CUCURBITACIN I

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C30H42O7
Molecular Weight	514.6503
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1([C@H](O)C[C@@]2(C)[C@]3([H])CC=C4[C@@]([H])(C=C(O)C(=O)C4(C)C)[C@]3(C)C(=O)C[C@]12C)[C@@](C)(O)C(=O)\C=C\C(C)(C)O

InChI

InChIKey=NISPVUDLMHQFRQ-MKIKIEMVSA-N

InChI=1S/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+/t17-,19-,20+,23+,27+,28-,29+,30+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C30H42O7
Molecular Weight	514.6503
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	7 / 8
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12649187

Cucurbitacin I (JSI-124) is a novel selective triterpenoid that acts as a potent inhibitor of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway with anti-proliferative and anti-tumor properties. Cucurbitacin I specifically suppresses levels of tyrosine phosphorylated STAT3 in v-Src-transformed NIH 3T3 cells and in A549 cells (IC50 = 500 nM) resulting in inhibition of STAT3 DNA binding and reduced STAT3-mediated gene transcription. It also suppresses JAK2 phosphorylation but does not affect Src, ERK, JNK or Akt. In nude mice, cucurbitacin I (1 mg/kg/day) suppressed the growth of various tumors expressing constitutively active STAT3.1 It promotes the differentiation of dendritic cells and macrophages and enhances the effect of cancer immunotherapy. Cucurbitacin I (1 µM for 2 hours) reduced clonogenicity of nasopharyngeal carcinoma cells in vitro and suppresses tumor growth in mice (1.3 mg/kg).

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Leukocyte adhesion glycoprotein LFA-1 alpha 1 Target ID: CHEMBL1803 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7852999	Inhibitor 8297	0.95 µM [IC50]
Heat shock protein HSP90 35 Target ID: CHEMBL2095165 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25756299	Inhibitor 8297
Jak-STAT signaling pathway 9 Target ID: map04630 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23386688	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Otitis media with effusion 1 Sources: https://clinicaltrials.gov/ct2/show/NCT02858388	Primary		Phase III 656	Unknown Approved Use Unknown
Osteosarcoma 22 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27840900	Primary		Basic research	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
mMRP 1 P-gp 1461	UGT1A3 422 UGT1A4 347 UGT1A7 236 UGT1A8 283 UGT1A10 291 UGT1A6 307 UGT2B4 249 UGT1A1 418 UGT1A9 380 UGT2B7 389 UGT2B15 203 UGT2B17 213 SULT 5

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16904803/ \| https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=377020200	yes [IC50 181 uM]
mMRP 1	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/pii/S0963996912000634	yes [Inhibition 2 uM]

Drug as victim

Target	Modality	Activity
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	major
UGT2B17 213	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	major
UGT1A7 236	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	minor
UGT1A6 307	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	no
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	no
UGT2B4 249	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	no
UGT2B7 389	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	no
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	unlikely
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	unlikely
UGT1A8 283	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	unlikely
UGT2B15 203	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	unlikely
UGT1A10 291	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	weak
SULT 5	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	yes

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P019GB6	https://www.1pchem.com/search?query=1P019GB6
ApexBio Technology	A4512	https://www.apexbt.com/catalogsearch/result/?q=A4512
Apollo Scientific	BIDF1005	http://www.apolloscientific.co.uk/chemical_results.php?qstext=BIDF1005&product_group=%25&search_fieldname=header_search
Cayman Chemical	14747	http://www.caymanchem.com/app/template/Product.vm/catalog/14747
Chem Scene	CS-5431	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5431
MedChem Express	HY-N1405	https://www.medchemexpress.com/search.html?q=HY-N1405&ft=&fa=&fp=
MolPort	MolPort-023-276-142	https://www.molport.com/shop/molecule-link/MolPort-023-276-142
Tocris	1571	https://www.tocris.com/search.php?Type=QuickSearch&Value=1571
eMolecules	48600941	https://orderbb.emolecules.com/search/#?query=48600941
mcule	MCULE-8177568528	https://mcule.com/MCULE-8177568528/

PubMed

Title	Date	PubMed
Glycine-extended gastrin inhibits apoptosis in Barrett's oesophageal and oesophageal adenocarcinoma cells through JAK2/STAT3 activation.	2009 Apr	19153190
The anti-inflammatory effects of adiponectin are mediated via a heme oxygenase-1-dependent pathway in rat Kupffer cells.	2010 Apr	20052772
The cucurbitacins E, D and I: investigation of their cytotoxicity toward human chondrosarcoma SW 1353 cell line and their biotransformation in man liver.	2013 Feb 4	23194827
Cucurbitacin-I, a natural cell-permeable triterpenoid isolated from Cucurbitaceae, exerts potent anticancer effect in colon cancer.	2014 Aug 5	24858077
Cucurbitacin B and cucurbitacin I suppress adipocyte differentiation through inhibition of STAT3 signaling.	2014 Feb	24316209
STAT3-dependent VEGF production from keratinocytes abrogates dendritic cell activation and migration by arsenic: a plausible regional mechanism of immunosuppression in arsenical cancers.	2015 Feb 5	25559853

Patents

Sample Use Guides

In Vivo Use Guide

Sinuclean Nebules is a solution of cucurbitacins B,D,I,E (glycosylated triterpenes) 45 mcg/nostril/day for two cycles of 10 consecutive days. Cycles are interrupted by a period of 7 days.

Route of Administration: Nasal

In Vitro Use Guide

For measurement of cell proliferation, the Five human OS cell lines (143B, HOS, MG63, SAOS-2, and HUO9) were placed in monolayer culture at a density of 3.0x10^4 cells/well (100 μl). For dose-response tests, cells were exposed to media with various concentrations (10 nM, 100 nM, 1.0 μM and 10 μM) of cucurbitacin I or DMSO (negative control) for 24 h. For time-response tests, cells were exposed to media with 10 mM cucurbitacin I or DMSO for 12, 24 or 48 h.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:16:53 GMT 2023` Edited by `admin` on `Sat Dec 16 09:16:53 GMT 2023`
Record UNII	SHQ47990PH
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CUCURBITACIN I

Common Name

English

ELATERICIN B

Common Name

English

NSC-112167

Code

English

19-NORLANOSTA-1,5,23-TRIENE-3,11,22-TRIONE, 2,16,20,25-TETRAHYDROXY-9-METHYL-, (9.BETA.,10.ALPHA.,16.ALPHA.,23E)-

Systematic Name

English

NSC-521777

Code

English

JSI-124

Code

English

Code System Code Type Description

FDA UNII

SHQ47990PH