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
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
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 |
DescriptionSources: http://adisinsight.springer.com/drugs/800001937Curator'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
Sources: http://adisinsight.springer.com/drugs/800001937
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
Sources: http://adisinsight.springer.com/drugs/800001937
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
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4282 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20644979 |
130.0 nM [IC50] | ||
Target ID: CHEMBL378 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7685612 |
20.0 nM [IC50] | ||
Target ID: CHEMBL380 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7685612 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Doses
Dose | Population | Adverse 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 todiscontinuation/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%) Sources: Page: p.6Lipase increased (grade 3-4, 28.6%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 |
PubMed
Title | Date | PubMed |
---|---|---|
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
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00642031
15 mg/m^2 intravenous (IV) Weekly Over 1 Hour On Days 1, 8, and 15.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/4063986
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
Edited
Fri Dec 15 15:34:54 GMT 2023
by
admin
on
Fri Dec 15 15:34:54 GMT 2023
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Record UNII |
5L5GE3DV88
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Record Status |
Validated (UNII)
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Record Version |
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-
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NCI_THESAURUS |
C2254
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NCI_THESAURUS |
C2087
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NCI_THESAURUS |
C1556
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FDA ORPHAN DRUG |
558516
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C1262
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43860
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DTXSID30210993
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5L5GE3DV88
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61966-08-3
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C014205
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CHEMBL462018
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DB14636
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280594
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PRIMARY |
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