ON-013100 is a novel and potent inhibitor of cell cycle with the potential for the treatment of mantle cell lymphoma. Briciclib, also referred to as ON 013105 or ON 014185, is the prodrug of ON-013100 that is a disodium phosphate ester and is an orally bioavailable small molecule that has better water solubility than ON 013100. It is a derivative of benzyl styryl sulfone, which may have anticancer properties and suppress the build-up of cyclin D1 in cancer cells. Briciclib binds to eIF4E, preventing the cap-dependent translation of cyclin D1 and other cancer proteins (c-MYC, VEGF), which results in the death of tumor cells, according to in vitro data. In nonclinical tumor models, briciclib has demonstrated potency and activity when paired with multiple chemotherapeutics. In conclusion, data from both in vitro and in vivo studies show that briciclib has the potential to target eIF4E in solid and hematopoietic cancers, and that an oral form of this exciting therapeutic agent may be developed.

Physicochemical Properties

Molecular Formula	C19H22O7S
Molecular Weight	394.44
Exact Mass	394.109
Elemental Analysis	C, 57.86; H, 5.62; O, 28.39; S, 8.13
CAS #	865783-95-5
Related CAS #	Briciclib;865783-99-9
PubChem CID	11269418
Appearance	White to off-white solid powder
LogP	4.093
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	8
Heavy Atom Count	27
Complexity	557
Defined Atom Stereocenter Count	0
SMILES	C(/C1C(OC)=CC(OC)=CC=1OC)=C\S(=O)(=O)CC1C=CC(OC)=C(O)C=1
InChi Key	GHPUSRLWNSTQIK-BQYQJAHWSA-N
InChi Code	InChI=1S/C19H22O7S/c1-23-14-10-18(25-3)15(19(11-14)26-4)7-8-27(21,22)12-13-5-6-17(24-2)16(20)9-13/h5-11,20H,12H2,1-4H3/b8-7+
Chemical Name	2-methoxy-5-[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonylmethyl]phenol
Synonyms	ON 013100; ON-013100; ON013100
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Cdk4/cyclin D1
ln Vitro	ON-013100 has action against the majority of human cancer cell lines in vitro and induces apoptosis. By drastically increasing the number of cells in the G2/M phase, ON013100 dramatically modifies the cell cycle profile. When cells are treated with even 0.1 μM of ON013100, the G2/M phase of the cell cycle is arrested[2]. For MCL (JEKO-1 and MINO), breast (MCF7 and MDA-MB-231), gastric (AGS), and esophageal (OE19, OE33, and FLO-1) cancer cell lines, ON 013100 exhibits a nanomolar concentration (GI50=6.7-11.2 nM) that inhibits the proliferation of these cell lines [3].
ln Vivo
Animal Protocol
References	[1]. Determination of the glucuronide metabolite of ON 013100, a benzylstyrylsulfone antineoplastic drug, in colon cancer cells using LC/MS/MS. J Pharm Biomed Anal. 2013 Mar 5;75:138-44. [2]. Evaluation of novel cell cycle inhibitors in mantle cell lymphoma. Oncogene. 2007 Aug 16;26(38):5635-42. [3]. Potent anticancer activity of an orally bioavailable small molecule, ON 013100, and its water soluble derivative, briciclib, a clinical-stage eIF4E-targeted agent. AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA.

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 31 mg/mL Water: N/A Ethanol: N/A

Solubility (In Vivo)

Solubility in Formulation 1: 1.25 mg/mL (3.17 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 1.25 mg/mL (3.17 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5352 mL	12.6762 mL	25.3524 mL
	5 mM	0.5070 mL	2.5352 mL	5.0705 mL
	10 mM	0.2535 mL	1.2676 mL	2.5352 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.