CDK12-IN-5, a pyrazotriazine, is a potent CDK12 inhibitor (antagonist) with IC50 of 23.9 nM at high ATP (2 mM). CDK12-IN-5 has no effect on CDK2/Cyclin E (IC50=173 μM) and CDK9/Cyclin T1 (IC50=127 μM) under high ATP (2 mM) (WO2021116178A1).

Physicochemical Properties

Molecular Formula	C18H15F5N8O
Molecular Weight	454.356719255447
Exact Mass	454.128
CAS #	2651200-35-8
PubChem CID	156482226
Appearance	White to off-white solid powder
LogP	2.7
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	12
Rotatable Bond Count	4
Heavy Atom Count	32
Complexity	655
Defined Atom Stereocenter Count	0
SMILES	N12N=CC(C(F)(F)F)=C1N=C(N1CCOCC1)N=C2NCC1NC2=C(F)C(F)=CC=C2N=1
InChi Key	XFZQHKMIWRKKCU-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H15F5N8O/c19-10-1-2-11-14(13(10)20)27-12(26-11)8-24-16-29-17(30-3-5-32-6-4-30)28-15-9(18(21,22)23)7-25-31(15)16/h1-2,7H,3-6,8H2,(H,26,27)(H,24,28,29)
Chemical Name	N-[(4,5-difluoro-1H-benzimidazol-2-yl)methyl]-2-morpholin-4-yl-8-(trifluoromethyl)pyrazolo[1,5-a][1,3,5]triazin-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
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	CDK12 23.9 nM (IC50) CDK2/cyclinE 173 μM (IC50) CDK9/cyclinT1 127 μM (IC50)
ln Vitro	In MDA-MB-231 cells, CDK12-IN-5 (Example 426) suppresses BRCA1 MRNA expression (IC50=3.23 nM), while having no effect on CAL-120 cells[1]. With MDA-MB-231 cells (IC50=4.19 nM) and CAL-120 cells (IC50=3.57 nM), CDK12-IN-5 exhibits antiproliferative activity[1]. The IC50 CDK12 high ATP to Degradation DC50 CDK12 ratio of CDK12-IN-5 is 32[1].
References	[1]. Pyrazolotriazines. WO2021116178A1.

Solubility Data

Solubility (In Vitro)

DMSO : 125 mg/mL (275.11 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.08 mg/mL (4.58 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (4.58 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 20.8 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	2.2009 mL	11.0045 mL	22.0090 mL
	5 mM	0.4402 mL	2.2009 mL	4.4018 mL
	10 mM	0.2201 mL	1.1004 mL	2.2009 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.