TRICIRIBINE PHOSPHATE

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 Search

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
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

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serine/threonine-protein kinase AKT 29 Target ID: CHEMBL4282 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20644979	Inhibitor 8297	130.0 nM [IC50]
Human immunodeficiency virus 1 33 Target ID: CHEMBL378 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7685612	Inhibitor 8297	20.0 nM [IC50]
Human immunodeficiency virus 2 3 Target ID: CHEMBL380 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7685612	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Acute leukemia 31 Sources: https://clinicaltrials.gov/ct2/show/NCT02930109	Primary	Phase II 1132	Unknown Approved Use Unknown
Breast cancer 434 Sources: http://adisinsight.springer.com/drugs/800001937	Primary	Phase II 1132	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: http://adisinsight.springer.com/drugs/800001937	Primary	Phase II 1132	Unknown Approved Use Unknown

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: https://pubmed.ncbi.nlm.nih.gov/6825123	unhealthy, ADULT Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/6825123	Disc. AE: Liver damage... AEs leading to discontinuation/dose reduction: Liver damage (grade 4-5) Sources: https://pubmed.ncbi.nlm.nih.gov/6825123
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: https://pubmed.ncbi.nlm.nih.gov/8529286 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: https://pubmed.ncbi.nlm.nih.gov/8529286 Page: p.256, 257	DLT: Hypertriglyceridemia... Dose limiting toxicities: Hypertriglyceridemia (grade 3-4, 10%) Sources: https://pubmed.ncbi.nlm.nih.gov/8529286 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: https://pubmed.ncbi.nlm.nih.gov/23993427 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: https://pubmed.ncbi.nlm.nih.gov/23993427 Page: p.6	Sources: https://pubmed.ncbi.nlm.nih.gov/23993427 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: https://pubmed.ncbi.nlm.nih.gov/8529286 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: https://pubmed.ncbi.nlm.nih.gov/8529286 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: https://pubmed.ncbi.nlm.nih.gov/8529286 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: https://pubmed.ncbi.nlm.nih.gov/23993427 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: https://pubmed.ncbi.nlm.nih.gov/23993427 Page: p.6	DLT: Triglyceride increased, Lipase increased... Dose limiting toxicities: Triglyceride increased (14.3%) Lipase increased (grade 3-4, 28.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/23993427 Page: p.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: https://pubmed.ncbi.nlm.nih.gov/6825123	unhealthy, ADULT Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/6825123
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: https://pubmed.ncbi.nlm.nih.gov/8529286 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: https://pubmed.ncbi.nlm.nih.gov/8529286 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: https://pubmed.ncbi.nlm.nih.gov/8529286 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: https://pubmed.ncbi.nlm.nih.gov/8529286 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: https://pubmed.ncbi.nlm.nih.gov/8529286 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: https://pubmed.ncbi.nlm.nih.gov/8529286 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: https://pubmed.ncbi.nlm.nih.gov/23993427 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: https://pubmed.ncbi.nlm.nih.gov/23993427 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: https://pubmed.ncbi.nlm.nih.gov/23993427 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: https://pubmed.ncbi.nlm.nih.gov/23993427 Page: p.6

Sourcing

Vendor/Aggregator	ID	URL
AChemBlock	10760	http://www.achemblock.com/catalogsearch/result/?q=10760
AK Scientific	2082AH	https://aksci.com/item_detail.php?cat=2082AH
AOBIOUS INC	AOB5912	http://aobious.com/aobious/search?search_query=AOB5912
Angene	AGN-PC-0RBFA3	http://www.angenechemical.com/productshow/AGN-PC-0RBFA3.html
ApexBio Technology	A8541	https://www.apexbt.com/catalogsearch/result/?q=A8541
AstaTech	C15666	http://astatechinc.com/CPSResult.php?CRNO=C15666
BOC Sciences	35943-35-2	http://www.bocsci.com/description.asp?cas=35943-35-2
BioSynth	W-202483	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/W-202483
Cayman Chemical	10010237	http://www.caymanchem.com/app/template/Product.vm/catalog/10010237
Chem Scene	CS-0968	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0968
ChemShuttle	109829	https://www.chemshuttle.com/catalogsearch/result/?q=109829
Debye Scientific	DB-048898	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-048898
Hairui	HR144084	http://www.hairuichem.com/en/product/search.do?q=HR144084
Lab Network	LN01315918	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01315918
Lab Seeker	SC-89664	http://www.labseeker.com/search.php?keywords=SC-89664&category=0
LabSeeker	SC-89664	http://www.labseeker.com/search.php?keywords=SC-89664&category=0
MedChem Express	HY-15457	https://www.medchemexpress.com/search.html?q=HY-15457&ft=&fa=&fp=
MolPort	MolPort-009-019-297	https://www.molport.com/shop/molecule-link/MolPort-009-019-297
MolPort	MolPort-021-805-017	https://www.molport.com/shop/molecule-link/MolPort-021-805-017
Molnova	M14234	https://www.molnova.com/en/serch-list.html?keywords=M14234
MuseChem	I003315	https://www.musechem.com/product/I003315.html
TargetMol	T6065	https://www.targetmol.com/search?keyword=T6065
Tetrahedron	TS61560	http://www.thsci.com/search.do?q=TS61560
Tocris	2151	https://www.tocris.com/search.php?Type=QuickSearch&Value=2151
Toronto Research Chemicals	T774245	https://www.trc-canada.com/product-detail/?CatNum=T774245
eMolecules	300081155	https://orderbb.emolecules.com/search/#?query=300081155
eMolecules	32234150	https://orderbb.emolecules.com/search/#?query=32234150
eMolecules	44811330	https://orderbb.emolecules.com/search/#?query=44811330
eMolecules	48874327	https://orderbb.emolecules.com/search/#?query=48874327
eMolecules	50580345	https://orderbb.emolecules.com/search/#?query=50580345
eNovation Chemicals	D372509	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D372509&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-1334932379	https://mcule.com/MCULE-1334932379/
mcule	MCULE-6539598127	https://mcule.com/MCULE-6539598127/

PubMed

Title	Date	PubMed
Activity of triciribine and triciribine-5'-monophosphate against human immunodeficiency virus types 1 and 2.	1993 Apr	7685612
Deoxy sugar analogues of triciribine: correlation of antiviral and antiproliferative activity with intracellular phosphorylation.	2000 Jun 15	10882371
1-Nitropyrene stabilizes the mRNA of cytochrome P450 1a1, a carcinogen-metabolizing enzyme, via the Akt pathway.	2009 Dec	19961161
High-throughput screening compatible cell-based assay for interrogating activated notch signaling.	2009 Feb	19382889
Inhibition of human immunodeficiency virus type 1 by triciribine involves the accessory protein nef.	2010 Apr	20086149
Preclinical testing of the Akt inhibitor triciribine in T-cell acute lymphoblastic leukemia.	2011 Mar	20857426
Ursodeoxycholic acid suppresses mitochondria-dependent programmed cell death induced by sodium nitroprusside in SH-SY5Y cells.	2012 Feb 26	22178905
Inhibitory roles of prohibitin and chemerin in FSH-induced rat granulosa cell steroidogenesis.	2013 Feb	23254195
Piceatannol suppresses the metastatic potential of MCF10A human breast epithelial cells harboring mutated H-ras by inhibiting MMP-2 expression.	2013 Oct	23877152
Insulin attenuates arsenic-induced neurite outgrowth impairments by activating the PI3K/Akt/SIRT1 signaling pathway.	2015 Aug 5	25982963

Patents

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.

Name

Type

Language

TRICIRIBINE PHOSPHATE

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