CRT0066101 dihydrochloride

CRT0066101 dihydrochloride is a potent and specific PKD inhibitor with IC50 values of 1, 2.5 and 2 nM for PKD1, 2, and 3 respectively.

Product information

CAS Number: 1883545-60-5

Molecular Weight: 411.33

Formula: C18H24Cl2N6O

Chemical Name: 2-(4-{[(2R)-2-aminobutyl]amino}pyrimidin-2-yl)-4-(1-methyl-1H-pyrazol-4-yl)phenol dihydrochloride

Smiles: Cl.Cl.CC[C@@H](N)CNC1=CC=NC(=N1)C1=CC(=CC=C1O)C1=CN(C)N=C1

InChiKey: CXYCRYGNFKDPRH-FMOMHUKBSA-N

InChi: InChI=1S/C18H22N6O.2ClH/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);2*1H/t14-;;/m1../s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: H2O : 50 mg/mL (121.56 mM; Need ultrasonic) DMSO : ≥ 25 mg/mL (60.78 mM)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

CRT0066101 specifically blocks PKD1/2 activity and does not suppress PKCα/PKCβ/PKCε activity in multiple cancer cell types including A549 (lung) and MiaPaCa-2 (pancreas). CRT0066101 significantly inhibits Panc-1 cell proliferation with an IC50 value of 1 µM. Treatment with CRT0066101 results in a 6-10 fold induction of apoptosis in Panc-1 cells. CRT0066101 significantly reduces cell proliferation of Colo357, Panc-1, MiaPaCa-2, and AsPC-1 cells but has a modest effect in Capan-2 cells. CRT0066101 (5 µM) blocks both the basal and NT-induced pS916-PKD1/2 (activated PKD1/2) in Panc-1 and Panc-28 cells. CRT0066101 reduces PKD-dependent NF-κB activation and NF-κB-dependent gene expressions in Panc-1.

In Vivo:

Optimal therapeutic concentrations (8 µM) of CRT0066101 are detectable 6 h after oral administration of this drug. CRT0066101 given orally (80 mg/kg/day) for 28 days significantly abrogates PaCa growth in Panc-1 subcutaneous xenograft model. Activated PKD1/2 expression in the treated tumor-explants is significantly inhibited with peak tumor concentration (12 µM) of CRT0066101 achieved within 2 h after oral administration. Further, CRT0066101 given orally (80 mg/kg/day) for 21 days in Panc-1 orthotopic model potently blocks tumor growth in vivo. CRT0066101 significantly reduces Ki-67+ proliferation index, increases TUNEL+ apoptotic cells (p<0.05), and abrogates expression of NF-κB-dependent proteins including cyclin D1, survivin, and cIAP-1.

References:

1. Harikumar KB, et al. 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.

Products are for research use only. Not for human use.