CRT0066101 is a potent and orally active PKD inhibitor with IC50 values of 1 nM, 2.5 nM and 2 nM for PKD1, PKD2 and PKD3, respectively. CRT0066101 is also a potent PIM2 inhibitor with IC50 of approximately 135.7 nM. CRT0066101 has anticancer effects.

Physicochemical Properties

Molecular Formula	C18H22N6O
Molecular Weight	338.41
Exact Mass	374.162
CAS #	956123-34-5
PubChem CID	136189563
Appearance	Solid powder
LogP	2.522
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	6
Heavy Atom Count	25
Complexity	411
Defined Atom Stereocenter Count	1
SMILES	Cl.OC1=CC=C(C2C=NN(C)C=2)C=C1C1=NC=CC(=N1)NC[C@@H](CC)N
InChi Key	SCJXQZZYGYLKJG-CQSZACIVSA-N
InChi Code	InChI=1S/C18H22N6O/c1-3-14(19)10-21-17-6-7-20-18(23-17)15-8-12(4-5-16(15)25)13-9-22-24(2)11-13/h4-9,11,14,25H,3,10,19H2,1-2H3,(H,20,21,23)/t14-/m1/s1
Chemical Name	2-[4-[[(2R)-2-aminobutyl]amino]pyrimidin-2-yl]-4-(1-methylpyrazol-4-yl)phenol
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	PKD1 1 nM (IC50) PKD2 2.5 nM (IC50) PKD3 2 nM (IC50) PIM2 135.7 nM (IC50)
ln Vitro	CRT0066101 (5 µM; 1 h) blocks basal and NT-induced pS916-PKD1/2 (activated PKD1/2) in Panc-1 and Panc-28 cells. CRT0066101 abolishes NT-induced Hsp27 (pS82-Hsp27) phosphorylation, attenuates PKD1-mediated NF-κB activation, and eliminates the expression of NF-κB-dependent proliferative and pro-survival proteins[1]. CRT0066101 significantly inhibits Panc-1 cell proliferation with an IC50 value of 1 µM. CRT0066101 induces apoptosis of Panc-1 cells 6-10-fold. CRT0066101 significantly reduces the proliferation of Colo357, Panc-1, MiaPaCa-2, and AsPC-1 cells, but has some effects on Capan-2 cells[1].
ln Vivo	CRT0066101 (80 mg/kg/day; oral gavage; once daily; for 21 days) effectively blocked tumor growth in vivo in the Panc-1 orthotopic model [1].
Cell Assay	Western Blot Analysis[1] Cell Types: Panc-1 and Panc-28 cells stimulation with neurotensin (NT) Concentration: 5 µM Incubation Duration: 1 h Experimental Results: Blocked both the basal and NT-induced pS916-PKD1/2 (activated PKD1/2).
Animal Protocol	Animal/Disease Models:CR-UK nu/nu mice injected with Panc-1 cells[1] Doses: 80 mg/kg/day Route of Administration: Oral gavage; once daily; for 21 days Experimental Results: Potently blocked tumor growth in vivo.
References	[1]. A novel small-molecule inhibitor of protein kinase D blocks pancreatic cancer growth in vitro and in vivo. Mol Cancer Ther. 2010 May;9(5):1136-46. [2]. Identification and assessment of new PIM2 inhibitors for treating hematologic cancers: A combined approach of energy-based virtual screening and machine learning evaluation. Arch Pharm (Weinheim). 2024 Jan 23:e2300516.

Solubility Data

Solubility (In Vitro)

DMSO : 100 mg/mL (295.50 mM; with sonication)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.39 mM)(Saturation unknown) in 10% DMSO 40% PEG300 5% Tween-80 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, add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix well; then add 50 μL Tween-80 to the above system and mix well; then add 450 μL saline to make it 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 (7.39 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, add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD in saline and mix well. *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 (7.39 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, add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL corn oil and mix well.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.9550 mL	14.7750 mL	29.5500 mL
	5 mM	0.5910 mL	2.9550 mL	5.9100 mL
	10 mM	0.2955 mL	1.4775 mL	2.9550 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.