55903-92-9Relevant articles and documents
Cucurbitacin D Is a Disruptor of the HSP90 Chaperone Machinery
Hall, Jessica A.,Seedarala, Sahithi,Rice, Nichole,Kopel, Lucas,Halaweish, Fathi,Blagg, Brian S. J.
, p. 873 - 879 (2015/05/13)
Heat shock protein 90 (Hsp90) facilitates the maturation of many newly synthesized and unfolded proteins (clients) via the Hsp90 chaperone cycle, in which Hsp90 forms a heteroprotein complex and relies upon cochaperones, immunophilins, etc., for assistance in client folding. Hsp90 inhibition has emerged as a strategy for anticancer therapies due to the involvement of clients in many oncogenic pathways. Inhibition of chaperone function results in client ubiquitinylation and degradation via the proteasome, ultimately leading to tumor digression. Small molecule inhibitors perturb ATPase activity at the N-terminus and include derivatives of the natural product geldanamycin. However, N-terminal inhibition also leads to induction of the pro-survival heat shock response (HSR), in which displacement of the Hsp90-bound transcription factor, heat shock factor-1, translocates to the nucleus and induces transcription of heat shock proteins, including Hsp90. An alternative strategy for Hsp90 inhibition is disruption of the Hsp90 heteroprotein complex. Disruption of the Hsp90 heteroprotein complex is an effective strategy to prevent client maturation without induction of the HSR. Cucurbitacin D, isolated from Cucurbita texana, and 3-epi-isocucurbitacin D prevented client maturation without induction of the HSR. Cucurbitacin D also disrupted interactions between Hsp90 and two cochaperones, Cdc37 and p23.
New Cytotoxic Principles from Datisca glomerata
Sasamori, Hiroshi,Reddy, K. Sambi,Kirkup, Michael P.,Shabanowitz, Jeffrey,Lynn, David G.,at al.
, p. 1333 - 1347 (2007/10/02)
Datisca glomerata has been systematically fractionated by following cellular toxicity in an effort to identify previously uncharacterized cytotoxic principles.Several new cucurbitacin glycosides, including datiscosides B(8), C(3), D(9), E(4), F(5), G(6), and H(10) and the known compound datiscoside (1), as well as cucurbitacins B(11), D(2), and F(7) have been isolated and characterized.Structures were assigned to the compounds on the basis of their high field 1H n.m.r., 13C n.m.r., high-resolution mass spectra (CI, EI, and FD) and chemical interconversions.The structure of datiscoside C(3) was independently established by single-crystal X-ray analysis at 193 and 293 K.
