CINOBUFAGIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H34O6
Molecular Weight	442.5446
Optical Activity	UNSPECIFIED
Defined Stereocenters	10 / 10
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12CC[C@]3([H])[C@]([H])(CC[C@]4(C)[C@H]([C@@H](OC(C)=O)[C@H]5O[C@@]345)C6=COC(=O)C=C6)[C@@]1(C)CC[C@H](O)C2

InChI

InChIKey=SCULJPGYOQQXTK-OLRINKBESA-N

InChI=1S/C26H34O6/c1-14(27)31-22-21(15-4-7-20(29)30-13-15)25(3)11-9-18-19(26(25)23(22)32-26)6-5-16-12-17(28)8-10-24(16,18)2/h4,7,13,16-19,21-23,28H,5-6,8-12H2,1-3H3/t16-,17+,18+,19-,21+,22-,23-,24+,25-,26-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C26H34O6
Molecular Weight	442.5446
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	10 / 10
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=689412 | https://www.ncbi.nlm.nih.gov/pubmed/27176794 | https://www.ncbi.nlm.nih.gov/pubmed/29156710 | https://www.ncbi.nlm.nih.gov/pubmed/24187573 | https://www.ncbi.nlm.nih.gov/pubmed/18777599

Cinobufagin is a bufadienolide compound extracted from the dried venom secreted by the parotid glands of toads and one of the glycosides in the traditional Chinese medicine ChanSu, with potential antineoplastic activity. Cinobufagin has been shown to have clinical applications in cancer treatment as well as immunomodulatory and analgesic properties. Cinobufagin induces apoptosis of osteosarcoma cells through inactivation of Notch signaling. Cinobufagin induces autophagy-mediated cell death in human osteosarcoma U2OS cells through the ROS/JNK/p38 signaling pathway. Cinobufagin significantly relieved cancer pain in mice and raised their pain threshold, mainly upregulating the expression levels of beta-Endorphin and μ- opioid receptor in the hind paw tumor and adjacent tissue. In combination with gemcitabine-oxaliplatin cinobufagin was used in clinical trial for the treatment of locally advanced or metastatic gallbladder carcinoma.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
POMC/β-endorphin/μ-opioid receptor pathway 1 Target ID: POMC/β-endorphin/μ-opioid receptor pathway Sources: https://www.ncbi.nlm.nih.gov/pubmed/28002791	Activator 1430
Apoptosis 155 Target ID: map04210 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23164673	Activator 1430
ROS/JNK/p38 signaling pathway 1 Target ID: ROS/JNK/p38 signaling pathway Sources: https://www.ncbi.nlm.nih.gov/pubmed/27176794	Activator 1430

Conditions

Condition	Modality	Highest Phase	Product
Advanced gallbladder carcinoma 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18777599	Primary	Phase II 1132	Unknown Approved Use Unknown
Osteosarcoma 22 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29156710	Primary	Preclinical	Unknown Approved Use Unknown
Pain 614 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24187573 https://www.ncbi.nlm.nih.gov/pubmed/28002791	Primary	Preclinical	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781 substrate 1737	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461	CYP1A2 1054 CYP2E1 667 CYP2A6 543 CYP2C8 693 CYP2C19 991 CYP2B6 664

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1925	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/22178124/	yes
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/28184922/	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21205911/	no
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21205911/	no
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21205911/	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21205911/	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21205911/	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21205911/	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21205911/	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21205911/	no
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22178124/ \| https://pubmed.ncbi.nlm.nih.gov/21205911/	yes [Km 16 uM]

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific	8074AH	https://aksci.com/item_detail.php?cat=8074AH
Alfa Chemistry	ACM470371	http://www.alfa-chemistry.com/search.aspx?q=ACM470371
ApexBio Technology	N1154	https://www.apexbt.com/catalogsearch/result/?q=N1154
AstaTech	41977	http://astatechinc.com/CPSResult.php?CRNO=41977
BLD Pharm	BD9251	http://www.bldpharm.com/search/Search.html?keyword=BD9251
BioSynth	Q-100496	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/Q-100496
Biopurify Phytochemicals	BP0366	https://www.phytopurify.com/search.do?a=s&searchtype=3&psize=10&q=BP0366&searchhtmp=simplesearch&t=1
Chem Scene	CS-3697	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3697
Lab Seeker	SC-76202	http://www.labseeker.com/search.php?keywords=SC-76202&category=0
LabSeeker	SC-76202	http://www.labseeker.com/search.php?keywords=SC-76202&category=0
MedChem Express	HY-N0421	https://www.medchemexpress.com/search.html?q=HY-N0421&ft=&fa=&fp=
MolPort	MolPort-003-940-630	https://www.molport.com/shop/molecule-link/MolPort-003-940-630
MolPort	MolPort-039-052-340	https://www.molport.com/shop/molecule-link/MolPort-039-052-340
Molnova	M18578	https://www.molnova.com/en/serch-list.html?keywords=M18578
PI Chemicals	PI-10504	http://www.pipharm.com/catalog_products/PI-10504.html
Specs	AM-721/20741009	http://www.specs.net/enter.php?specsid=AM-721/20741009
TargetMol	-	https://www.targetmol.com/search?keyword=-
TargetMol	470-37-1	https://www.targetmol.com/search?keyword=470-37-1
TargetMol	BBP03916	https://www.targetmol.com/search?keyword=BBP03916
TargetMol	T3432	https://www.targetmol.com/search?keyword=T3432
Tetrahedron	TS70371	http://www.thsci.com/search.do?q=TS70371
Toronto Research Chemicals	C475500	https://www.trc-canada.com/product-detail/?CatNum=C475500
Toronto Research Chemicals	D443488	https://www.trc-canada.com/product-detail/?CatNum=D443488
W&J PharmaChem	50C237113	http://wjpharmachem.com/new/searcht.php?keyword=50C237113
eMolecules	535775	https://orderbb.emolecules.com/search/#?query=535775
eMolecules	58033477	https://orderbb.emolecules.com/search/#?query=58033477
eNovation Chemicals	D512308	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D512308&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-3387421370	https://mcule.com/MCULE-3387421370/
mcule	MCULE-5438039345	https://mcule.com/MCULE-5438039345/
mcule	MCULE-9483483702	https://mcule.com/MCULE-9483483702/

PubMed

Title	Date	PubMed
Cardiotonic steroids attenuate ERK phosphorylation and generate cell cycle arrest to block human hepatoma cell growth.	2011 Jul	21215801
The glycogen synthase kinase-3β/nuclear factor-kappa B pathway is involved in cinobufagin-induced apoptosis in cultured osteosarcoma cells.	2013 Apr 12	23164673

Patents

Sample Use Guides

In Vivo Use Guide

2-3 h infusion (20 mL/m2) (0.5 g/mL) in 500 mL of 50 g/L glucose solution on days 3-11

Route of Administration: Intravenous

In Vitro Use Guide

The survival rates of cinobufagin (0–300 nM) in 143B cells after 24, 48 and 72 h were investigated. Cinobufagin (100 nM) inhibited ~ 50% proliferation of 143 cells and the half-maximal inhibitory concentration (IC50) values were ~ 98–103 nM after 48 h treatment.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 11:22:52 UTC 2023` Edited by `admin` on `Sat Dec 16 11:22:52 UTC 2023`
Record UNII	T9PSN4R8IR
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CINOBUFAGIN

Common Name

English

BUFA-20,22-DIENOLIDE, 16-(ACETYLOXY)-14,15-EPOXY-3-HYDROXY-, (3- .BETA.,5-.BETA.,15-.BETA.,16-.BETA.)-

Systematic Name

English

Cinobufagin [WHO-DD]

Common Name

English

NSC-90325

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C274