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

[H][C@@]12CC[C@]3(O)C[C@@H](O)CC[C@]3(C)[C@@]1([H])CC[C@]4(C)[C@H]([C@@H](OC(C)=O)[C@H]5O[C@@]245)C6=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

Molecular Formula	C26H34O7
Molecular Weight	458.544
Charge	0
Count

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

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 155 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 1430
Hepatitis B virus 8 Target ID: CHEMBL613497 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9772592	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Cancer 592 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 428	Unknown Approved Use Unknown
Progressive gastric cancer 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18386568	Palliative	Phase I 428	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 1737	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461	P-gp 1537 CYP2E1 667 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C19 991

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
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://dmd.aspetjournals.org/content/39/4/675	no
CYP2A6 543	substrate 3367 Sources: https://dmd.aspetjournals.org/content/39/4/675	no
CYP2B6 664	substrate 3367 Sources: https://dmd.aspetjournals.org/content/39/4/675	no
CYP2C19 991	substrate 3367 Sources: https://dmd.aspetjournals.org/content/39/4/675	no
CYP2C8 693	substrate 3367 Sources: https://dmd.aspetjournals.org/content/39/4/675	no
CYP2C9 1037	substrate 3367 Sources: https://dmd.aspetjournals.org/content/39/4/675	no
CYP2D6 1217	substrate 3367 Sources: https://dmd.aspetjournals.org/content/39/4/675	no
CYP2E1 667	substrate 3367 Sources: https://dmd.aspetjournals.org/content/39/4/675	no
CYP3A4 1737	substrate 3367 Sources: https://dmd.aspetjournals.org/content/39/4/675	yes [Km 16 uM]
P-gp 1537	substrate 3367 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
BLD Pharm	BD121391	http://www.bldpharm.com/search/Search.html?keyword=BD121391
Biopurify Phytochemicals	BP0367	https://www.phytopurify.com/search.do?a=s&searchtype=3&psize=10&q=BP0367&searchhtmp=simplesearch&t=1
Chem Scene	CS-3698	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3698
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
eMolecules	535749	https://orderbb.emolecules.com/search/#?query=535749
mcule	MCULE-1278810623	https://mcule.com/MCULE-1278810623/

PubMed

Title	Date	PubMed
Apoptotic cell death by the novel natural compound, cinobufotalin.	2012 Sep 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.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:03:29 GMT 2023` Edited by `admin` on `Sat Dec 16 08:03:29 GMT 2023`
Record UNII	L0QBZ37386
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CINOBUFOTALIN

Common 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

NSC-90326

Code

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