CPI-637 is a novel, potent, selective and cell-bioactive benzodiazepinone analog that acts as a CBP/EP300 bromodomain inhibitor with IC50 of 0.03±0.01μM and 11.0±0.6 μM for CBP/EP300 and BRD4, respectively. CPI-637, which demonstrated substantial biochemical potency that was confirmed by isothermal titration calorimetry. A cocrystal structure of CPI-637 in the CBP bromodomain indicated that the compound recapitulated the key hydrogen bonding interactions observed with the parent compound, with the substituted indazole filling space above Pro1110 and the Pro/Arg cleft . As expected, CPI-637 was also potent against EP300, and its opposite enantiomer displayed a >200-fold loss in potency.

Physicochemical Properties

Molecular Formula	C22H22N6O
Molecular Weight	386.45
Exact Mass	386.185
Elemental Analysis	C, 68.38; H, 5.74; N, 21.75; O, 4.14
CAS #	1884712-47-3
Related CAS #	1884712-47-3
PubChem CID	121271792
Appearance	White to off-white solid powder
Density	1.4±0.1 g/cm3
Boiling Point	689.2±55.0 °C at 760 mmHg
Flash Point	370.6±31.5 °C
Vapour Pressure	0.0±2.2 mmHg at 25°C
Index of Refraction	1.732
LogP	2.77
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	29
Complexity	616
Defined Atom Stereocenter Count	1
SMILES	O=C1C([H])([H])[C@@]([H])(C([H])([H])[H])N([H])C2C(=C([H])C([H])=C([H])C=2C2C([H])=C([H])C3=C(C(C4C([H])=NN(C([H])([H])[H])C=4[H])=NN3C([H])([H])[H])C=2[H])N1[H]
InChi Key	BFTKDWYIRJGJCA-CYBMUJFWSA-N
InChi Code	InChI=1S/C22H22N6O/c1-13-9-20(29)25-18-6-4-5-16(22(18)24-13)14-7-8-19-17(10-14)21(26-28(19)3)15-11-23-27(2)12-15/h4-8,10-13,24H,9H2,1-3H3,(H,25,29)/t13-/m1/s1
Chemical Name	(4R)-4-methyl-6-[1-methyl-3-(1-methylpyrazol-4-yl)indazol-5-yl]-1,3,4,5-tetrahydro-1,5-benzodiazepin-2-one
Synonyms	CPI-637; CPI 637; CPI637
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	In AMO-1 cells, CPI-637 (Compound 28) suppresses MYC expression (EC50 value: 0.60 μM)[1].
ln Vivo
Animal Protocol
References	[1]. Fragment-Based Discovery of a Selective and Cell-Active Benzodiazepinone CBP/EP300 Bromodomain Inhibitor (CPI-637). ACS Med Chem Lett. 2016 Mar 15;7(5):531-6.

Solubility Data

Solubility (In Vitro)

DMSO:27 mg/mL (69.9 mM) Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 0.96 mg/mL (2.48 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 9.6 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: 0.96 mg/mL (2.48 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 9.6 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: ≥ 0.96 mg/mL (2.48 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 9.6 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	2.5877 mL	12.9383 mL	25.8766 mL
	5 mM	0.5175 mL	2.5877 mL	5.1753 mL
	10 mM	0.2588 mL	1.2938 mL	2.5877 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.