CPI-203 (RO6870810, JQ-2, TEN010, RG6146) is a novel, selective, cell permeable and orally bioavailable BET bromodomain inhibitor with anticancer activity. It inhibits BRD4 with an IC50 of 37 nM in a BRD4 α-screen assay. CPI 203 shows potent in vitro antiproliferative activity and high in vivo antitumor efficacy. CPI203 can enhance the antiproliferative effects of rapamycin on human neuroendocrine tumors. CPI203 can downregulate Myc expression, causes G1 cell cycle arrest and attenuate cell proliferation in human pancreatic neuroendocrine tumors. CPI203 arrests the growth of T cell acute lymphoblastic leukemia cells in vitro (EC50 = 91.2 nM).

Physicochemical Properties

Molecular Formula	C19H18CLN5OS
Molecular Weight	399.90
Exact Mass	399.092
CAS #	1446144-04-2
Related CAS #	(Rac)-CPI-203;202591-23-9
PubChem CID	71291068
Appearance	Light yellow to yellow solid powder
Density	1.5±0.1 g/cm3
Boiling Point	690.5±65.0 °C at 760 mmHg
Flash Point	371.4±34.3 °C
Vapour Pressure	0.0±2.2 mmHg at 25°C
Index of Refraction	1.749
LogP	1.85
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	3
Heavy Atom Count	27
Complexity	611
Defined Atom Stereocenter Count	1
SMILES	CC1=C(SC2=C1C(=N[C@H](C3=NN=C(N32)C)CC(=O)N)C4=CC=C(C=C4)Cl)C
InChi Key	QECMENZMDBOLDR-AWEZNQCLSA-N
InChi Code	InChI=1S/C19H18ClN5OS/c1-9-10(2)27-19-16(9)17(12-4-6-13(20)7-5-12)22-14(8-15(21)26)18-24-23-11(3)25(18)19/h4-7,14H,8H2,1-3H3,(H2,21,26)/t14-/m0/s1
Chemical Name	2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetamide
Synonyms	RO-6870810;CPI203; CPI-203; CPI 203;RO 6870810; TEN010;RG 6146; RG-6146;TEN 010; TEN010; JQ-2; JQ 2; JQ2; RG-6146; RO6870810;
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

ln Vitro	CPI-203 inhibits BRD4 in vitro and in cells, but does not influence BRD4 kinase activity in vitro [1]. CPI -203 had cytostatic effects in all 9 MCL cell lines with GI50 ranging from 0.06 to 0.71 μM and had little cytotoxicity against normal PBMC from healthy volunteers. In addition, CPI -203 can effectively initiate the cell death pathway in MCL cells [2].
ln Vivo	Lenalidomide and CPI-203 (2.5 mg/kg, i.p.) together improved the anticancer effects of each individual drug by causing apoptosis in nREC-1 tumor-bearing mice and mutating MYC and IRF4 expression. [2].
Animal Protocol	2.5 mg/kg i.p. Treatment with JQ1 derivative CPI203 inhibits BRD4 phosphorylation of CTD Ser2 in vivo. HeLa cells were transfected as above and treated with increasing concentrations of CPI203.
References	[1]. BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain. Proc Natl Acad Sci U S A. 2012 May 1;109(18):6927-32. [2]. Synergistic antitumor activity of lenalidomide with the BET bromodomain inhibitor CPI203 in bortezomib-resistant mantle cell lymphoma. Leukemia. 2014 Oct;28(10):2049-59.

Solubility Data

Solubility (In Vitro)

DMSO: 79 mg/mL (197.54mM) Water:<1 mg/mL Ethanol: 5 mg/mL (12.5 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.25 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (6.25 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.25 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5006 mL	12.5031 mL	25.0063 mL
	5 mM	0.5001 mL	2.5006 mL	5.0013 mL
	10 mM	0.2501 mL	1.2503 mL	2.5006 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.