The document discusses the role of protein kinase B (Akt) in various physiological functions, including glucose metabolism, cell survival, and cancer progression. It outlines the differences between Akt isoforms (Akt1, Akt2, Akt3) and their specific involvement in signaling pathways, apoptosis, and the Warburg effect in cancer cells. Additionally, the document highlights ongoing clinical trials for Akt inhibitors as potential cancer therapies.

1. 1

2. PRESENTED BY- AMEENA
MEHABOOB
AKT (PROTEIN KINASE
B)
2

3. INTRODUCTION
Serine/ threonine specific protein kinase.
Plays a key role in-
 Glucose metabolism
 Cell proliferation
 Transcription
 Cell migration
3

4. TYPES
AKT1 AKT2
AKT3
4

5. PHYSIOLOGICAL FUNCTIONS5

6. AKT1
BLOCKS
APOPTOSIS.
MAJOR FACTOR IN
SEVERAL TYPES OF
CANCER
MOUSE MODEL WITH
COMPLETE DELETION OF
AKT1 GROWTH
RETARDATION,
INCREASED
SPONTANEOUS
APOPTOSIS IN TISSUES
CELL
SURVIVAL
PATHWAYS
6

7. AKT2
INSULIN SIGNALING
PATHWAY
SIGNALING
MOLECULE
MOUSE
WITHOUT
AKT1,
WITH AKT2
GLUCOSE
HOMEOSTASIS
NORMAL
SMALLER
IN SIZE
MOUSE WITH
AKT1,
WITHOUT
AKT2
MILD
GROWTH
DEFICIENCY
INSULIN
RESISTANCE
7

8. AKT3
ROLE
LESS
CLEAR
PREDOMINANT
LY EXPRESSED
IN BRAIN
MOUSE
LACKING
AKT3- SMALL
BRAIN
8

9. NAME
• TEMPORARY CLASSIFICATION
OF MICE WHICH DEVELOPED
THYMIC LYMPHOMAAk
• THYMOMA
t
9

10. SIGNALING PATHWAY AND PHARMACOLOGICAL
IMPLICATIONS10

11. Akt signaling pathway in metabolism, apoptosis,
proliferation
Initial
stimulatio
n by
growth
factor
Activation
of cell
surface
receptor &
phosphoryl
ation of
PI3K
Phosphor
ylates
lipids on
plasma
membran
e
Forms 2nd
messenger
PIP3
Akt is
activated
Mediates cell
growth,
survival,
angiogenesis
11

12. Regulation
12

13. ROLE IN CANCER
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14. Angiogenesis
 Angiogenesis, the formation of new blood
vessels, is often critical for tumour cells to
survive and grow in nutrient-depleted
conditions.
 Akt is activated downstream of vascular
endothelial growth factor (VEGF)
in endothelial cells in the lining of blood
vessels, promoting survival and growth.
14

15. Glucose metabolism
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 In cancer cells, an increase in Akt signaling
correlates with an increase in glucose
metabolism, compared to normal cells.
 Cancer cells favor glycolysis for energy
production over mitochondrial oxidative
phosphorylation, even when oxygen supply is
not limited. This is known as the Warburg
effect, or aerobic glycolysis.

16. THERAPEUTIC POTENTIAL16

17. 17
CANCER

18. 18
PROTEUS SYNDROME

19. Akt INHIBITORS
19
PRODUCT NAME INFORMATION PHASE OF CLINICAL
TRIAL
ARQ 092 Akt1 inhibitor for Proteus
syndrome
Phase 0 dose finding trial in
Nov 2015
Perifosine (KRX-0401) Novel Akt inhibitor
Phase 3
MK-2206 Allosteric Akt inhibitor Phase 2
Ipatasertib (GDC-0068)
Highly selective, targets Akt
1/2/3
Phase 2 in 2014
Afuresertib
Potent, orally available Akt
inhibitor for Akt1, Akt2 and
Phase 2 in 2015

20. 20
APPROVED Akt INHIBITOR- MILTEFOSINE
 Any form of leishmaniasis
 Can be used in the treatment of
primary amoebic
meningoencephalitis

21. REFERENCES
 www.wikipedia.com
 www.cancer.gov
 www.invivogen.com
 www.cancernetwork.com
 www.myelomabeacon.com
 www.pharmaceuticalintelligence.com
 www.arqule.com
 www.clinicaltrials.gov
 www.nature.com
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