
Butyl
17a
R
17d R
=
=
tert-Butyl
C(Me)2CH2CH3
20e R = CH2CH2OCH3
CH(Me)2CH2CH3
17e R = CH2CH2OCH3
References and notes
20f
R
20g R
=
Isopropyl
17f R
=
Isopropyl
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= Methyl
17g
R
= Methyl
cyclopropyl
20h Cyclopentyl
cyclopropyl
17h
= Cyclopentyl
R
=
R
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Scheme 4. Reagents and conditions: (a) mCPBA, DCM, rt, 52%; (b) ROH, B(C6F5)3,
DCM, 90 °C, 5 h; (c) Pd(OH)2, H2, MeOH, ca. 56% over two steps; (d) 11, KI, DIEA,
DMF, 70 °C, 3 h, 23–62%.
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Table 5
Intravenous rat PK profiles for compounds 1, 9e, 16a, 17a, 17la,b
Compds
Clearance
(mL/min/kg)
Volume of distribution
(L/kg)
Half life
(h)
AUC
MÁh)
(l
1
9e
16a
17a
17l
28.5
53.3
52.2
45
2.15
5.86
9.77
18.3
2.93
10.8
8.66
15.4
11.2
3.36
2.34
0.757
0.581
0.644
1.17
25.2
a
1 mg/kg dosed intravenously.
Sprague Dawley rat, PEG400/water as vehicle.
10. Abraham, S.; Chao, Q.; Hadd, M. J.; Holladay, M. W.; Liu, G.; Nambu, M. D.; Setti,
E. WO201002472, 2010.
b
11. The compounds described herein were tested for their binding affinity to the
catalytic domain of Aurora kinases in a competition binding assay with an ATP-
competitive Aurora inhibitor bound to a solid surface as described in the
following reference: Fabian, M. A.; Biggs, W. H., III; Treiber, D. K.; Atteridge, C.
E.; Azimioara, M. D.; Benedetti, M. G.; Carter, T. A.; Ciceri, P.; Edeen, P. T.; Floyd,
M.; Ford, J. M.; Galvin, M.; Gerlack, J. L.; Grotzfeld, R. M.; Herrgard, S.; Insko, D.
E.; Insko, M. A.; Lai, A. G.; Lelias, J.-M.; Mehta, S. A.; Milanov, Z. V.; Velasco, A.
M.; Wodicka, L. M.; Patel, H. K.; Zarrinkar, P. P.; Lockhart, D. J. Nat. Biotechnol.
2005, 23, 329.
in the study, dosing schedule, strain of animals, and the possibility
of intrinsic toxicity of the lead compounds. Further efforts to im-
prove the overall profiles of the lead compound 17l will be re-
ported in due course.
In summary, introduction of basic amines to the
a-position
of the carboxamide terminus of lead compound 1 resulted in
analogs with high cellular activity and improved rat PK profiles.
Particularly, compound 17l serves as an excellent lead molecule
for further optimization of the overall properties of this series of
pan-Aurora kinase inhibitors.
12. Selectivity score or S(10) is the ratio of kinase targets of the compound to the
total number of kinases screened at a 10 lM compound concentration; kinases
were defined as targets if the primary screen showed >90% competition. See
the following reference for details regarding the calculation of S(10) score:
Karaman, M. W.; Herrgard, S.; Treiber, D. K.; Gallant, P.; Atteridge, C. E.;
Campbell, B. T.; Chan, K. W.; Ciceri, P.; Davis, M. I.; Edeen, P. T.; Faraoni, R.;
Floyd, M.; Hunt, J. P.; Lockhart, D. J.; Milanov, Z. V.; Morrison, M. J.; Pallares, G.;
Patel, H. K.; Pritchard, L. M.; Wodicka, L. M.; Zarrinkar, P. P. Nat. Biotechnol.
2008, 26, 127.
Acknowledgment
13. (a) Schindler, T.; Bornmann, W.; Pellicena, P.; Miller, W. T.; Clarkson, B.;
Kuriyan, J. Science 2000, 289, 1938; (b) Nagar, B.; Bornmann, W. G.; Pellicena,
P.; Schindler, T.; Veach, D. R.; Miller, W. T.; Clarkson, B.; Kuriyan, J. Cancer Res.
2002, 62, 4236.
We thank the KinomeScan group at Ambit Biosciences (now a
division of DiscoveRX) for generating Aurora Kds and kinase spec-
ificity scores.