CINOBUFOTALIN

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H34O7
Molecular Weight	458.544
Optical Activity	UNSPECIFIED
Defined Stereocenters	10 / 10
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)O[C@H]1[C@H]2O[C@]23[C@@H]4CC[C@]5(O)C[C@@H](O)CC[C@]5(C)[C@H]4CC[C@]3(C)[C@H]1C6=COC(=O)C=C6

InChI

InChIKey=KBKUJJFDSHBPPA-ZNCGZLKOSA-N

InChI=1S/C26H34O7/c1-14(27)32-21-20(15-4-5-19(29)31-13-15)24(3)10-7-17-18(26(24)22(21)33-26)8-11-25(30)12-16(28)6-9-23(17,25)2/h4-5,13,16-18,20-22,28,30H,6-12H2,1-3H3/t16-,17-,18+,20-,21+,22+,23+,24+,25-,26+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25724183 | https://www.ncbi.nlm.nih.gov/pubmed/25201730

Cinobufotalin, the bufadienolide isolated from toad venom, has displayed antitumor activities in many in vitro systems. It has been shown that cinobufotalin induced significant apoptosis in cultured human lymphoma U-937 cells. It induced DNA fragmentation, mitochondrial membrane potential decrease, and reactive oxygen species (ROS) production in U-937 cells. Cinobufotalin induces cytotoxic effect in cultured lung cancer cells. Cinobufotalin (1/5 mg/kg, i.p. twice daily, for 7 days) significantly inhibited A549 xenograft growth in mice. Further, same cinobufotalin administration improved mice survival at week five. Cinobufotalin administration didn’t significantly affect mice body weight, indicating the relative safety of this regimen. Thus, cinobufotalin inhibits A549 xenograft growth in vivo and improves mice survival.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Apoptosis 156 Target ID: map04210 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27699589 \| https://www.ncbi.nlm.nih.gov/pubmed/25724183 \| https://www.ncbi.nlm.nih.gov/pubmed/22898211	Activator 1447
Hepatitis B virus 8 Target ID: CHEMBL613497 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9772592	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Cancer 609 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25724183	Primary	Preclinical	Unknown Approved Use Unknown
Chronic hepatitis B 16 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8111200	Primary	Phase I 438	Unknown Approved Use Unknown
Progressive gastric cancer 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18386568	Palliative	Phase I 438	Unknown Approved Use Unknown

AUC

Value	Dose	Co-administered	Analyte	Population
2.6 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31156437	2.5 mg/kg single, intravenous dose: 2.5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		CINOBUFOTALIN plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
13.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31156437	2.5 mg/kg single, intravenous dose: 2.5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		CINOBUFOTALIN plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741	P-gp 2052 CYP2E1 729 CYP1A2 1197 CYP2A6 626 CYP2B6 776 CYP2C8 810 CYP2C19 1119

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28184922/	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1197	substrate 4014 Sources: https://dmd.aspetjournals.org/content/39/4/675	no
CYP2A6 626	substrate 4014 Sources: https://dmd.aspetjournals.org/content/39/4/675	no
CYP2B6 776	substrate 4014 Sources: https://dmd.aspetjournals.org/content/39/4/675	no
CYP2C19 1119	substrate 4014 Sources: https://dmd.aspetjournals.org/content/39/4/675	no
CYP2C8 810	substrate 4014 Sources: https://dmd.aspetjournals.org/content/39/4/675	no
CYP2C9 1193	substrate 4014 Sources: https://dmd.aspetjournals.org/content/39/4/675	no
CYP2D6 1388	substrate 4014 Sources: https://dmd.aspetjournals.org/content/39/4/675	no
CYP2E1 729	substrate 4014 Sources: https://dmd.aspetjournals.org/content/39/4/675	no
CYP3A4 1946	substrate 4014 Sources: https://dmd.aspetjournals.org/content/39/4/675	yes [Km 16 uM]
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31156437/	yes

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P0039FV	https://www.1pchem.com/search?query=1P0039FV
AK Scientific	3551AH	https://aksci.com/item_detail.php?cat=3551AH
AstaTech	41978	http://astatechinc.com/CPSResult.php?CRNO=41978
Biopurify Phytochemicals	BP0367	https://www.phytopurify.com/search.do?a=s&searchtype=3&psize=10&q=BP0367&searchhtmp=simplesearch&t=1
BLD Pharm	BD121391	http://www.bldpharm.com/search/Search.html?keyword=BD121391
Chem Scene	CS-3698	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3698
eMolecules	535749	https://orderbb.emolecules.com/search/#?query=535749
mcule	MCULE-1278810623	https://mcule.com/MCULE-1278810623/
MedChem Express	HY-N0880	https://www.medchemexpress.com/search.html?q=HY-N0880&ft=&fa=&fp=
MolPort	MolPort-003-804-228	https://www.molport.com/shop/molecule-link/MolPort-003-804-228
Specs	AO-774/41465370	http://www.specs.net/enter.php?specsid=AO-774/41465370
Toronto Research Chemicals	L330840	https://www.trc-canada.com/product-detail/?CatNum=L330840

PubMed

Title	Date	PubMed
Apoptotic cell death by the novel natural compound, cinobufotalin.	2012-09-30	22898211

Patents

Sample Use Guides

In Vivo Use Guide

Mice: 1.0 mg/kg of cinobufotalin; Cinobufotalin was injected intraperitoneally (i.p.) twice daily for 1 weeks

Route of Administration: Intraperitoneal

In Vitro Use Guide

The survival of A549 cells, detected by MTT assay, was significantly inhibited by cinobufotalin. The cell viability decreased to 99.2 ± 9.1%, 65.9 ± 6.0%, 44.8 ± 3.5%, 34.8 ± 5.0% and 23.5 ± 3.3% of control group after 0.1 uM, 0.5 uM, 1.0 uM, 5.0 uM and 10.0 uM of cinobufotalin treatment. Results from the Trypan blue staining assay demonstrated that cinobufotalin (0.5–10 uM) significantly induced A549 cell death, and the effect was once again concentrationdependent. In two other human lung cancer cell lines (H460 and HTB-58), cinobufotalin (1.0 uM) similarly inhibited cancer cell survival.

Name

Type

Language

CINOBUFOTALIN

Common Name

English

NSC-90326

Preferred Name

English

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

Common Name

English

CINOBUFOTALIN [MI]

Common Name

English

Cinobufotalin [WHO-DD]

Common Name

English

CINOBUFAGIN METABOLITE M-2

Common Name

English

14,15.BETA.-EPOXY-3.BETA.,5,16.BETA.-TRIHYDROXY-5.BETA.-BUFA-20,22-DIENOLIDE 16-ACETATE

Common Name

English

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

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C129986