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Drug-Target Interaction

Drug

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PubChem ID:3032771
Structure:
Synonyms:
22457-89-2
8088 C.B
8088 C.B.
B9636_SIGMA
benfothiamine
Benfotiamina [INN-Spanish]
BENFOTIAMINE
Benfotiamine [DCF:INN:JAN]
Benfotiamine [INN:DCF:JAN]
Benfotiaminum [INN-Latin]
Benphothiamine
Benzoic acid, thio-, S-ester with
Benzoic acid, thio-, S-ester with N-((4-amino-2-methyl-5-pyrimidinyl)methyl)-N-(4-hydroxy-2-mercapto-1-methyl-1-butenyl)formamide dihydrogen phosphate (ester)
Benzoylthiamine monophosphate
Benzoylthiamine O-monophosphate
Berdi
Betivina
Biotamin
BPBio1_000757
BRN 0771326
BSPBio_000687
BTMP
BTMP-benfo
C19H23N4O6PS
CB 8088
EINECS 245-013-4
LS-38336
N-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-N-(4-hydroxy-2-mercapto-1-methyl-1-butenyl)formamide S-benzoate O-phosphate
NCGC00179477-01
Neurostop
Nitanevril
Prestwick2_000654
Prestwick3_000654
Prestwick_68
S-Benzoylthiamine monophosphate
S-Benzoylthiamine O-monophosphate
ST056187
Tabiomyl
Thiamine monophosphate benzoyl
Vitanevril
ATC-Codes:

Target

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Uniprot ID:AKT1_MOUSE
Synonyms:
AKT1 kinase
C-AKT
PKB
Protein kinase B
RAC-alpha serine/threonine-protein kinase
RAC-PK-alpha
Thymoma viral proto-oncogene
EC-Numbers:2.7.11.1
Organism:Mouse
Mus musculus
PDB IDs:-

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----

References:

16416271
Benfotiamine accelerates the healing of ischaemic diabetic limbs in mice through protein kinase B/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis.. S Gadau; C Emanueli; S Van Linthout; G Graiani; M Todaro; M Meloni; I Campesi; G Invernici; F Spillmann; K Ward; P Madeddu (2006) Diabetologia display abstract
AIMS/HYPOTHESIS: Benfotiamine, a vitamin B1 analogue, reportedly prevents diabetic microangiopathy. The aim of this study was to evaluate whether benfotiamine is of benefit in reparative neovascularisation using a type I diabetes model of hindlimb ischaemia. We also investigated the involvement of protein kinase B (PKB)/Akt in the therapeutic effects of benfotiamine. METHODS: Streptozotocin-induced diabetic mice, given oral benfotiamine or vehicle, were subjected to unilateral limb ischaemia. Reparative neovascularisation was analysed by histology. The expression of Nos3 and Casp3 was evaluated by real-time PCR, and the activation state of PKB/Akt was assessed by western blot analysis and immunohistochemistry. The functional importance of PKB/Akt in benfotiamine-induced effects was investigated using a dominant-negative construct. RESULTS: Diabetic muscles showed reduced transketolase activity, which was corrected by benfotiamine. Importantly, benfotiamine prevented ischaemia-induced toe necrosis, improved hindlimb perfusion and oxygenation, and restored endothelium-dependent vasodilation. Histological studies revealed the improvement of reparative neovascularisation and the inhibition of endothelial and skeletal muscle cell apoptosis. In addition, benfotiamine prevented the vascular accumulation of advanced glycation end products and the induction of pro-apoptotic caspase-3, while restoring proper expression of Nos3 and Akt in ischaemic muscles. The benefits of benfotiamine were nullified by dominant-negative PKB/Akt. In vitro, benfotiamine stimulated the proliferation of human EPCs, while inhibiting apoptosis induced by high glucose. In diabetic mice, the number of circulating EPCs was reduced, with the deficit being corrected by benfotiamine. CONCLUSIONS/INTERPRETATION: We have demonstrated, for the first time, that benfotiamine aids the post-ischaemic healing of diabetic animals via PKB/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis. In addition, benfotiamine combats the diabetes-induced deficit in endothelial progenitor cells.