Cysmethynil binds ICMT:Zn2+

Stable Identifier
R-HSA-9656775
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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Cysmethnil is a small molecule inhibitor of ICMT that has been shown to reduce proliferation of cancer cell lines by promoting apoptosis (Winter-Vann et al, 2005; Wang et al, 2010; Judd et al, 2011; Sun et al, 2016; Manu et al, 2017). Cysmethynil is a poor candidate for clinical trials due to low solubility and other physical characteristics. A number of related small molecule inhibitors with improved physical properties are under investigation (Lau et al, 2014; Ramanujulu et al, 2013).

Literature References
PubMed ID Title Journal Year
12750467 Targeting Ras signaling through inhibition of carboxyl methylation: an unexpected property of methotrexate

Winter-Vann, AM, Kamen, BA, Bergo, MO, Young, SG, Melnyk, S, James, SJ, Casey, PJ

Proc. Natl. Acad. Sci. U.S.A. 2003
26706195 Inhibition of isoprenylcysteine carboxylmethyltransferase augments BCR-ABL1 tyrosine kinase inhibition-induced apoptosis in chronic myeloid leukemia

Sun, WT, Xiang, W, Ng, BL, Asari, K, Bunte, RM, Casey, PJ, Wang, M, Chuah, C

Exp. Hematol. 2016
24971579 An improved isoprenylcysteine carboxylmethyltransferase inhibitor induces cancer cell death and attenuates tumor growth in vivo

Lau, HY, Ramanujulu, PM, Guo, D, Yang, T, Wirawan, M, Casey, PJ, Go, ML, Wang, M

Cancer Biol. Ther. 2014
21661760 Discovery and SAR of methylated tetrahydropyranyl derivatives as inhibitors of isoprenylcysteine carboxyl methyltransferase (ICMT)

Judd, WR, Slattum, PM, Hoang, KC, Bhoite, L, Valppu, L, Alberts, G, Brown, B, Roth, B, Ostanin, K, Huang, L, Wettstein, D, Richards, B, Willardsen, JA

J. Med. Chem. 2011
20622895 Inhibition of isoprenylcysteine carboxylmethyltransferase induces autophagic-dependent apoptosis and impairs tumor growth

Wang, M, Hossain, MS, Tan, W, Coolman, B, Zhou, J, Liu, S, Casey, PJ

Oncogene 2010
28167504 Inhibition of Isoprenylcysteine Carboxylmethyltransferase Induces Cell-Cycle Arrest and Apoptosis through p21 and p21-Regulated BNIP3 Induction in Pancreatic Cancer

Manu, KA, Chai, TF, Teh, JT, Zhu, WL, Casey, PJ, Wang, M

Mol. Cancer Ther. 2017
23514631 Functionalized indoleamines as potent, drug-like inhibitors of isoprenylcysteine carboxyl methyltransferase (Icmt)

Ramanujulu, PM, Yang, T, Yap, SQ, Wong, FC, Casey, PJ, Wang, M, Go, ML

Eur J Med Chem 2013
Participants
Participant Of
hasEvent
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created
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