CRT0066101 . HCl
| Code | Size | Price |
|---|
| AG-CR1-3550-M001 | 1 mg | £50.00 |
Quantity:
Prices exclude any Taxes / VAT
Overview
Regulatory Status: RUO
Shipping:
AMBIENT
Storage:
Short term storage:+4°C. Long term storage:-20°C.
Documents
Further Information
Alternate Names/Synonyms:
2-[4-[[(2R)-2-Aminobutyl]amino]-2-pyrimidinyl]-4-(1-methyl-1H-pyrazol-4-yl)-phenol . hydrochloride
Appearance:
White to off-white solid.
CAS:
1781742-22-0
EClass:
32160000
Form (Short):
solid
GHS Symbol:
GHS07
Handling Advice:
Protect from light when in solution.
Hazards:
H302
InChi:
InChI=1S/C18H22N6O.3ClH/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);3*1H/t14-;;;/m1../s1
InChiKey:
HWZPJKPBOZVLEB-XJCLVHIMSA-N
Long Description:
Chemical. CAS: 1781742-22-0. Formula: C18H22N6O . 3HCl. MW: 338.4 . 109.4. CRT0066101 is an inhibitor of all three PKD isoforms (IC50s = 1, 2.5, and 2 nM for PKD1, PKD2 and PKD3, respectively). It exhibits selectivity for PKD against a panel of >90 protein kinases, including PKCalpha, PKBalpha, MEK, ERK, c-Raf, c-Src and c-Abl. PKD family members play an important role in regulating several cellular processes and activities, including chromatin organization, Golgi function, gene expression, cell survival, adhesion, motility, differentiation, DNA synthesis and proliferation. CRT0066101 shows anticancer activity by blocking cell proliferation, inducing apoptosis, G2/M phase arrest, inhibiting migration and invasion and reducing the viability of several cancer cells both in vitro and in vivo. CRT0066101 reduced PKD-dependent NF-kappaB activation and NF-kappaB-dependent gene expressions in pancreatic cancer cells in vitro and showed antiviral activities inhibiting viral RNA replication and viral protein expression. Protein kinase D (PKD) has emerged as an important NLRP3 kinase that catalyzes the release of a phosphorylated NLRP3 species that is competent for inflammasome complex assembly. PKD inhibitor CRT0066101 could block NLRP3 inflammasome assembly and interleukin-1beta production. CRT0066101 also inhibits MyD88 and TLR4 expression and reduces NF-kappaB, ERK and JNK phosphorylation, indicating that it exerts anti-inflammatory effects on LPS-induced inflammation through the TLR4/MyD88 signaling pathway.
MDL:
MFCD28044320
Molecular Formula:
C18H22N6O . 3HCl
Molecular Weight:
338.4 . 109.4
Package Type:
Vial
Precautions:
P301, P312
Product Description:
CRT0066101 is an inhibitor of all three PKD isoforms (IC50s = 1, 2.5, and 2 nM for PKD1, PKD2 and PKD3, respectively). It exhibits selectivity for PKD against a panel of >90 protein kinases, including PKCalpha, PKBalpha, MEK, ERK, c-Raf, c-Src and c-Abl. PKD family members play an important role in regulating several cellular processes and activities, including chromatin organization, Golgi function, gene expression, cell survival, adhesion, motility, differentiation, DNA synthesis and proliferation. CRT0066101 shows anticancer activity by blocking cell proliferation, inducing apoptosis, G2/M phase arrest, inhibiting migration and invasion and reducing the viability of several cancer cells both in vitro and in vivo. CRT0066101 reduced PKD-dependent NF-kappaB activation and NF-kappaB-dependent gene expressions in pancreatic cancer cells in vitro and showed antiviral activities inhibiting viral RNA replication and viral protein expression. Protein kinase D (PKD) has emerged as an important NLRP3 kinase that catalyzes the release of a phosphorylated NLRP3 species that is competent for inflammasome complex assembly. PKD inhibitor CRT0066101 could block NLRP3 inflammasome assembly and interleukin-1beta production. CRT0066101 also inhibits MyD88 and TLR4 expression and reduces NF-kappaB, ERK and JNK phosphorylation, indicating that it exerts anti-inflammatory effects on LPS-induced inflammation through the TLR4/MyD88 signaling pathway.
Purity:
>98%
Signal word:
Warning
SMILES:
N[C@@H](CN([H])C1=CC=NC(C2=C(C=CC(C3=CN(N=C3)C)=C2)O)=N1)CC.Cl.Cl.Cl
Solubility Chemicals:
Soluble in water (10mg/ml) or DMSO (3mg/ml).
Transportation:
Non-hazardous
UNSPSC Number:
12352200
Use & Stability:
Stable for at least 2 years after receipt when stored at -20°C.
References
A novel small-molecule inhibitor of protein kinase D blocks pancreatic cancer growth in vitro and in vivo: K.B. Harikumar, et al.; Mol. Cancer Ther. 9, 1136 (2010) | Protein kinase D1 promotes anchorage-independent growth, invasion, and angiogenesis by human pancreatic cancer cells: N. Ochi, et al.; J. Cell Physiol. 226, 1074 (2011) | Protein kinase d regulates cell death pathways in experimental pancreatitis: J. Yuan, et al.; Front. Physiol. 3, 60 (2012) | Protein kinase d as a potential chemotherapeutic target for colorectal cancer: N. Wei, et al.; Mol. Cancer Ther. 13, 1130 (2014) | Effective Targeting of Estrogen Receptor-Negative Breast Cancers with the Protein Kinase D Inhibitor CRT0066101: S. Borges, et al.; Mol. Cancer Ther. 14, 1306 (2015) | Novel Small Molecule Inhibitors of Protein Kinase D Suppress NF-kappaB Activation and Attenuate the Severity of Rat Cerulein Pancreatitis: J. Yuan, et al.; Front. Physiol. 8, 1014 (2017) | Investigation of the Role of Protein Kinase D in Human Rhinovirus Replication: A. Guedan, et al.; J. Virol. 91, e00217 (2017) | Protein kinase D at the Golgi controls NLRP3 inflammasome activation: Z. Zhang, et al.; J. Exp. Med. 214, 2671 (2017) | Developments in the Discovery and Design of Protein Kinase D Inhibitors: P. Gilles, et al.; ChemMedChem 16, 2158 (2021) (Review) | Evaluation of protein kinase D auto-phosphorylation as biomarker for NLRP3 inflammasome activation: D. Heiser, et al.; PLoS One 16, e0248668 (2021) | Small molecule inhibitor CRT0066101 inhibits cytokine storm syndrome in a mouse model of lung injury: B. Cui, et al.; Int. Immunopharmacol. 120, 110240 (2023)