Cinobufagin CAS 470-37-1

Introduction：Basic information about Cinobufagin CAS 470-37-1, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Cinobufagin Basic information

• Product Name: Cinobufagin
• Synonyms: RARECHEM BK HC T302;5b,20(22)-Bufadienolide-3b,16b-diol-14,15b-epoxy 16-acetate;CINOBUFAGIN95%,99%;CINOBUFAGIN(P);TRANS-3-PHENYLPROPENOIC ACID;TRANS-3-BENZENEPROPENOIC ACID;TRANS-CINNAMYLIC ACID;Cinobufagin std.
• CAS: 470-37-1
• MF: C26H34O6
• MW: 442.55
• EINECS: 636-927-8
• Product Categories: chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;Steroids
• Mol File: 470-37-1.mol

Cinobufagin Chemical Properties

• Melting point: 133 °C(lit.)
• Boiling point: 300 °C(lit.)
• density: 1.261 g/cm3
• Fp: >230 °F
• storage temp.: 2-8°C
• solubility: DMF: 10 mg/ml; DMSO: 10 mg/ml; DMSO:PBS (pH 7.2) (1:2): 0.33 mg/ml
• pka: 15.10±0.70(Predicted)
• form: powder to crystal
• color: White to Light yellow
• InChIKey: SCULJPGYOQQXTK-QZXYOKJUNA-N
• SMILES: C[C@]12CC[C@]3([H])[C@]4(CC[C@H](O)C[C@@]4([H])CC[C@@]3([H])[C@@]31O[C@@H]3[C@H](OC(=O)C)[C@@H]2C1=COC(=O)C=C1)C |&1:1,4,6,9,12,16,18,20,21,26,r|

Safety Information

• Hazard Codes: Xi,T+,Xn
• Risk Statements: 36/37/38-26/27/28-42/43-20/22
• Safety Statements: 26-36-45-36/37/39-22-24/25
• RIDADR: UN 2811 6.1/PG 1
• WGK Germany: 3
• RTECS: GD7850000
• HazardClass: 6.1(a)
• PackingGroup: II
• HS Code: 29322090
• Storage Class: 6.1A - Combustible acute toxic Cat. 1 and 2 very toxic hazardous materials
• Hazard Classifications: Acute Tox. 1 Inhalation Acute Tox. 2 Dermal Acute Tox. 2 Oral

Cinobufagin Usage And Synthesis

Description

Cinobufagin is a cardiotoxic bufanolide steroid secreted by the Asiatic toad Bufo gargarizans, having similar effects to digitalis and used in traditional Chinese medicine. It has potential antineoplastic activity and now is widely used in clinical practice, especially in anti-liver cancer. It has benn found to suppress cancer cell proliferation and cause apoptosis in cancer cells via a sequence of apoptotic modulators, including mitochondrial Bax and cytosolic chromosome c, and caspases 3, 8, and 9.

References

1. https://en.wikipedia.org/wiki/Cinobufagin
2. https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=689412
3. http://www.yourdictionary.com/cinobufagin
4. https://www.medchemexpress.com/cinobufagin.html

Description

Cinobufagin is a cardiotonic steroid that has been found in the skin of toads of genus Bufo and has diverse biological activities. It inhibits Na⁺/K⁺-ATPase activity in guinea pig heart ventricular muscle homogenates by 45% when used at a concentration of 0.3 μM. Cinobufagin is cytotoxic to HCT116 colorectal cancer cells in vitro with IC₅₀ values of less than 50 ng/ml at 48- and 72-hour time points and induces apoptosis in a concentration-dependent manner. In vivo, cinobufagin (10 mg/kg) reduces tumor growth in an HCT116 mouse xenograft model. Cinobufagin (1 μg/ml) inhibits LPS-induced expression of MHC class II, CD80, and CD86 and release of IL-6, IL-8, TNF-α, and IL-10 in human monocyte-derived dendritic cells. It also increases expression of the antimicrobial peptides hBD2 and hBD3 in dendritic cells. Cinobufagin exhibits dose-dependent antinociceptive effects in the hot-plate, acetic acid writhing, and formalin tests in mice.

Chemical Properties

Soluble in chloroform, methanol and other organic solvents, insoluble in water. Derived from the dried secretion of toads such as Bufo bufo gargarizans Cantor.

Uses

Cinobufagine is a major component of cinobufacini (huachansu), is an important cardenolidal steroid. Cinobufagine was shown to exhibit potent anti-cancer effects.

Definition

ChEBI: Cinobufagin is a steroid lactone. It is functionally related to a bufanolide.

in vivo

Cinobufagin (5 mg/kg for i.p., once a day for 10 days) inhibits xenograft growth by inducing cell apoptosis in tumor xenograft mice model^[1].
Cinobufagin (5 mg/kg for i.p., once a day for 10 days) suppresses tumor growth in both subcutaneous and intracranial U87MG-EGFR xenograft mouse models and increases the median survival of nude mice bearing intracranial U87MGEGFR tumors^[2].

• Animal Model: OCM1 cells tumor xenograft in Nu/Nu nude mice ^[1]
• Dosage: 5 mg/kg
• Administration: Intraperitoneal injection (i.p.), once a day for 10 days
• Result: Made the tumors grew more slowly than those treated with intraperitoneal injection of saline or untreated. Increased the expression of caspase-3 and PARP in tumor tissues and decreased Bcl-2 and Bcl-xl expression in mouse tumor tissues and increased expression of Bad and Bax.

• Animal Model: U87MG-EGFR subcutaneous and intracranial xenograft model^[2]
• Dosage: 5 mg/kg
• Administration: Intraperitoneal injection (i.p.), once a day for 10 days
• Result: Decreased the luminescence intensity of brain tumor about 70%. Decreased p-EGFR, p-STAT3, and p-Akt levels in the intracranial tumors as compared with the vehicles. Decreased Ki67 and active caspase-3 immunostaining of intracranial tumors.

References

[1] S TOMA. Metabolism and pharmacokinetics of cinobufagin.[J]. Xenobiotica, 1987, 17 10: 1195-1202. DOI: 10.3109/00498258709167411
[2] XING-SHENG LU. Preclinical study of cinobufagin as a promising anti-colorectal cancer agent[J]. Oncotarget, 2016, 8 1: 988-998. DOI: 10.18632/oncotarget.13519
[3] SHANSHAN XIE. Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity.[J]. ACS Applied Bio Materials, 2016: e0160734. DOI: 10.1371/journal.pone.0160734
[4] LONGSHENG XU. Alpha-7 Nicotinic Receptor-Targeted Cinobufagin Induces Antinociception and Inhibits NF-κB Signaling Pathway in DRG Neurons[J]. ACS Chemical Neuroscience, 2018, 10 1: 497-506. DOI: 10.1021/acschemneuro.8b00369