Fascaplysin chloride

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

MedKoo CAT#: 329606

CAS#: 14719-57-2

Description: Fascaplysin is an inhibitor of cyclin D kinase 4/ cyclin D1 (IC50 = 0.35 μM). Fascaplysin induces caspase mediated crosstalk between apoptosis and autophagy through the inhibition of PI3K/AKT/mTOR signaling cascade in human leukemia HL-60 cells.


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Fascaplysine is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 329606
Name: Fascaplysin chloride
CAS#: 14719-57-2
Chemical Formula: C18H11ClN2O
Exact Mass:
Molecular Weight: 306.749
Elemental Analysis: C, 70.48; H, 3.61; Cl, 11.56; N, 9.13; O, 5.22


Synonym: Fascaplysin; Fascaplysin chloride; NSC 622398; NSC622398; NSC-622398.

IUPAC/Chemical Name: 12,13-dihydro-13-oxo-pyrido[1,2-a:3,4-b']diindol-5-ium, monochloride

InChi Key: PWUOOJVYZQILBG-UHFFFAOYSA-N

InChi Code: InChI=1S/C18H10N2O.ClH/c21-18-13-6-2-4-8-15(13)20-10-9-12-11-5-1-3-7-14(11)19-16(12)17(18)20;/h1-10H;1H

SMILES Code: O=C1C2=C3NC4=C(C=CC=C4)C3=CC=[N+]2C5=C1C=CC=C5.[Cl-]


Technical Data

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).

Harmonized System Code:
293490


References

1: Mischitelli M, Jemaà M, Almasry M, Faggio C, Lang F. Triggering of Suicidal Erythrocyte Death by Fascaplysin. Cell Physiol Biochem. 2016;39(4):1638-47. doi: 10.1159/000447865. PubMed PMID: 27626793.

2: Manda S, Sharma S, Wani A, Joshi P, Kumar V, Guru SK, Bharate SS, Bhushan S, Vishwakarma RA, Kumar A, Bharate SB. Discovery of a marine-derived bis-indole alkaloid fascaplysin, as a new class of potent P-glycoprotein inducer and establishment of its structure-activity relationship. Eur J Med Chem. 2016 Jan 1;107:1-11. doi: 10.1016/j.ejmech.2015.10.049. PubMed PMID: 26560048.

3: Ampofo E, Später T, Müller I, Eichler H, Menger MD, Laschke MW. The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic Activity. Mar Drugs. 2015 Nov 9;13(11):6774-91. doi: 10.3390/md13116774. PubMed PMID: 26569265; PubMed Central PMCID: PMC4663553.

4: Mahgoub T, Eustace AJ, Collins DM, Walsh N, O'Donovan N, Crown J. Kinase inhibitor screening identifies CDK4 as a potential therapeutic target for melanoma. Int J Oncol. 2015 Sep;47(3):900-8. doi: 10.3892/ijo.2015.3097. PubMed PMID: 26201960; PubMed Central PMCID: PMC4532220.

5: Kumar S, Guru SK, Pathania AS, Manda S, Kumar A, Bharate SB, Vishwakarma RA, Malik F, Bhushan S. Fascaplysin induces caspase mediated crosstalk between apoptosis and autophagy through the inhibition of PI3K/AKT/mTOR signaling cascade in human leukemia HL-60 cells. J Cell Biochem. 2015 Jun;116(6):985-97. doi: 10.1002/jcb.25053. PubMed PMID: 25561006.

6: Mahale S, Bharate SB, Manda S, Joshi P, Bharate SS, Jenkins PR, Vishwakarma RA, Chaudhuri B. Biphenyl-4-carboxylic acid [2-(1H-indol-3-yl)-ethyl]-methylamide (CA224), a nonplanar analogue of fascaplysin, inhibits Cdk4 and tubulin polymerization: evaluation of in vitro and in vivo anticancer activity. J Med Chem. 2014 Nov 26;57(22):9658-72. doi: 10.1021/jm5014743. PubMed PMID: 25368960.

7: Hamilton G. Cytotoxic effects of fascaplysin against small cell lung cancer cell lines. Mar Drugs. 2014 Mar 7;12(3):1377-89. doi: 10.3390/md12031377. PubMed PMID: 24608973; PubMed Central PMCID: PMC3967216.

8: Zhu YP, Liu MC, Cai Q, Jia FC, Wu AX. A cascade coupling strategy for one-pot total synthesis of β-carboline and isoquinoline-containing natural products and derivatives. Chemistry. 2013 Jul 29;19(31):10132-7. doi: 10.1002/chem.201301734. PubMed PMID: 23788489.

9: Bharate SB, Sawant SD, Singh PP, Vishwakarma RA. Kinase inhibitors of marine origin. Chem Rev. 2013 Aug 14;113(8):6761-815. doi: 10.1021/cr300410v. Review. PubMed PMID: 23679846.

10: Bharate SB, Manda S, Mupparapu N, Battini N, Vishwakarma RA. Chemistry and biology of fascaplysin, a potent marine-derived CDK-4 inhibitor. Mini Rev Med Chem. 2012 Jun;12(7):650-64. Review. PubMed PMID: 22512549.

11: Shafiq MI, Steinbrecher T, Schmid R. Fascaplysin as a specific inhibitor for CDK4: insights from molecular modelling. PLoS One. 2012;7(8):e42612. doi: 10.1371/journal.pone.0042612. PubMed PMID: 22905154; PubMed Central PMCID: PMC3419161.

12: Lu Z, Ding Y, Li XC, Djigbenou DR, Grimberg BT, Ferreira D, Ireland CM, Van Wagoner RM. 3-bromohomofascaplysin A, a fascaplysin analogue from a Fijian Didemnum sp. ascidian. Bioorg Med Chem. 2011 Nov 15;19(22):6604-7. doi: 10.1016/j.bmc.2011.05.046. PubMed PMID: 21696970; PubMed Central PMCID: PMC3205246.

13: Yan X, Chen H, Lu X, Wang F, Xu W, Jin H, Zhu P. Fascaplysin exert anti-tumor effects through apoptotic and anti-angiogenesis pathways in sarcoma mice model. Eur J Pharm Sci. 2011 Jul 17;43(4):251-9. doi: 10.1016/j.ejps.2011.04.018. PubMed PMID: 21569843.

14: Zheng YL, Lu XL, Lin J, Chen HM, Yan XJ, Wang F, Xu WF. Direct effects of fascaplysin on human umbilical vein endothelial cells attributing the anti-angiogenesis activity. Biomed Pharmacother. 2010 Oct;64(8):527-33. doi: 10.1016/j.biopha.2009.04.046. PubMed PMID: 19932581.

15: Waldmann H, Eberhardt L, Wittstein K, Kumar K. Silver catalyzed cascade synthesis of alkaloid ring systems: concise total synthesis of fascaplysin, homofascaplysin C and analogues. Chem Commun (Camb). 2010 Jul 7;46(25):4622-4. doi: 10.1039/c001350a. PubMed PMID: 20386812.

16: Lu XL, Zheng YL, Chen HM, Yan XJ, Wang F, Xu WF. [Anti-proliferation of human cervical cancer HeLa cell line by fascaplysin through apoptosis induction]. Yao Xue Xue Bao. 2009 Sep;44(9):980-6. Chinese. PubMed PMID: 20055172.

17: Aubry C, Wilson AJ, Emmerson D, Murphy E, Chan YY, Dickens MP, García MD, Jenkins PR, Mahale S, Chaudhuri B. Fascaplysin-inspired diindolyls as selective inhibitors of CDK4/cyclin D1. Bioorg Med Chem. 2009 Aug 15;17(16):6073-84. doi: 10.1016/j.bmc.2009.06.070. PubMed PMID: 19632122.

18: Liu N, Fang H, Li Y, Xu W. Recent research in selective cyclin-dependent kinase 4 inhibitors for anti-cancer treatment. Curr Med Chem. 2009;16(36):4869-88. Review. PubMed PMID: 19929781.

19: Lin J, Yan XJ, Chen HM. Fascaplysin, a selective CDK4 inhibitor, exhibit anti-angiogenic activity in vitro and in vivo. Cancer Chemother Pharmacol. 2007 Mar;59(4):439-45. PubMed PMID: 16816972.

20: García MD, Wilson AJ, Emmerson DP, Jenkins PR, Mahale S, Chaudhuri B. Synthesis, crystal structure and biological activity of beta-carboline based selective CDK4-cyclin D1 inhibitors. Org Biomol Chem. 2006 Dec 21;4(24):4478-84. PubMed PMID: 17268643.