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

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

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	8 / 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 8504	0.95 µM [IC50]
Heat shock protein HSP90 35 Target ID: CHEMBL2095165 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25756299	Inhibitor 8504
Jak-STAT signaling pathway 9 Target ID: map04630 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23386688	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Otitis media with effusion 1 Sources: https://clinicaltrials.gov/ct2/show/NCT02858388	Primary		Phase III 665	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 1741	UGT1A3 470 UGT1A4 399 UGT1A7 249 UGT1A8 323 UGT1A10 331 UGT1A6 343 UGT2B4 278 UGT1A1 479 UGT1A9 423 UGT2B7 456 UGT2B15 236 UGT2B17 237 SULT 12

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1932	inhibitor 4027 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 4027 Sources: https://www.sciencedirect.com/science/article/pii/S0963996912000634	yes [Inhibition 2 uM]

Drug as victim

Target	Modality	Activity
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	major
UGT2B17 237	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	major
UGT1A7 249	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	minor
UGT1A6 343	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	no
UGT1A9 423	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	no
UGT2B4 278	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	no
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	no
UGT1A3 470	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	unlikely
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	unlikely
UGT1A8 323	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	unlikely
UGT2B15 236	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	unlikely
UGT1A10 331	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23194827/	weak
SULT 12	substrate 4014 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
eMolecules	48600941	https://orderbb.emolecules.com/search/#?query=48600941
mcule	MCULE-8177568528	https://mcule.com/MCULE-8177568528/
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

PubMed

Title	Date	PubMed
STAT3-dependent VEGF production from keratinocytes abrogates dendritic cell activation and migration by arsenic: a plausible regional mechanism of immunosuppression in arsenical cancers.	2015-02-05	25559853
Cucurbitacin-I, a natural cell-permeable triterpenoid isolated from Cucurbitaceae, exerts potent anticancer effect in colon cancer.	2014-08-05	24858077
Cucurbitacin B and cucurbitacin I suppress adipocyte differentiation through inhibition of STAT3 signaling.	2014-02	24316209
The cucurbitacins E, D and I: investigation of their cytotoxicity toward human chondrosarcoma SW 1353 cell line and their biotransformation in man liver.	2013-02-04	23194827
The anti-inflammatory effects of adiponectin are mediated via a heme oxygenase-1-dependent pathway in rat Kupffer cells.	2010-04	20052772
Glycine-extended gastrin inhibits apoptosis in Barrett's oesophageal and oesophageal adenocarcinoma cells through JAK2/STAT3 activation.	2009-04	19153190

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 `Mon Mar 31 22:36:15 GMT 2025` Edited by `admin` on `Mon Mar 31 22:36:15 GMT 2025`
Record UNII	SHQ47990PH
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CUCURBITACIN I

Common Name

English

JSI-124

Preferred 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

Code System Code Type Description

FDA UNII

SHQ47990PH