Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C30H28O8 |
| Molecular Weight | 516.5385 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(=O)C1=C(O)C(CC2=C(O)C3=C(OC(C)(C)C=C3)C(C(=O)\C=C\C4=CC=CC=C4)=C2O)=C(O)C(C)=C1O
InChI
InChIKey=DEZFNHCVIZBHBI-ZHACJKMWSA-N
InChI=1S/C30H28O8/c1-15-24(33)19(27(36)22(16(2)31)25(15)34)14-20-26(35)18-12-13-30(3,4)38-29(18)23(28(20)37)21(32)11-10-17-8-6-5-7-9-17/h5-13,33-37H,14H2,1-4H3/b11-10+
Rottlerin is a principal phenolic compound of the Kamala plant Mallotus philippinensis. It was thought to be a selective inhibitor of PKCδ (protein kinase Cδ) (IC50=3-6 uM). It also inhibits PKCα, PKCβ, PKCγ, PKCε, PKCη, PKCζ and eEF2K (CaMK III) (IC50 = 5.3 uM). In HT1080 human fibrosarcoma cells, rottlerin induces apoptosis and autophagy via a PKCδ-independent pathway. When tested on HERG channels, rottlerin increased both step and tail HERG current by leftward shifting the voltage and dependence of HERG activation and slowing channel deactivation. Rottlerin is an inhibitor of Chk2, MAPKAPK-2, Pim-3, PKCλ, PKCθ, Plk, PRAK, SRPK1 and an activator of AMPK and HERG. There have been a number of studies published with evidence against the role of Rotterlin as a specific PKCδ inhibitor.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: Q12809|||Q9BUT7 Gene ID: 3757.0 Gene Symbol: KCNH2 Target Organism: Homo sapiens (Human) |
0.34 µM [EC50] | ||
Target ID: CHEMBL2996 |
3.0 µM [IC50] | ||
Target ID: CHEMBL3094 |
1.9 µM [IC50] | ||
Target ID: CHEMBL2208 |
5.4 µM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Protein kinase Cδ mediates trimethyltin-induced neurotoxicity in mice in vivo via inhibition of glutathione defense mechanism. | 2016-04 |
|
| A HAMP promoter bioassay system for identifying chemical compounds that modulate hepcidin expression. | 2015-05 |
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| Naringin protects against anoxia/reoxygenation-induced apoptosis in H9c2 cells via the Nrf2 signaling pathway. | 2015-04 |
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| Isorhamnetin protects against oxidative stress by activating Nrf2 and inducing the expression of its target genes. | 2014-01-15 |
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| PKCδ mediates paraquat-induced Nox1 expression in dopaminergic neurons. | 2013-08-02 |
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| Rottlerin induces autophagy which leads to apoptotic cell death through inhibition of PI3K/Akt/mTOR pathway in human pancreatic cancer stem cells. | 2012-11-01 |
|
| Phorbol ester-modulation of estrogenic genomic effects triggered by the environmental contaminant benzanthracene. | 2012-09 |
|
| Role of oxidative stress in methamphetamine-induced dopaminergic toxicity mediated by protein kinase Cδ. | 2012-06-15 |
|
| Rottlerin induces apoptosis of HT29 colon carcinoma cells through NAG-1 upregulation via an ERK and p38 MAPK-dependent and PKC δ-independent mechanism. | 2012-04-15 |
|
| Dual function of protein kinase C (PKC) in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced manganese superoxide dismutase (MnSOD) expression: activation of CREB and FOXO3a by PKC-alpha phosphorylation and by PKC-mediated inactivation of Akt, respectively. | 2011-08-26 |
|
| Protein kinase Ctheta is a specific target for inhibition of the HIV type 1 replication in CD4+ T lymphocytes. | 2011-08-05 |
|
| All-trans retinoic acid and a novel synthetic retinoid tamibarotene (Am80) differentially regulate CD38 expression in human leukemia HL-60 cells: possible involvement of protein kinase C-delta. | 2011-08 |
|
| Effects of manganese on tyrosine hydroxylase (TH) activity and TH-phosphorylation in a dopaminergic neural cell line. | 2011-07-15 |
|
| Nrf2-mediated adaptive response to cadmium-induced toxicity involves protein kinase C delta in human 1321N1 astrocytoma cells. | 2011-07 |
|
| Inhibition of PKCδ reduces cisplatin-induced nephrotoxicity without blocking chemotherapeutic efficacy in mouse models of cancer. | 2011-07 |
|
| Lipid raft-dependent death receptor 5 (DR5) expression and activation are critical for ursodeoxycholic acid-induced apoptosis in gastric cancer cells. | 2011-05 |
|
| Upregulation of heme oxygenase-1 as an adaptive mechanism for protection against crotonaldehyde in human umbilical vein endothelial cells. | 2011-03-25 |
|
| PKC-δ mediates TCDD-induced apoptosis of chondrocyte in ROS-dependent manner. | 2010-11 |
|
| 3-Caffeoyl, 4-dihydrocaffeoylquinic acid from Salicornia herbacea inhibits tumor cell invasion by regulating protein kinase C-delta-dependent matrix metalloproteinase-9 expression. | 2010-10-05 |
|
| Protective role of taurine against arsenic-induced mitochondria-dependent hepatic apoptosis via the inhibition of PKCdelta-JNK pathway. | 2010-09-07 |
|
| Lead-induced accumulation of beta-amyloid in the choroid plexus: role of low density lipoprotein receptor protein-1 and protein kinase C. | 2010-09 |
|
| Puerarin suppresses AGEs-induced inflammation in mouse mesangial cells: a possible pathway through the induction of heme oxygenase-1 expression. | 2010-04-15 |
|
| Novel screening method for potential skin-whitening compounds by a luciferase reporter assay. | 2010 |
|
| Protein kinase C-delta mediates down-regulation of heterogeneous nuclear ribonucleoprotein K protein: involvement in apoptosis induction. | 2009-11-15 |
|
| Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling. | 2009-09-22 |
|
| Protein kinase Cdelta stimulates proteasome-dependent degradation of C/EBPalpha during apoptosis induction of leukemic cells. | 2009-08-07 |
|
| Tamoxifen inhibits tumor cell invasion and metastasis in mouse melanoma through suppression of PKC/MEK/ERK and PKC/PI3K/Akt pathways. | 2009-07-15 |
|
| Angiotensin II induces renal plasminogen activator inhibitor-1 and cyclooxygenase-2 expression post-transcriptionally via activation of the mRNA-stabilizing factor human-antigen R. | 2009-04 |
|
| Induction of COX-2 in human airway cells by manganese: role of PI3K/PKB, p38 MAPK, PKCs, Src, and glutathione depletion. | 2009-02 |
|
| Quercetin inhibition of tumor invasion via suppressing PKC delta/ERK/AP-1-dependent matrix metalloproteinase-9 activation in breast carcinoma cells. | 2008-09 |
|
| Chlorpromazine attenuates pancreatic beta-cell function and mass through IRS2 degradation, while exercise partially reverses the attenuation. | 2008-07 |
|
| Heme oxygenase-1 mediates the anti-inflammatory effect of Curcumin within LPS-stimulated human monocytes. | 2008-06 |
|
| Acrolein induces heme oxygenase-1 through PKC-delta and PI3K in human bronchial epithelial cells. | 2008-04 |
|
| Regulation of mTOR and S6K1 activation by the nPKC isoforms, PKCepsilon and PKCdelta, in adult cardiac muscle cells. | 2007-12 |
|
| Up-regulation of cyclooxygenase-2 by cobalt chloride-induced hypoxia is mediated by phospholipase D isozymes in human astroglioma cells. | 2007-12 |
|
| P2Y nucleotide receptor signaling through MAPK/ERK is regulated by extracellular matrix: involvement of beta3 integrins. | 2007-10 |
|
| Cytotoxicity of paraquat in microglial cells: Involvement of PKCdelta- and ERK1/2-dependent NADPH oxidase. | 2007-09-05 |
|
| Regulation of heme oxygenase-1 expression by demethoxy curcuminoids through Nrf2 by a PI3-kinase/Akt-mediated pathway in mouse beta-cells. | 2007-09 |
|
| Acrolein induces cyclooxygenase-2 and prostaglandin production in human umbilical vein endothelial cells: roles of p38 MAP kinase. | 2007-06 |
|
| Curcumin-induced GADD153 upregulation: modulation by glutathione. | 2007-05-15 |
|
| Microarray-based kinase inhibition assay by gold nanoparticle probes. | 2007-01-15 |
|
| Involvement of protein kinase Cdelta in iron chelator-induced IL-8 production in human intestinal epithelial cells. | 2007-01-09 |
|
| Coadministration of sorafenib with rottlerin potently inhibits cell proliferation and migration in human malignant glioma cells. | 2006-12 |
|
| Mallotoxin is a novel human ether-a-go-go-related gene (hERG) potassium channel activator. | 2006-11 |
|
| Acetaldehyde inhibits PPARgamma via H2O2-mediated c-Abl activation in human hepatic stellate cells. | 2006-10 |
|
| Transcriptional up-regulation of MMP12 and MMP13 by asbestos occurs via a PKCdelta-dependent pathway in murine lung. | 2006-05 |
|
| Increasing ornithine decarboxylase activity is another way of prolactin preventing methotrexate-induced apoptosis: crosstalk between ODC and BCL-2. | 2006-03 |
|
| Role of PKC isoforms in the Fc(gamma)R-mediated inhibition of LPS-stimulated IL-12 secretion by macrophages. | 2006-02 |
|
| Macrophage migration inhibitory factor: a mediator of matrix metalloproteinase-2 production in rheumatoid arthritis. | 2006 |
|
| NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. | 2005-12-21 |
Sample Use Guides
Xenograft tumor
model in nude mice: mice were randomized into 4 treatment groups (control, DMSO, rottlerin 4 mg/kg, and rottlerin 2 mg/kg) with 5 mice per group. All the mice were
injected intraperitoneally daily for 4 weeks. Tumors were smaller in the experimental
groups than the control and DSMO groups, and tumors
were smaller in the rottlerin 4 mg/kg group than the rottlerin
2 mg/kg group.
Route of Administration:
Intraperitoneal
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DTXSID30231502
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Rottlerin
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82-08-6
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E29LP3ZMUH
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C085746
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94525
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m9675
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56346
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201-395-4
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SUBSTANCE RECORD
