CF53 is a highly efficient, selective, orally bioavailable BET inhibitor (antagonist) with Ki of <1 nM, Kd of 2.2 nM, and IC50 of 2 nM for BRD4 BD1; CF53 is effective against BRD2, BRD3, BRD4 and BRDT BET proteins. Both domains of BD1 and BD2 have high affinity, and their selectivity is much higher than that of non-bromodomain-containing BET proteins. CF53 displays significant anti-tumor effects both in vitro & in vivo.

Physicochemical Properties

Molecular Formula	C24H25N7O2
Molecular Weight	443.501003980637
Exact Mass	443.206
CAS #	1808160-52-2
Related CAS #	1808160-52-2;1808162-97-1 (TFA);
PubChem CID	118340554
Appearance	Light yellow to yellow solid powder
LogP	4.3
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	5
Heavy Atom Count	33
Complexity	710
Defined Atom Stereocenter Count	0
SMILES	O(C)C1C(C2C(C)=NOC=2C)=CC2=C(C=1)C1C(=NC(C)=NC=1NC1=CC(C3CC3)=NN1C)N2
InChi Key	JIYPVUCBRQNICX-UHFFFAOYSA-N
InChi Code	InChI=1S/C24H25N7O2/c1-11-21(12(2)33-30-11)16-8-18-15(9-19(16)32-5)22-23(27-18)25-13(3)26-24(22)28-20-10-17(14-6-7-14)29-31(20)4/h8-10,14H,6-7H2,1-5H3,(H2,25,26,27,28)
Chemical Name	N-(5-cyclopropyl-2-methylpyrazol-3-yl)-7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-amine
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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
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	CF53 (compound 28) exhibits significant affinity for the BD1 and BD2 domains of BRD2, BRD3, BRD4, and BRDT BET proteins. Kds for these domains are 0.49, 0.6, and 0.52 nM, respectively, for BRD2 BD1, BRD2 BD2, and BRD3 BD1. 47 nM (CREBBP), 570 nM (CECR2), 110 nM (EP300), 2 nM (BRDT BD1), 2.1 nM (BRDT BD2), 0.8 nM (BRD4 BD2), and nM (BRD3 BD2)[1]. The MOLM-13 acute leukemia and MDA-MB-231 breast cancer cell lines have IC50 values of 7 and 85 nM, respectively, for CF53[1].
ln Vivo	CF53 (25, 50 mg/kg, orally) has strong anticancer efficacy in the mouse RS4;11 model and the MDA-MB-231 xenograft tumor model [1].
References	[1]. Structure-Based Discovery of CF53 as a Potent and Orally Bioavailable Bromodomain and Extra-Terminal (BET) Bromodomain Inhibitor. J Med Chem. 2018 Jul 26;61(14):6110-6120.

Solubility Data

Solubility (In Vitro)

DMSO : ~110 mg/mL (~248.03 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.83 mg/mL (4.13 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 18.3 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: ≥ 1.83 mg/mL (4.13 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 18.3 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	2.2548 mL	11.2740 mL	22.5479 mL
	5 mM	0.4510 mL	2.2548 mL	4.5096 mL
	10 mM	0.2255 mL	1.1274 mL	2.2548 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.