2222-07-3 Usage
Uses
Used in Pharmaceutical Industry:
CUCURBITACIN I is used as a pharmaceutical agent for its anti-inflammatory, antipyretic, and analgesic properties. It has been found to inhibit the production of pro-inflammatory cytokines and modulate immune responses, making it a potential candidate for the treatment of inflammatory diseases.
Used in Cancer Therapy:
CUCURBITACIN I is used as an anticancer agent due to its ability to induce apoptosis, arrest cell cycle progression, and inhibit angiogenesis in various cancer cell lines. It has shown potential against a range of cancers, including breast, lung, and prostate cancer, by targeting multiple signaling pathways and molecular targets involved in cancer development and progression.
Used in Drug Delivery Systems:
To enhance the bioavailability, solubility, and therapeutic efficacy of CUCURBITACIN I, various drug delivery systems have been developed. These systems, such as nanoparticles, liposomes, and hydrogels, aim to improve the stability, targeted delivery, and controlled release of CUCURBITACIN I, thereby enhancing its pharmacological effects and reducing side effects.
Used in Cosmetic Industry:
CUCURBITACIN I is used as an active ingredient in cosmetic products for its anti-aging and skin-whitening properties. It has been reported to inhibit the activity of tyrosinase, a key enzyme involved in melanin synthesis, thus reducing skin pigmentation and promoting a lighter skin tone.
Used in Agricultural Industry:
CUCURBITACIN I is used as a natural pesticide and insect repellent in agriculture. It has been found to possess insecticidal and repellent properties against various pests, such as aphids, whiteflies, and mosquitoes, making it a potential alternative to synthetic chemical pesticides.
Biological Activity
Selective inhibitor of STAT3/JAK2 signaling. Inhibits the activation of STAT3 and JAK2 and displays no activity on Src, Akt, ERK and JNK. Suppresses phosphotyrosine levels of STAT3, inhibits STAT3 DNA binding and STAT3-mediated gene expression. Induces apoptosis in cell lines expressing constitutively active tyrosine-phosphorylated STAT3.
Biochem/physiol Actions
Cucurbitacin I (JSI-124) is a novel selective inhibitor of the janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway with anti-proliferative and anti-tumor properties.
references
blaskovich ma, sun j, cantor a et al. discovery of jsi-124 (cucurbitacin i), a selective janus kinase/signal transducer and activator of transcription 3 signaling pathway inhibitor with potent antitumor activity against human and murine cancer cells in mice.cancer res. 2003 mar 15;63(6):1270-9.yu h, lee h, herrmann a et al. revisiting stat3 signalling in cancer: new and unexpected biological functions.nat rev cancer. 2014 nov;14(11):736-46. doi: 10.1038/nrc3818.song j, liu h, li z et al. cucurbitacin i inhibits cell migration and invasion and enhances chemosensitivity in colon cancer. oncol rep. 2015 apr;33(4):1867-71. qi j, xia g, huang cr et al. jsi-124 (cucurbitacin i) inhibits tumor angiogenesis of human breast cancer through reduction of stat3 phosphorylation. am j chin med. 2015;43(2):337-47.kim hj, kim jk et al. antiangiogenic effects of cucurbitacin-i. arch pharm res. 2015 feb;38(2):290-8. yuan g, yan sf, xue h et al. cucurbitacin i induces protective autophagy in glioblastoma in vitro and in vivo. j biol chem. 2014 apr 11;289(15):10607-19.
Check Digit Verification of cas no
The CAS Registry Mumber 2222-07-3 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 2,2,2 and 2 respectively; the second part has 2 digits, 0 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 2222-07:
(6*2)+(5*2)+(4*2)+(3*2)+(2*0)+(1*7)=43
43 % 10 = 3
So 2222-07-3 is a valid CAS Registry Number.
InChI:InChI=1/C30H42O7/c1-25(2,36)12-11-21(33)30(8,37)23-19(32)14-27(5)20-10-9-16-17(13-18(31)24(35)26(16,3)4)29(20,7)22(34)15-28(23,27)6/h9,11-13,17,19-20,23,31-32,36-37H,10,14-15H2,1-8H3/b12-11+
2222-07-3Relevant articles and documents
Cucurbitacin derivatives and preparation method thereof
-
Paragraph 0129, (2018/04/21)
The invention discloses multiple new derivatives of cucurbitacin-B and cucurbitacin-E and salts of the new derivatives, and also discloses a preparation method of the new derivatives. As the new derivatives and the salts thereof have the same basic structures as cucurbitacin-B and cucurbitacin-E respectively, the nature of the new derivatives and the salts thereof is basically the same as that ofcucurbitacin-B and cucurbitacin-E, and the new derivatives and the salts thereof have good anti-cancer, anti-virus, anti-inflammation and liver protection effects with low toxic and side effects.
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.
Cucurbitacin E as a new inhibitor of cofilin phosphorylation in human leukemia U937 cells
Nakashima, Souichi,Matsuda, Hisashi,Kurume, Ai,Oda, Yoshimi,Nakamura, Seikou,Yamashita, Masayuki,Yoshikawa, Masayuki
experimental part, p. 2994 - 2997 (2010/08/20)
Cucurbitane-type triterpenes, cucurbitacins B and E, were reported to exhibit cytotoxic effects in several cell lines mediated by JAK/STAT3 signaling. However, neither compound inhibited phosphorylation of STAT3 in human leukemia (U937) cells at low concentrations. We therefore synthesized a biotin-linked cucurbitacin E to isolate target proteins based on affinity for the molecule. As a result, cofilin, which regulates the depolymerization of actin, was isolated and suggested to be a target. Cucurbitacins E and I inhibited the phosphorylation of cofilin in a concentration-dependent manner, and their effective concentrations having the same range as the concentrations at which they had cytotoxic effects in U937 cells. In addition, the fibrous-/globular-actin ratio was decreased after treatment with cucurbitacin E in HT1080 cells. These findings suggested that the inhibition of cofilin's phosphorylation increased the severing activity of cofilin, and then the depolymerization of actin was enhanced after treatment with cucurbitacin E at lower concentrations.
CUCURBITACIN COMPOUNDS
-
Page/Page column 7-8, (2008/06/13)
Cucurbitacins, cucurbitacin derivatives, and methods for making and using the same are provided.
