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Details

Stereochemistry ABSOLUTE
Molecular Formula C13H17N6O7P
Molecular Weight 400.2838
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRICIRIBINE PHOSPHATE

SMILES

CN1N=C(N)C2=CN([C@@H]3O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]3O)C4=NC=NC1=C24

InChI

InChIKey=URLYINUFLXOMHP-HTVVRFAVSA-N
InChI=1S/C13H17N6O7P/c1-18-11-7-5(10(14)17-18)2-19(12(7)16-4-15-11)13-9(21)8(20)6(26-13)3-25-27(22,23)24/h2,4,6,8-9,13,20-21H,3H2,1H3,(H2,14,17)(H2,22,23,24)/t6-,8-,9-,13-/m1/s1

HIDE SMILES / InChI

Description

Triciribine is a purine analogue which inhibits DNA and protein synthesis, it is a synthetic tricyclic nucleoside which acts as a specific inhibitor of the Akt signaling pathway. It selectively inhibits the phosphorylation and activation of Akt1, -2 and -3 but does not inhibit Akt kinase activity nor known upstream Akt activators such as PI 3-Kinase and PDK1. It inhibits cell growth and induces apoptosis preferentially in cells that express aberrant Akt1. In whole cells triciribine is phosphorylated by adenosine kinase which may be necessary for its activity. Triciribine is a cancer drug which was first synthesised in the 1970s and trialled clinically in the 1980s and 1990s without success. Following the discovery in the early 2000s that the drug would be effective against tumours with hyperactivated Akt, it is now again under consideration in a variety of cancers. As PTX-200, the drug is currently in two early stage clinical trials in breast cancer and ovarian cancer being conducted by the small molecule drug development company Prescient Therapeutics.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
130.0 nM [IC50]
20.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
5.28 μM
15 mg/m² 3 times / 4 weeks multiple, intravenous
TRICIRIBINE PHOSPHATE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
97 μM × h
15 mg/m² 3 times / 4 weeks multiple, intravenous
TRICIRIBINE PHOSPHATE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
89.2 h
55 mg/m² 1 times / day multiple, intravenous
TRICIRIBINE blood
Homo sapiens
27.7 h
15 mg/m² 3 times / 4 weeks multiple, intravenous
TRICIRIBINE PHOSPHATE plasma
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

PubMed

Sample Use Guides

In Vivo Use Guide
15 mg/m^2 intravenous (IV) Weekly Over 1 Hour On Days 1, 8, and 15.
Route of Administration: Intravenous
In Vitro Use Guide
Triciribine (1 uM) totally inhibited the growth of L1210 cells in culture and caused progressive loss of cellular viability, as indicated by a decreased clonogenicity and nigrosin dye exclusion.