Flavokawain B | CAS#1775-97-9 | UCK2 inhibitor

MedKoo Cat#: 562061 | Name: Flavokawain B

Featured

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Flavokawain B is a natural UCK2 inhibitor. It has been shown to bind to the cavity of R273H mutant p53 and restore wild-type p53 functions

Chemical Structure

Flavokawain B

CAS#1775-97-9

Theoretical Analysis

MedKoo Cat#: 562061

Name: Flavokawain B

CAS#: 1775-97-9

Chemical Formula: C17H16O4

Exact Mass: 284.1049

Molecular Weight: 284.31

Elemental Analysis: C, 71.82; H, 5.67; O, 22.51

Price and Availability

Size	Price	Availability
5mg	USD 350.00	2 Weeks
10mg	USD 550.00	2 Weeks
25mg	USD 950.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

Flavokawain B; Flavokawain-B; FlavokawainB; Flavokavain B; Flavokavin B; Persicochalcone

IUPAC/Chemical Name

(E)-1-(2-Hydroxy-4,6-dimethoxyphenyl)-3-phenylprop-2-en-1-one

InChi Key

QKQLSQLKXBHUSO-CMDGGOBGSA-N

InChi Code

InChI=1S/C17H16O4/c1-20-13-10-15(19)17(16(11-13)21-2)14(18)9-8-12-6-4-3-5-7-12/h3-11,19H,1-2H3/b9-8+

SMILES Code

O=C(C1=C(OC)C=C(OC)C=C1O)/C=C/C2=CC=CC=C2

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Flavokawain B (Flavokavain B) is a chalcone isolated from the root extracts of kava-kava plant and a potent apoptosis inducer for inhibiting the growth of various cancer cell lines.

In vitro activity:

The inhibition of Ubc12 neddylation was shown by non-denaturing Western blotting analysis, and an increasing dose of FKB (Flavokawain B) was able to inhibit neddylation to Ubc12 (Fig. 2b, top). The relative density of NEDD8-Ubc12 to the control was analyzed to have an estimated IC50 of approximately11μM (Fig. 2b, bottom). These results suggest that FKB inhibits neddylation by hindering NAE1 activities. Reference: Cell Commun Signal. 2019; 17: 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423783/

In vivo activity:

However, with the time course, the effect of intraperitoneal FKB (Flavokawain B) treatment on A375-xenograft tumor growth resulted in the inhibition of tumor volume (Figure 12B). After 26 days of therapy, the xenograft tumors excised from the mice were further evaluated and it was revealed that intraperitoneal administration of FKB treatment resulted in a dramatic retardation of tumor growth, signifying in vivo anti-tumor properties for FKB (Figure 12C–E). Reference: Cancers (Basel). 2020 Oct; 12(10): 2936. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600613/

	Solvent	mg/mL	mM
Solubility
	DMSO	32.3	113.71
	DMF	30.0	105.52
	Ethanol	10.0	35.17

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 284.31 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Li X, Pham V, Tippin M, Fu D, Rendon R, Song L, Uchio E, Hoang BH, Zi X. Flavokawain B targets protein neddylation for enhancing the anti-prostate cancer effect of Bortezomib via Skp2 degradation. Cell Commun Signal. 2019 Mar 18;17(1):25. doi: 10.1186/s12964-019-0338-2. PMID: 30885218; PMCID: PMC6423783. 2. Hseu YC, Huang YC, Thiyagarajan V, Mathew DC, Lin KY, Chen SC, Liu JY, Hsu LS, Li ML, Yang HL. Anticancer activities of chalcone flavokawain B from Alpinia pricei Hayata in human lung adenocarcinoma (A549) cells via induction of reactive oxygen species-mediated apoptotic and autophagic cell death. J Cell Physiol. 2019 Aug;234(10):17514-17526. doi: 10.1002/jcp.28375. Epub 2019 Mar 7. PMID: 30847898. 3. Hseu YC, Chiang YC, Vudhya Gowrisankar Y, Lin KY, Huang ST, Shrestha S, Chang GR, Yang HL. The In Vitro and In Vivo Anticancer Properties of Chalcone Flavokawain B through Induction of ROS-Mediated Apoptotic and Autophagic Cell Death in Human Melanoma Cells. Cancers (Basel). 2020 Oct 12;12(10):2936. doi: 10.3390/cancers12102936. Erratum in: Cancers (Basel). 2021 Jan 15;13(2): PMID: 33053749; PMCID: PMC7600613. 4. Chang CT, Hseu YC, Thiyagarajan V, Lin KY, Way TD, Korivi M, Liao JW, Yang HL. Chalcone flavokawain B induces autophagic-cell death via reactive oxygen species-mediated signaling pathways in human gastric carcinoma and suppresses tumor growth in nude mice. Arch Toxicol. 2017 Oct;91(10):3341-3364. doi: 10.1007/s00204-017-1967-0. Epub 2017 Apr 3. PMID: 28374157.

In vitro protocol:

In vivo protocol:

1. Hseu YC, Chiang YC, Vudhya Gowrisankar Y, Lin KY, Huang ST, Shrestha S, Chang GR, Yang HL. The In Vitro and In Vivo Anticancer Properties of Chalcone Flavokawain B through Induction of ROS-Mediated Apoptotic and Autophagic Cell Death in Human Melanoma Cells. Cancers (Basel). 2020 Oct 12;12(10):2936. doi: 10.3390/cancers12102936. Erratum in: Cancers (Basel). 2021 Jan 15;13(2): PMID: 33053749; PMCID: PMC7600613. 2. Chang CT, Hseu YC, Thiyagarajan V, Lin KY, Way TD, Korivi M, Liao JW, Yang HL. Chalcone flavokawain B induces autophagic-cell death via reactive oxygen species-mediated signaling pathways in human gastric carcinoma and suppresses tumor growth in nude mice. Arch Toxicol. 2017 Oct;91(10):3341-3364. doi: 10.1007/s00204-017-1967-0. Epub 2017 Apr 3. PMID: 28374157.

1: Malami I, Muhammad A, Etti IC, Waziri PM, Alhassan AM. An in silico approach in predicting the possible mechanism involving restoration of wild-type p53 functions by small molecular weight compounds in tumor cells expressing R273H mutant p53. EXCLI J. 2017 Dec 8;16:1276-1287. doi: 10.17179/excli2017-299. eCollection 2017. PubMed PMID: 29333130; PubMed Central PMCID: PMC5763090. 2: Karimi-Sales E, Mohaddes G, Alipour MR. Chalcones as putative hepatoprotective agents: Preclinical evidence and molecular mechanisms. Pharmacol Res. 2017 Nov 23. pii: S1043-6618(17)31077-0. doi: 10.1016/j.phrs.2017.11.022. [Epub ahead of print] Review. PubMed PMID: 29175112. 3: Rossette MC, Moraes DC, Sacramento EK, Romano-Silva MA, Carvalho JL, Gomes DA, Caldas H, Friedman E, Bastos-Rodrigues L, De Marco L. The In Vitro and In Vivo Antiangiogenic Effects of Flavokawain B. Phytother Res. 2017 Oct;31(10):1607-1613. doi: 10.1002/ptr.5891. Epub 2017 Aug 17. PubMed PMID: 28816367. 4: Chang CT, Hseu YC, Thiyagarajan V, Lin KY, Way TD, Korivi M, Liao JW, Yang HL. Chalcone flavokawain B induces autophagic-cell death via reactive oxygen species-mediated signaling pathways in human gastric carcinoma and suppresses tumor growth in nude mice. Arch Toxicol. 2017 Oct;91(10):3341-3364. doi: 10.1007/s00204-017-1967-0. Epub 2017 Apr 3. PubMed PMID: 28374157. 5: Malami I, Abdul AB, Abdullah R, Kassim NK, Rosli R, Yeap SK, Waziri P, Etti IC, Bello MB. Correction: Crude Extracts, Flavokawain B and Alpinetin Compounds from the Rhizome of Alpinia mutica Induce Cell Death via UCK2 Enzyme Inhibition and in Turn Reduce 18S rRNA Biosynthesis in HT-29 Cells. PLoS One. 2017 Mar 7;12(3):e0173651. doi: 10.1371/journal.pone.0173651. eCollection 2017. PubMed PMID: 28267789; PubMed Central PMCID: PMC5340395. 6: Thieury C, Lebouvier N, Le Guével R, Barguil Y, Herbette G, Antheaume C, Hnawia E, Asakawa Y, Nour M, Guillaudeux T. Mechanisms of action and structure-activity relationships of cytotoxic flavokawain derivatives. Bioorg Med Chem. 2017 Mar 15;25(6):1817-1829. doi: 10.1016/j.bmc.2017.01.049. Epub 2017 Feb 6. PubMed PMID: 28214231. 7: Malami I, Abdul AB, Abdullah R, Kassim NK, Rosli R, Yeap SK, Waziri P, Etti IC, Bello MB. Crude Extracts, Flavokawain B and Alpinetin Compounds from the Rhizome of Alpinia mutica Induce Cell Death via UCK2 Enzyme Inhibition and in Turn Reduce 18S rRNA Biosynthesis in HT-29 Cells. PLoS One. 2017 Jan 19;12(1):e0170233. doi: 10.1371/journal.pone.0170233. eCollection 2017. Erratum in: PLoS One. 2017 Mar 7;12 (3):e0173651. PubMed PMID: 28103302; PubMed Central PMCID: PMC5245823. 8: Yeap SK, Abu N, Akthar N, Ho WY, Ky H, Tan SW, Alitheen NB, Kamarul T. Gene Expression Analysis Reveals the Concurrent Activation of Proapoptotic and Antioxidant-Defensive Mechanisms in Flavokawain B-Treated Cervical Cancer HeLa Cells. Integr Cancer Ther. 2017 Sep;16(3):373-384. doi: 10.1177/1534735416660383. Epub 2016 Jul 24. PubMed PMID: 27458249; PubMed Central PMCID: PMC5759947. 9: Rodrigues DF, Maniscalco DA, Silva FA, Chiari BG, Castelli MV, Isaac VL, Cicarelli RM, López SN. Trypanocidal Activity of Flavokawin B, a Component of Polygonum ferrugineum Wedd. Planta Med. 2017 Feb;83(3-04):239-244. doi: 10.1055/s-0042-112031. Epub 2016 Jul 21. PubMed PMID: 27442262. 10: Malami I, Abdul AB, Abdullah R, Bt Kassim NK, Waziri P, Christopher Etti I. In Silico Discovery of Potential Uridine-Cytidine Kinase 2 Inhibitors from the Rhizome of Alpinia mutica. Molecules. 2016 Apr 8;21(4):417. doi: 10.3390/molecules21040417. PubMed PMID: 27070566. 11: Abu N, Akhtar MN, Yeap SK, Lim KL, Ho WY, Abdullah MP, Ho CL, Omar AR, Ismail J, Alitheen NB. Flavokawain B induced cytotoxicity in two breast cancer cell lines, MCF-7 and MDA-MB231 and inhibited the metastatic potential of MDA-MB231 via the regulation of several tyrosine kinases In vitro. BMC Complement Altern Med. 2016 Feb 27;16:86. doi: 10.1186/s12906-016-1046-8. PubMed PMID: 26922065; PubMed Central PMCID: PMC4769841. 12: Pinner KD, Wales CT, Gristock RA, Vo HT, So N, Jacobs AT. Flavokawains A and B from kava (Piper methysticum) activate heat shock and antioxidant responses and protect against hydrogen peroxide-induced cell death in HepG2 hepatocytes. Pharm Biol. 2016 Sep;54(9):1503-12. doi: 10.3109/13880209.2015.1107104. Epub 2016 Jan 20. PubMed PMID: 26789234; PubMed Central PMCID: PMC5040346. 13: Abu N, Mohameda NE, Tangarajoo N, Yeap SK, Akhtar MN, Abdullah MP, Omar AR, Alitheen NB. In vitro Toxicity and in vivo Immunomodulatory Effects of Flavokawain A and Flavokawain B in Balb/C Mice. Nat Prod Commun. 2015 Jul;10(7):1199-202. PubMed PMID: 26411010. 14: Liu H, Fan H, Gao X, Huang X, Liu X, Liu L, Zhou C, Tang J, Wang Q, Liu W. Design, synthesis and preliminary structure-activity relationship investigation of nitrogen-containing chalcone derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors: a further study based on Flavokawain B Mannich base derivatives. J Enzyme Inhib Med Chem. 2016 Aug;31(4):580-9. doi: 10.3109/14756366.2015.1050009. Epub 2015 Jul 17. PubMed PMID: 26186269. 15: Zenger K, Agnolet S, Schneider B, Kraus B. Biotransformation of Flavokawains A, B, and C, Chalcones from Kava (Piper methysticum), by Human Liver Microsomes. J Agric Food Chem. 2015 Jul 22;63(28):6376-85. doi: 10.1021/acs.jafc.5b01858. Epub 2015 Jul 10. PubMed PMID: 26123050. 16: Abu N, Mohamed NE, Yeap SK, Lim KL, Akhtar MN, Zulfadli AJ, Kee BB, Abdullah MP, Omar AR, Alitheen NB. In vivo antitumor and antimetastatic effects of flavokawain B in 4T1 breast cancer cell-challenged mice. Drug Des Devel Ther. 2015 Mar 6;9:1401-17. doi: 10.2147/DDDT.S67976. eCollection 2015. PubMed PMID: 25834398; PubMed Central PMCID: PMC4358690. 17: Tang YL, Huang LB, Tian Y, Wang LN, Zhang XL, Ke ZY, Deng WG, Luo XQ. Flavokawain B inhibits the growth of acute lymphoblastic leukemia cells via p53 and caspase-dependent mechanisms. Leuk Lymphoma. 2015;56(8):2398-407. doi: 10.3109/10428194.2014.976819. Epub 2015 Feb 23. PubMed PMID: 25641429. 18: Jeong HJ, Lee CS, Choi J, Hong YD, Shin SS, Park JS, Lee JH, Lee S, Yoon KD, Ko J. Flavokawains B and C, melanogenesis inhibitors, isolated from the root of Piper methysticum and synthesis of analogs. Bioorg Med Chem Lett. 2015 Feb 15;25(4):799-802. doi: 10.1016/j.bmcl.2014.12.082. Epub 2015 Jan 3. PubMed PMID: 25597012. 19: Liu HR, Huang XQ, Lou DH, Liu XJ, Liu WK, Wang QA. Synthesis and acetylcholinesterase inhibitory activity of Mannich base derivatives flavokawain B. Bioorg Med Chem Lett. 2014 Oct 1;24(19):4749-4753. doi: 10.1016/j.bmcl.2014.07.087. Epub 2014 Aug 27. PubMed PMID: 25205193. 20: Narayanapillai SC, Leitzman P, O'Sullivan MG, Xing C. Flavokawains a and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 mice. Chem Res Toxicol. 2014 Oct 20;27(10):1871-6. doi: 10.1021/tx5003194. Epub 2014 Sep 12. PubMed PMID: 25185080; PubMed Central PMCID: PMC4203398.