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Drug-Target Interaction

Drug

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PubChem ID:148189
Structure:
Synonyms:
(R)-6'-Hydroxy-3'-(hydroxymethyl)-2',4',6'-trimethylspiro(cyclopropane-1,5'-(5H)inden)-7'(6'H)-one
158440-71-2
6-(Hydroxymethyl)acylfulvene
6-Hydroxymethylacylfulvene
Acylfulvene, 6-(hydroxymethyl)-
D04614
HMAF
Irofulven
Irofulven (USAN/INN)
LS-146017
MGI 114
NCI60_030149
NSC 683863
NSC683863
Spiro(cyclopropane-1,5'(5H)-inden)-7'(6'H)-one,
Spiro(cyclopropane-1,5'(5H)-inden)-7'(6'H)-one, 6'-hydroxy-3'-(hydroxymethyl)-2',4',6'-trimethyl-, (R)-

Target

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Uniprot ID:MK03_HUMAN
Synonyms:
ERK-1
ERT2
Extracellular signal-regulated kinase 1
Insulin-stimulated MAP2 kinase
MAP kinase 1
MAPK 1
Microtubule-associated protein 2 kinase
Mitogen-activated protein kinase 3
p44-ERK1
p44-MAPK
EC-Numbers:2.7.11.24
Organism:Homo sapiens
Human
PDB IDs:2ZOQ
Structure:
2ZOQ

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----

References:

12014623
Irofulven (6-hydroxymethylacylfulvene, MGI 114)-induced apoptosis in human pancreatic cancer cells is mediated by ERK and JNK kinases.. Weixin Wang; Stephen J Waters; John R MacDonald; Caleb Roth; Shujun Shentu; James Freeman; Daniel D Von Hoff; Alexander R Miller (2002) Anticancer research display abstract
BACKGROUND: Pancreatic carcinoma resists chemotherapeutic mediation of apoptosis. Irofulven (MGI 114, 6-hydroxymethylacylfulvene) is a novel illudin S analogue that we have shown to induce caspase-mediated apoptosis in pancreatic carcinoma cell lines. MATERIALS AND METHODS: Westem blot analysis and kinase assays were used to demonstrate the activation of Erk 1/2 and JNK1 kinases following Irofulven administration in the presence and absence of selective kinase inhibitors. RESULTS: Irofulven activates JNK1 and Erk1/2, but not p38. The addition of the MAPK inhibitors, SB202190 and PD98059 (targeting JNK1 and Erk1/2 activation, respectively), prevents kinase activation and blocks Irofulven-induced activation of caspases -3, -7, -8 and -9. Blockade of either JNK1 or Erk1/2 results in a 50% decrease in apoptosis in MiaPaCa-2 cells treated with Irofulven. CONCLUSION: Our data demonstrated that JNK1 and Erk1/2 are activated by Irofulven treatment and that blockade of either MAPK subfamily decreases apoptosis by rendering Irofulven incapable of inducing caspase activation.