BRICICLIB SODIUM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H21O10PS.2Na
Molecular Weight	518.382
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].[Na+].COC1=CC(OC)=C(\C=C\S(=O)(=O)CC2=CC(OP([O-])([O-])=O)=C(OC)C=C2)C(OC)=C1

InChI

InChIKey=MIBWXNAYNGADJD-MIIBGCIDSA-L

InChI=1S/C19H23O10PS.2Na/c1-25-14-10-17(27-3)15(18(11-14)28-4)7-8-31(23,24)12-13-5-6-16(26-2)19(9-13)29-30(20,21)22;;/h5-11H,12H2,1-4H3,(H2,20,21,22);;/q;2*+1/p-2/b8-7+;;

HIDE SMILES / InChI

Description
Sources: https://clinicaltrials.gov/ct2/show/NCT02168725 | https://clinicaltrials.gov/ct2/show/NCT01049113 | https://www.onconova.com/pipeline/#tab-id-3

Briciclib (also known as ON-013105 and ON-014185) has the potential of targeting and inhibition of eukaryotic translation initiation factor 4E (eIF4E) for solid cancers. eIF4E is a proto-oncogene that promotes translation of several genes essential for cellular proliferation (cyclin D1, c-Myc, mTOR), survival (Akt), angiogenesis (VEGF), and metastasis (MMP9). Overexpression of eIF4E has been observed in almost all major groups of cancers and has been shown to induce increased expression of cyclin D1 and c-Myc). An intravenous formulation of briciclib was being investigated in the Phase 1 clinical trial. The purpose of the study was to determine the highest dose of briciclib that could be given safely in patients with relapsed/refractory Lymphoma or B-cell Acute Lymphocytic Leukemia (Philadelphia chromosome negative). However, this study was terminated because of the lack of available clinical drug supply. In addition, briciclib was also involved in phase I clinical trials with advanced cancer and solid tumors, to determine the highest dose that can be safely given.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Eukaryotic translation initation factor 3 Target ID: CHEMBL4848 Sources: http://cancerres.aacrjournals.org/content/75/15_Supplement/1649	Inhibitor 8297

PubMed

Title	Date	PubMed
Combined administration of rituximab and on 013105 induces apoptosis in mantle cell lymphoma cells and reduces tumor burden in a mouse model of mantle cell lymphoma.	2013 Jan 1	23124440

Patents

Sample Use Guides

In Vivo Use Guide

The starting dose of briciclib in the Escalation Stage will be 17 mg/week, with subsequent dose escalation levels of 35 mg, 70 mg, 140 mg, 280 mg, 560 mg, and 1120 mg. At each dose level, briciclib will be administered as a 2-hour intravenous infusion, once-a-week per 3-week cycles.

Route of Administration: Intravenous

Name

Type

Language

BRICICLIB SODIUM

Official Name

English

BRICICLIB SODIUM [USAN]

Common Name

English

Briciclib sodium [WHO-DD]

Common Name

English

PHENOL, 2-METHOXY-5-((((1E)-2-(2,4,6-TRIMETHOXYPHENYL)ETHENYL)SULFONYL)METHYL)-, 1-(DIHYDROGEN PHOSPHATE), SODIUM SALT (1:2)

Common Name

English

(E)-5-(((2,4,6-TRIMETHOXYSTYRYL)SULFONYL)METHYL)-2-METHOXYPHENYL DIHYDROGEN PHOSPHATE DISODIUM SALT

Common Name

English

2-Methoxy-5-({[2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonyl}methyl)phenyl disodium phosphate

Systematic Name

English

ON013105

Code

English

ON-013105

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C129825