CMPD 7 (also known as AZ1992) is a novel, highly potent and selective CDK12 inhibitor with an IC50 of 491 nM in an enzymatic assay. AZ1992 is a highly potent and selective CDK12 inhibitor with IC50 = 491 nM. AZ1992 showed 5-fold CDK2 and near 20-fold CDK9 selectivity. AZ1992 was profiled across a panel of 352 kinases at 0.1 mm followed by concentration–response testing in 30 of the top hits, showing that AZ1992 is a highly selective CDK12 inhibitor, and this result was confirmed by affinity proteomics using a kinase affinity matrix.

Physicochemical Properties

Molecular Formula	C23H28F2N8O
Molecular Weight	470.518230438232
Exact Mass	470.235
CAS #	2220184-50-7
Appearance	White to off-white solid powder
LogP	3.4
SMILES	FC1=C(C=CC2=C1N=C(CNC1C3=C(N(C=N3)C(C)C)N=C(N=1)N1CCCCC1CCO)N2)F
InChi Key	KULPPFCRBINTBS-AWEZNQCLSA-N
InChi Code	InChI=1S/C23H28F2N8O/c1-13(2)33-12-27-20-21(26-11-17-28-16-7-6-15(24)18(25)19(16)29-17)30-23(31-22(20)33)32-9-4-3-5-14(32)8-10-34/h6-7,12-14,34H,3-5,8-11H2,1-2H3,(H,28,29)(H,26,30,31)/t14-/m0/s1
Chemical Name	(S)-2-(1-(6-(((6,7-Difluoro-1H-benzo[d]imidazol-2-yl)methyl)amino)-9-isopropyl-9H-purin-2-yl)piperidin-2-yl)ethan-1-ol
Synonyms	CMPD7;CMPD 7; CMPD-7; AZ1992; AZ-1992; AZ 1992; Compound 7
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	CDK12-IN-3 is a CDK12 reagent that is very sensitive. Strong suppression of Ser2 phosphorylation on RNA Pol II's CTD repeat domain, together with OV90 cell growth inhibition and THP1 cell acute cytotoxicity, are demonstrated by CDK12-IN-3 (0.1 μM) [1].
References	[1]. Structure-Based Design of Selective Noncovalent CDK12 Inhibitors. ChemMedChem. 2018 Feb 6;13(3):231-235.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~531.33 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.33 mg/mL (4.95 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 23.3 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: ≥ 2.33 mg/mL (4.95 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 23.3 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	2.1253 mL	10.6265 mL	21.2531 mL
	5 mM	0.4251 mL	2.1253 mL	4.2506 mL
	10 mM	0.2125 mL	1.0627 mL	2.1253 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.