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)C(C(=O)\C=C\C3=CC=CC=C3)=C4OC(C)(C)C=CC4=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+
| Molecular Formula | C30H28O8 |
| Molecular Weight | 516.5385 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| Optical Activity | NONE |
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 |
|---|---|---|
| Dieldrin induces apoptosis by promoting caspase-3-dependent proteolytic cleavage of protein kinase Cdelta in dopaminergic cells: relevance to oxidative stress and dopaminergic degeneration. | 2003 |
|
| Induction of cIAP-2 in human colon cancer cells through PKC delta/NF-kappa B. | 2003 Dec 19 |
|
| Ca(2+)-independent protein kinase C activity is required for alpha1-adrenergic-receptor-mediated regulation of ribosomal protein S6 kinases in adult cardiomyocytes. | 2003 Jul 15 |
|
| Allyl alcohol activation of protein kinase C delta leads to cytotoxicity of rat hepatocytes. | 2003 May |
|
| Involvement of MAP-kinase, PI3-kinase and EGF-receptor in the stimulatory effect of Neurotensin on DNA synthesis in PC3 cells. | 2004 Aug 15 |
|
| Blockade of PKCdelta proteolytic activation by loss of function mutants rescues mesencephalic dopaminergic neurons from methylcyclopentadienyl manganese tricarbonyl (MMT)-induced apoptotic cell death. | 2004 Dec |
|
| Lipopolysaccharide induces matrix metalloproteinase-9 expression via a mitochondrial reactive oxygen species-p38 kinase-activator protein-1 pathway in Raw 264.7 cells. | 2004 Dec 1 |
|
| PKC-epsilon regulation of extracellular signal-regulated kinase: a potential role in phenylephrine-induced cardiocyte growth. | 2004 Jun |
|
| Localization of VEGFR-2 and PLD2 in endothelial caveolae is involved in VEGF-induced phosphorylation of MEK and ERK. | 2004 May |
|
| Gefitinib ("Iressa", ZD1839) inhibits SN38-triggered EGF signals and IL-8 production in gastric cancer cells. | 2005 Apr |
|
| Doxorubicin requires the sequential activation of caspase-2, protein kinase Cdelta, and c-Jun NH2-terminal kinase to induce apoptosis. | 2005 Aug |
|
| NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. | 2005 Dec 21 |
|
| Interferon-alpha-induced expression of phospholipid scramblase 1 through STAT1 requires the sequential activation of protein kinase Cdelta and JNK. | 2005 Dec 30 |
|
| Protein kinase Ctheta activity is involved in the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced signal transduction pathway leading to apoptosis in L-MAT, a human lymphoblastic T-cell line. | 2005 Feb |
|
| Phosphorylation-regulated nucleocytoplasmic trafficking of internalized fibroblast growth factor-1. | 2005 Feb |
|
| PKC delta-induced activation of MAPK pathway is required for bFGF-stimulated proliferation of coronary smooth muscle cells. | 2005 Jul 1 |
|
| Positive and negative transcriptional regulation of aromatase expression in human breast cancer tissue. | 2005 May |
|
| Cooperation of amphiregulin and insulin-like growth factor-1 inhibits Bax- and Bad-mediated apoptosis via a protein kinase C-dependent pathway in non-small cell lung cancer cells. | 2005 May 20 |
|
| Immunomodulatory drugs (IMiDs) increase the production of IL-2 from stimulated T cells by increasing PKC-theta activation and enhancing the DNA-binding activity of AP-1 but not NF-kappaB, OCT-1, or NF-AT. | 2005 Oct |
|
| Inhibitory effects of 12-O-tetradecanoylphorbol-13-acetate alone or in combination with all-trans retinoic acid on the growth of cultured human pancreas cancer cells and pancreas tumor xenografts in immunodeficient mice. | 2005 Oct |
|
| Macrophage migration inhibitory factor: a mediator of matrix metalloproteinase-2 production in rheumatoid arthritis. | 2006 |
|
| Coadministration of sorafenib with rottlerin potently inhibits cell proliferation and migration in human malignant glioma cells. | 2006 Dec |
|
| Role of PKC isoforms in the Fc(gamma)R-mediated inhibition of LPS-stimulated IL-12 secretion by macrophages. | 2006 Feb |
|
| Piceatannol upregulates endothelial heme oxygenase-1 expression via novel protein kinase C and tyrosine kinase pathways. | 2006 Feb |
|
| Retinoid-mediated stimulation of steroid sulfatase activity in myeloid leukemic cell lines requires RARalpha and RXR and involves the phosphoinositide 3-kinase and ERK-MAP kinase pathways. | 2006 Feb 1 |
|
| Increasing ornithine decarboxylase activity is another way of prolactin preventing methotrexate-induced apoptosis: crosstalk between ODC and BCL-2. | 2006 Mar |
|
| Transcriptional up-regulation of MMP12 and MMP13 by asbestos occurs via a PKCdelta-dependent pathway in murine lung. | 2006 May |
|
| Mallotoxin is a novel human ether-a-go-go-related gene (hERG) potassium channel activator. | 2006 Nov |
|
| Acetaldehyde inhibits PPARgamma via H2O2-mediated c-Abl activation in human hepatic stellate cells. | 2006 Oct |
|
| Microarray-based kinase inhibition assay by gold nanoparticle probes. | 2007 Jan 15 |
|
| Involvement of protein kinase Cdelta in iron chelator-induced IL-8 production in human intestinal epithelial cells. | 2007 Jan 9 |
|
| Acrolein induces cyclooxygenase-2 and prostaglandin production in human umbilical vein endothelial cells: roles of p38 MAP kinase. | 2007 Jun |
|
| Curcumin-induced GADD153 upregulation: modulation by glutathione. | 2007 May 15 |
|
| Cytotoxicity of paraquat in microglial cells: Involvement of PKCdelta- and ERK1/2-dependent NADPH oxidase. | 2007 Sep 5 |
|
| Heme oxygenase-1 mediates the anti-inflammatory effect of Curcumin within LPS-stimulated human monocytes. | 2008 Jun |
|
| Protein kinase Cdelta stimulates proteasome-dependent degradation of C/EBPalpha during apoptosis induction of leukemic cells. | 2009 Aug 7 |
|
| Induction of COX-2 in human airway cells by manganese: role of PI3K/PKB, p38 MAPK, PKCs, Src, and glutathione depletion. | 2009 Feb |
|
| Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling. | 2009 Sep 22 |
|
| Puerarin suppresses AGEs-induced inflammation in mouse mesangial cells: a possible pathway through the induction of heme oxygenase-1 expression. | 2010 Apr 15 |
|
| 3-Caffeoyl, 4-dihydrocaffeoylquinic acid from Salicornia herbacea inhibits tumor cell invasion by regulating protein kinase C-delta-dependent matrix metalloproteinase-9 expression. | 2010 Oct 5 |
|
| Lead-induced accumulation of beta-amyloid in the choroid plexus: role of low density lipoprotein receptor protein-1 and protein kinase C. | 2010 Sep |
|
| Protective role of taurine against arsenic-induced mitochondria-dependent hepatic apoptosis via the inhibition of PKCdelta-JNK pathway. | 2010 Sep 7 |
|
| 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 Aug 26 |
|
| Inhibition of PKCδ reduces cisplatin-induced nephrotoxicity without blocking chemotherapeutic efficacy in mouse models of cancer. | 2011 Jul |
|
| Lipid raft-dependent death receptor 5 (DR5) expression and activation are critical for ursodeoxycholic acid-induced apoptosis in gastric cancer cells. | 2011 May |
|
| 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 Apr 15 |
|
| Isorhamnetin protects against oxidative stress by activating Nrf2 and inducing the expression of its target genes. | 2014 Jan 15 |
|
| Naringin protects against anoxia/reoxygenation-induced apoptosis in H9c2 cells via the Nrf2 signaling pathway. | 2015 Apr |
|
| A HAMP promoter bioassay system for identifying chemical compounds that modulate hepcidin expression. | 2015 May |
|
| Protein kinase Cδ mediates trimethyltin-induced neurotoxicity in mice in vivo via inhibition of glutathione defense mechanism. | 2016 Apr |
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
| Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 19:00:15 GMT 2023
by
admin
on
Fri Dec 15 19:00:15 GMT 2023
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| Record UNII |
E29LP3ZMUH
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
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DTXSID30231502
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Rottlerin
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m9675
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56346
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