U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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

Molecular Formula C13H17N6O7P
Molecular Weight 400.2838
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including http://www.enzolifesciences.com/BML-EI332/triciribine/ https://www.ncbi.nlm.nih.gov/pubmed/20644979 http://www.apexbt.com/triciribine.html

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

Curator's Comment: Triciribine phosphate (TCN-P, NSC-280594) is a nucleotide derivative first synthesized by Schram and Townsend, University of South Florida, in 1971 https://www.ncbi.nlm.nih.gov/pubmed/20644979

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
350 mg/m2 1 times / 3 weeks multiple, intravenous
Highest studied dose
Dose: 350 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 350 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, ADULT
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Disc. AE: Liver damage...
AEs leading to
discontinuation/dose reduction:
Liver damage (grade 4-5)
Sources:
30 mg/m2 1 times / day multiple, intravenous
MTD
Dose: 30 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 30 mg/m2, 1 times / day
Sources: Page: p.256, 257
unhealthy, ADULT
n = 10
Health Status: unhealthy
Condition: breast cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 10
Sources: Page: p.256, 257
DLT: Hypertriglyceridemia...
Dose limiting toxicities:
Hypertriglyceridemia (grade 3-4, 10%)
Sources: Page: p.256, 257
55 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 55 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 55 mg/m2, 1 times / week
Sources: Page: p.6
unhealthy, ADULT
n = 9
Health Status: unhealthy
Condition: Hematological tumors
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 9
Sources: Page: p.6
40 mg/m2 1 times / day multiple, intravenous
Studied dose
Dose: 40 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 40 mg/m2, 1 times / day
Sources: Page: p.256, 257
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: breast cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.256, 257
DLT: Hyperglycemia...
Disc. AE: Hypertriglyceridemia...
Dose limiting toxicities:
Hyperglycemia (grade 3-4, 60%)
AEs leading to
discontinuation/dose reduction:
Hypertriglyceridemia (grade 3, 20%)
Sources: Page: p.256, 257
65 mg/m2 1 times / week multiple, intravenous
Studied dose
Dose: 65 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 65 mg/m2, 1 times / week
Sources: Page: p.6
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: Hematological tumors
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources: Page: p.6
DLT: Triglyceride increased, Lipase increased...
Dose limiting toxicities:
Triglyceride increased (14.3%)
Lipase increased (grade 3-4, 28.6%)
Sources: Page: p.6
AEs

AEs

AESignificanceDosePopulation
Liver damage grade 4-5
Disc. AE
350 mg/m2 1 times / 3 weeks multiple, intravenous
Highest studied dose
Dose: 350 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 350 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, ADULT
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Hypertriglyceridemia grade 3-4, 10%
DLT
30 mg/m2 1 times / day multiple, intravenous
MTD
Dose: 30 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 30 mg/m2, 1 times / day
Sources: Page: p.256, 257
unhealthy, ADULT
n = 10
Health Status: unhealthy
Condition: breast cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 10
Sources: Page: p.256, 257
Hypertriglyceridemia grade 3, 20%
Disc. AE
40 mg/m2 1 times / day multiple, intravenous
Studied dose
Dose: 40 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 40 mg/m2, 1 times / day
Sources: Page: p.256, 257
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: breast cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.256, 257
Hyperglycemia grade 3-4, 60%
DLT
40 mg/m2 1 times / day multiple, intravenous
Studied dose
Dose: 40 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 40 mg/m2, 1 times / day
Sources: Page: p.256, 257
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: breast cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.256, 257
Triglyceride increased 14.3%
DLT, Disc. AE
65 mg/m2 1 times / week multiple, intravenous
Studied dose
Dose: 65 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 65 mg/m2, 1 times / week
Sources: Page: p.6
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: Hematological tumors
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources: Page: p.6
Lipase increased grade 3-4, 28.6%
DLT, Disc. AE
65 mg/m2 1 times / week multiple, intravenous
Studied dose
Dose: 65 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 65 mg/m2, 1 times / week
Sources: Page: p.6
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: Hematological tumors
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources: Page: p.6
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Activity of triciribine and triciribine-5'-monophosphate against human immunodeficiency virus types 1 and 2.
1993 Apr
Deoxy sugar analogues of triciribine: correlation of antiviral and antiproliferative activity with intracellular phosphorylation.
2000 Jun 15
Synthesis and antiviral activity of 2-substituted analogs of triciribine.
2003 Dec
Synthesis of new 2'-beta-C-methyl related triciribine analogues as anti-HCV agents.
2004 Jul 5
Design, synthesis and antiviral activity of novel 4,5-disubstituted 7-(beta-D-ribofuranosyl)pyrrolo[2,3-d][1,2,3]triazines and the novel 3-amino-5-methyl-1-(beta-D-ribofuranosyl)- and 3-amino-5-methyl-1-(2-deoxy-beta-D-ribofuranosyl)-1,5-dihydro-1,4,5,6,7,8-hexaazaacenaphthylene as analogues of triciribine.
2005 Jun 2
1-Nitropyrene stabilizes the mRNA of cytochrome P450 1a1, a carcinogen-metabolizing enzyme, via the Akt pathway.
2009 Dec
High-throughput screening compatible cell-based assay for interrogating activated notch signaling.
2009 Feb
Inhibition of human immunodeficiency virus type 1 by triciribine involves the accessory protein nef.
2010 Apr
Preclinical testing of the Akt inhibitor triciribine in T-cell acute lymphoblastic leukemia.
2011 Mar
Ursodeoxycholic acid suppresses mitochondria-dependent programmed cell death induced by sodium nitroprusside in SH-SY5Y cells.
2012 Feb 26
Inhibitory roles of prohibitin and chemerin in FSH-induced rat granulosa cell steroidogenesis.
2013 Feb
Piceatannol suppresses the metastatic potential of MCF10A human breast epithelial cells harboring mutated H-ras by inhibiting MMP-2 expression.
2013 Oct
Insulin attenuates arsenic-induced neurite outgrowth impairments by activating the PI3K/Akt/SIRT1 signaling pathway.
2015 Aug 5
Patents

Sample Use Guides

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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:34:54 GMT 2023
Edited
by admin
on Fri Dec 15 15:34:54 GMT 2023
Record UNII
5L5GE3DV88
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TRICIRIBINE PHOSPHATE
USAN   WHO-DD  
USAN  
Official Name English
3-AMINO-1,5-DIHYDRO-5-METHYL-1-.BETA.-D-RIBOFURANOSYL-1,4,5,6,8-PENTAAZAACENAPHTHYLENE 5'-(DIHYDROGEN PHOSPHATE)
Common Name English
TRICIRIBINE PHOSPHATE [USAN]
Common Name English
Triciribine phosphate [WHO-DD]
Common Name English
NSC-280594
Code English
Classification Tree Code System Code
NCI_THESAURUS C2254
Created by admin on Fri Dec 15 15:34:54 GMT 2023 , Edited by admin on Fri Dec 15 15:34:54 GMT 2023
NCI_THESAURUS C2087
Created by admin on Fri Dec 15 15:34:54 GMT 2023 , Edited by admin on Fri Dec 15 15:34:54 GMT 2023
NCI_THESAURUS C1556
Created by admin on Fri Dec 15 15:34:54 GMT 2023 , Edited by admin on Fri Dec 15 15:34:54 GMT 2023
FDA ORPHAN DRUG 558516
Created by admin on Fri Dec 15 15:34:54 GMT 2023 , Edited by admin on Fri Dec 15 15:34:54 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C1262
Created by admin on Fri Dec 15 15:34:54 GMT 2023 , Edited by admin on Fri Dec 15 15:34:54 GMT 2023
PRIMARY
PUBCHEM
43860
Created by admin on Fri Dec 15 15:34:54 GMT 2023 , Edited by admin on Fri Dec 15 15:34:54 GMT 2023
PRIMARY
EPA CompTox
DTXSID30210993
Created by admin on Fri Dec 15 15:34:54 GMT 2023 , Edited by admin on Fri Dec 15 15:34:54 GMT 2023
PRIMARY
FDA UNII
5L5GE3DV88
Created by admin on Fri Dec 15 15:34:54 GMT 2023 , Edited by admin on Fri Dec 15 15:34:54 GMT 2023
PRIMARY
CAS
61966-08-3
Created by admin on Fri Dec 15 15:34:54 GMT 2023 , Edited by admin on Fri Dec 15 15:34:54 GMT 2023
PRIMARY
MESH
C014205
Created by admin on Fri Dec 15 15:34:54 GMT 2023 , Edited by admin on Fri Dec 15 15:34:54 GMT 2023
PRIMARY
ChEMBL
CHEMBL462018
Created by admin on Fri Dec 15 15:34:54 GMT 2023 , Edited by admin on Fri Dec 15 15:34:54 GMT 2023
PRIMARY
DRUG BANK
DB14636
Created by admin on Fri Dec 15 15:34:54 GMT 2023 , Edited by admin on Fri Dec 15 15:34:54 GMT 2023
PRIMARY
NSC
280594
Created by admin on Fri Dec 15 15:34:54 GMT 2023 , Edited by admin on Fri Dec 15 15:34:54 GMT 2023
PRIMARY
Related Record Type Details
SOLVATE->ANHYDROUS
Related Record Type Details
ACTIVE MOIETY