CRT0066101

Name: CRT0066101
Brand: Selleck Chemicals
SKU: S8366
Rating: 5 (0 reviews)

For research use only.

Catalog No.S8366

CAS No. 1883545-60-5

CRT0066101 is a small molecule PKD family specific inhibitor which specifically blocks PKD1/2 activity and does not suppress PKCα/PKCβ/PKCε activity in multiple.

Purity & Quality Control

Choose Selective PKD Inhibitors

Biological Activity

Description

CRT0066101 is a small molecule PKD family specific inhibitor which specifically blocks PKD1/2 activity and does not suppress PKCα/PKCβ/PKCε activity in multiple.

Targets

PKD1 ^[1] (Cell-free assay)	PKD3 ^[1] (Cell-free assay)	PKD2 ^[1] (Cell-free assay)
1 nM	2 nM	2.5 nM

In vitro

CRT0066101 reduces BrdU incorporation, increases apoptosis, blocks neurotensin (NT)-induced PKD1/2 activation, reduces NT-induced PKD-mediated Hsp27 phosphorylation, attenuates PKD1-mediated NF-κB activation, and abrogates expression of NF-κB-dependent-dependent proliferative and pro-survival proteins. CRT0066101 significantly inhibits Panc-1 cell proliferation with an IC50 value of 1 μM. It also significantly reduces cell proliferation of Colo357, Panc-1, MiaPaCa-2, and AsPC-1 cells but has a modest effect in Capan-2 cells. Thus, CRT0066101 significantly blocks proliferation of PaCa cells that express moderate to high endogenous levels of PKD1/2. CRT0066101 (5 µM) blocks both the basal and NT-induced pS916-PKD1/2 (activated PKD1/2) in Panc-1 and Panc-28 cells, also abrogates NT-induced phosphorylation of Hsp27 (pS82-Hsp27), which is a physiological substrate of PKD1/2 in a dose-dependent manner^[1].

Assay

Methods	Test Index	PMID
Western blot	Ppkd/PKC μ / pGSK3α / pGSK3β / β-catenin; PubMed: 26895471 Oncotarget Western blot analysis of GSK3/β-catenin signaling following treatment with 0.1–10 μM of CRT0066101 in MCF-7-ADR cell lines. Blots are representative of five independent experiments. β-actin was used as the loading control. p-AKT / AKT / p-ERK / ERK; PubMed: 24634417 Mol Cancer Ther Cells were exposed to CRT0066101 for 24 hours, and protein expression was determined by Western blot analysis. Cyclin D1 / Survivin / cIAP-1; PubMed: 20442301 Mol Cancer Ther Panc-1 cells were either transfected with control (Panc-1) or PKD1 over-expressing (Panc-1-PKD1) vectors and 23 h post-transfection were treated with DMSO (−) or 5 µM CRT0066101 (+) for 1 h prior to preparation of whole cell lysates to analyze effects on 䲧疝Ỵ疞㧀疜膉痘 瘿뾠ՂᾰƌՂĀ 㺣痖帉痖Ѐ瑖堘𢡄빢᎒ՂĀ鑸᎒彿堙奋堙巫堙᎒ﻺ᎒彿堙ﻮ᎒塚堙ﻺ᎒ꍈ堞빢᎒學堙漸堞圔堙빢᎒	26895471 24634417 20442301

In vivo

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. 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 (p< 0.01), increases TUNEL+ apoptotic cells (p<0.05), and abrogates expression of NF-κB-dependent proteins including cyclin D1, survivin, and cIAP-1. CRT0066101 blocks Panc-1 cell proliferation and growth in multiple xenograft models^[1]

Protocol

Cell Research:

^[1]

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Cell lines: Panc-1 cells
Concentrations: 5 μM
Incubation Time: 1 h
Method:
Panc-1 cells are either transfected with control (Panc-1) or PKD1 over-expressing (Panc-1-PKD1) vectors and 23 h post-transfection are treated with DMSO (−) or 5 µM CRT0066101 (+) for 1 h prior to preparation of nuclear extracts (NE) for measuring NF-κB activation by EMSA

(Only for Reference)

Animal Research:

^[1]

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Animal Models: CR-UK nu/nu mice
Dosages: 80 mg/kg
Administration: by oral gavage
(Only for Reference)

References

[1] Harikumar KB, et al. Mol Cancer Ther. 2010, 9(5):1136-46.

Solubility (25°C)

In vitro	Water	82 mg/mL (199.35 mM)
	DMSO	25 mg/mL warmed (60.77 mM)
	Ethanol	'''2 mg/mL warmed

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download CRT0066101 SDF

Molecular Weight	411.33
Formula	C₁₈H₂₂N₆O.2HCl
CAS No.	1883545-60-5
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CCC(CNC1=NC(=NC=C1)C2=C(C=CC(=C2)C3=CN(N=C3)C)O)N.Cl.Cl

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