AEG Electrolux COMPETENCE 5133 V User Manual Page 19
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Metabolic stabilit
y
y
Condition Incuba
t
ion
t
ime
(
h
)
Mean % from
T
0 Condition
Incuba
t
ion
t
i
me
(h
)
Mean % from
T
0 Condition
Incuba
t
ion
t
i
me
(h
)
Concen
t
ra
t
ion
(
µ
M)
%from
T
0
Incubation of
O
RI-M4-01
w
ith li
v
er microsomes at 10 µM Positif Controls Stability control
Human Human
Concen
t
ra
t
ion
(
µ
M
)
Peak area
(
coun
t
s
)
(
)
t
i
me
(h
)
t
i
me
(h
)
(
µ
M)
0 5.92 6.60 6.26 100.00 0 807850 822904 815377 100.00 06.88100.00
1 3.60 3.83
3.72 59.34
4 282115 289708
285912 35.06
46.89
100.22
4 3.54 3.53 3.54 56.48
0 6.17 6.97 6.57 100.00
4 6.27 6.76 6.52 99.22
(
µ
)
(
)
with NADPH
Omeprazol (0.5µM)
without
microsomes
without NADPH
Incubation of ORI-M4-01 with liver microsomes (presence
NADPH)
human T0
Human T1h
Condition Incubation time (h) Mean % from T0 Condition
Incuba
t
ion
time (h)
Mean % from T0
0 6.53 6.82 6.68 100.00 0 784238 776276 780257 100.00
1 0.66 0.71 0.69 10.27 4 88662 90145 89403 11.46
4 0.55 0.09 0.32 4.77
Mou
s
e Mou
s
e
Concentration (µM) Peak area (counts)
with NADPH
Omeprazol (0.5µM)
80
100
120
human T4h
Mouse T0
Mouse T1h
Mouse T4h
Rat T0
Rat T1h
0 5.33 6.30 5.82 100.00
4 6.32 6.12 6.22 106.90
Condition Incubation time (h) Mean % from T0 Condition
Incuba
t
ion
t
i
me
(h
)
Mean % from T0
without NADPH
Rat Rat
Concentration (µM) Peak area (counts)
40
60
% from T0
Rat T4h
t
i
me
(h
)
0 6.47 6.07 6.27 100.00 0 753875 779072 766473 100.00
1 1.47 1.56 1.52 24.20 4 57602 59998 58800 7.67
4 1.15 1.32 1.23 19.65
0 6.46 6.50 6.48 100.00
4 6.12 6.63 6.38 98.39
without NADPH
with NADPH
Omeprazol (0.5µM)
0
20
Incubation
www.m4.de
One ste
p
F introduction
p
• onestepreactionfromstable
intermediate
byproductA
• desiredF‐productformed
• by‐productsknown
•
can be separated
HPLC
byproductB
•
can
be
separated
HPLC
• adaptationandoptimisationfor
18Fhotlabelling
• alternativel
y
11C
p
robabl
y
doable
F‐product
y py
www.m4.de
Second
y
ear outcome
y
• sufficientpotencyonLRRK2lownMorbetter
• verygoodLRRK2selectivity
• verygoodtargetengagementinvitro
•
g
oodbrain
p
enetration
g p
• sufficientbrainfreefraction
• lateintroductionof
11
Cand
18
Fareviableoptions
•
extra optimization loop solved efflux problem
•
extra
optimization
loop
solved
efflux
problem
• cold“markerchemistry” established
• radiochemistryandPETcollaborationwithProf.GildehausandProf.
Bartenstein Nuklearmedizin LMU
www.m4.de
Bartenstein
,
Nuklearmedizin
,
LMU
We welcome you at
www.origenis.com
origenis GmbH
Am Klopferspitz 19a
82152 Martinsried
Germany
Tel. +49-89-7801676-0
Fax +49-89-7801676-777
16
- Strategieworkshop 1
- Biobank Alliance & 2
- Trial Service Center 2
- Agenda 4
- Vortragsplan m 5
- Stand 17.03.2014 6
- Biobank Alliance 9
- NeoExNET 11
- ZieledesProjektes(I) 13
- ZieledesProjektes(II) 13
- Albertsetal. 2002 15
- • Biopsien 16
- Blutentnahme 16
- • Fragebogen 16
- • DNA Sequenzierung ongoing 17
- • WGA und WTA 17
- March 2014 18
- % from T0 19
- Incubation 19
- Evotec Munich 20
- PM24 Suche von Schizo 21
- Projektpartner: GeneWake GmbH 23
- Projektpartner: 24
- Leukemia‐peptide 27
- TCR-isolation 28
- Christian Simmet 32
- , Angelika Schnieke 32
- , Eckhard Wolf 32
- Was haben wir erreicht? 33
- Trial Service Cente 34
- etabliert; aktiv 36
- PI3KPrüfzentren 37
- MEKPrüfzentren 37
- Total cMET (%) 38
- • Biomarker fü 40
- Patienten 42
- 2) Arzneimittelhersteller 42
- Ergebnisse 43
- Fibrosis[%] 44
- Projektziele 45
- LineAssay 47
- Hp Protease 47
- Projektpartner 50
- PhotoofCOAALA‐MOUSE 51
- Histology 51
- T17: Strukturbasierte 53
- Antikörpercharakterisierung 53
- München, 19. März 2014 54
- Patentanmeldung: 55
- Publikationen: 55
- Präklinisch 56
- T2w-MRI DWI-MRI 57
- Projektziele in PM8 58
- Introduction 59
- Scouting & Incubation: 61
- NanoTemper Technologies GmbH 62
- Querschnitt 63
- QuantitativeAnalyse 64
- CRELUX & 4SC Discovery 64
- • Neue Forschun 67
- • Generischer 68
- T cell antibodies 69
- Notizen 80
- Biomarker Conference 81
- Competence in 82
- Biotechnology 82
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