FL118 | CAS#151636-76-9 | survivin inhibitor

MedKoo Cat#: 527474 | Name: FL118

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Description:

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

FL118 is an inhibitor of human survivin expression, activating tumor suppressor p53 as a novel MOA in p53 wild-type cancer cells. FL118 strongly binds to dephosphorylates and degrades the DDX5 oncoprotein via the proteasome degradation pathway without decreasing DDX5 mRNA. FL118 exhibits high efficacy to eliminate human PDAC and CRC tumours that have a high expression of DDX5. FL118 may act as a 'molecular glue degrader' to directly glue DDX5 and ubiquitination regulators together to degrade DDX5.

Chemical Structure

FL118

CAS#151636-76-9

Theoretical Analysis

MedKoo Cat#: 527474

Name: FL118

CAS#: 151636-76-9

Chemical Formula: C21H16N2O6

Exact Mass: 392.1008

Molecular Weight: 392.37

Elemental Analysis: C, 64.28; H, 4.11; N, 7.14; O, 24.47

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 750.00	2 Weeks
10mg	USD 1,250.00	2 Weeks

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Related CAS #

No Data

Synonym

FL118; FL 118; FL-118

IUPAC/Chemical Name

(4R)-4-Ethyl-4-hydroxy-8,9-methylenedioxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione

InChi Key

RPFYDENHBPRCTN-OAQYLSRUSA-N

InChi Code

InChI=1S/C21H16N2O6/c1-2-21(26)13-5-15-18-11(7-23(15)19(24)12(13)8-27-20(21)25)3-10-4-16-17(29-9-28-16)6-14(10)22-18/h3-6,26H,2,7-9H2,1H3/t21-/m1/s1

SMILES Code

O=C1[C@@](O)(CC)C2=C(CO1)C(N3CC4=CC5=CC6=C(OCO6)C=C5N=C4C3=C2)=O

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

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 392.37 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

1: Ling X, Wu W, Aljahdali IAM, Liao J, Santha S, Fountzilas C, Boland PM, Li F. FL118, acting as a 'molecular glue degrader', binds to dephosphorylates and degrades the oncoprotein DDX5 (p68) to control c-Myc, survivin and mutant Kras against colorectal and pancreatic cancer with high efficacy. Clin Transl Med. 2022 May;12(5):e881. doi: 10.1002/ctm2.881. PMID: 35604033; PMCID: PMC9126027. 2: Zhou Y, Hu W, Zhang X, Wang Y, Zhuang W, Li F, Li Q. Cellular Uptake and Transport Characteristics of FL118 Derivatives in Caco-2 Cell Monolayers. Chem Pharm Bull (Tokyo). 2021;69(11):1054-1060. doi: 10.1248/cpb.c21-00467. PMID: 34719586. 3: Thangaiyan R, Aljahdali IA, Lent-Moore KY, Liao J, Ling X, Li F. Kras mutation subtypes distinctly affect colorectal cancer cell sensitivity to FL118, a novel inhibitor of survivin, Mcl-1, XIAP, cIAP2 and MdmX. Am J Transl Res. 2021 Jul 15;13(7):7458-7474. PMID: 34377229; PMCID: PMC8340187. 4: Yar Saglam AS, Kayhan H, Alp E, Onen HI. Resveratrol enhances the sensitivity of FL118 in triple-negative breast cancer cell lines via suppressing epithelial to mesenchymal transition. Mol Biol Rep. 2021 Jan;48(1):475-489. doi: 10.1007/s11033-020-06078-y. Epub 2021 Jan 3. PMID: 33389483. 5: Santha S, Ling X, Aljahdali IAM, Rasam SS, Wang X, Liao J, Wang J, Fountzilas C, Li Q, Qu J, Li F. Mutant Kras as a Biomarker Plays a Favorable Role in FL118-Induced Apoptosis, Reactive Oxygen Species (ROS) Production and Modulation of Survivin, Mcl-1 and XIAP in Human Bladder Cancer. Cancers (Basel). 2020 Nov 18;12(11):3413. doi: 10.3390/cancers12113413. PMID: 33217967; PMCID: PMC7698790. 6: Tang Z, Ji L, Han M, Xie J, Zhong F, Zhang X, Su Q, Yang Z, Liu Z, Gao H, Jiang G. Pyroptosis is involved in the inhibitory effect of FL118 on growth and metastasis in colorectal cancer. Life Sci. 2020 Sep 15;257:118065. doi: 10.1016/j.lfs.2020.118065. Epub 2020 Jul 11. PMID: 32659366. 7: Feng K, Zhang J, Zhang Y, Jiang T, Lv Z, Yu M. Simultaneous determination of FL118 and W34 in rat Blood by LC-MS/MS: Application to pharmacokinetic studies. Biomed Chromatogr. 2020 Nov;34(11):e4944. doi: 10.1002/bmc.4944. Epub 2020 Jul 21. PMID: 32639034. 8: Lin X, Gao M, Zhang A, Tong J, Zhang X, Su Q, Yang Z, Gao H, Jiang G. Retraction notice to "FL118 inhibits viability and induces apoptosis of colorectal cancer cells via inactivating the CIP2A/PP2A axis" [Life Sci. 239 (2019) 117074]. Life Sci. 2020 Sep 1;256:118023. doi: 10.1016/j.lfs.2020.118023. Epub 2020 Jul 2. PMID: 32624224. 9: Lin X, Gao M, Zhang A, Tong J, Zhang X, Su Q, Yang Z, Gao H, Jiang G. FL118 inhibits viability and induces apoptosis of colorectal cancer cells via inactivating the CIP2A/PP2A axis. Life Sci. 2019 Dec 15;239:117074. doi: 10.1016/j.lfs.2019.117074. Epub 2019 Nov 18. Retraction in: Life Sci. 2020 Sep 1;256:118023. PMID: 31751585. 10: Zhou L, Weng Q, Zheng Y, Zhou Y, Li Q, Li F. Uptake and efflux of FL118 and two FL118 derivatives in 3D cell model. Cytotechnology. 2019 Jul 12;71(4):785-795. doi: 10.1007/s10616-019-00322-5. Epub ahead of print. PMID: 31309350; PMCID: PMC6663949. 11: Holthof LC, van der Horst HJ, van Hal-van Veen SE, Ruiter RWJ, Li F, Buijze M, Andersen MN, Yuan H, de Bruijn J, van de Donk NWCJ, Lokhorst HM, Zweegman S, Groen RWJ, Mutis T. Preclinical evidence for an effective therapeutic activity of FL118, a novel survivin inhibitor, in patients with relapsed/refractory multiple myeloma. Haematologica. 2020 Jan 31;105(2):e80-e83. doi: 10.3324/haematol.2018.213314. PMID: 31123033; PMCID: PMC7012462. 12: Weng Q, Zhou L, Xia L, Zheng Y, Zhang X, Li F, Li Q. In vitro evaluation of FL118 and 9-Q20 cytotoxicity and cellular uptake in 2D and 3D different cell models. Cancer Chemother Pharmacol. 2019 Sep;84(3):527-537. doi: 10.1007/s00280-019-03846-x. Epub 2019 Apr 27. PMID: 31030236. 13: Rabi T, Li F. Multiple mechanisms involved in a low concentration of FL118 enhancement of AMR-MeOAc to induce pancreatic cancer cell apoptosis and growth inhibition. Am J Cancer Res. 2018 Nov 1;8(11):2267-2283. PMID: 30555743; PMCID: PMC6291652. 14: Ling X, Wu W, Fan C, Xu C, Liao J, Rich LJ, Huang RY, Repasky EA, Wang X, Li F. An ABCG2 non-substrate anticancer agent FL118 targets drug-resistant cancer stem-like cells and overcomes treatment resistance of human pancreatic cancer. J Exp Clin Cancer Res. 2018 Oct 3;37(1):240. doi: 10.1186/s13046-018-0899-8. PMID: 30285798; PMCID: PMC6169080. 15: Yang Z, Ji L, Jiang G, Liu R, Liu Z, Yang Y, Ma Q, Zhao H. FL118, a novel camptothecin analogue, suppressed migration and invasion of human breast cancer cells by inhibiting epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway. Biosci Trends. 2018;12(1):40-46. doi: 10.5582/bst.2017.01288. PMID: 29553100. 16: Wang J, Liu Z, Zhang D, Liu R, Lin Q, Liu J, Yang Z, Ma Q, Sun D, Zhou X, Jiang G. FL118, a novel survivin inhibitor, wins the battle against drug- resistant and metastatic lung cancers through inhibition of cancer stem cell- like properties. Am J Transl Res. 2017 Aug 15;9(8):3676-3686. PMID: 28861158; PMCID: PMC5575181. 17: Li F, Ling X, Harris DL, Liao J, Wang Y, Westover D, Jiang G, Xu B, Boland PM, Jin C. Topoisomerase I (Top1): a major target of FL118 for its antitumor efficacy or mainly involved in its side effects of hematopoietic toxicity? Am J Cancer Res. 2017 Feb 1;7(2):370-382. PMID: 28337384; PMCID: PMC5336509. 18: Ling X, Liu X, Zhong K, Smith N, Prey J, Li F. FL118, a novel camptothecin analogue, overcomes irinotecan and topotecan resistance in human tumor xenograft models. Am J Transl Res. 2015 Oct 15;7(10):1765-81. PMID: 26692923; PMCID: PMC4656756. 19: Westover D, Ling X, Lam H, Welch J, Jin C, Gongora C, Del Rio M, Wani M, Li F. FL118, a novel camptothecin derivative, is insensitive to ABCG2 expression and shows improved efficacy in comparison with irinotecan in colon and lung cancer models with ABCG2-induced resistance. Mol Cancer. 2015 Apr 28;14:92. doi: 10.1186/s12943-015-0362-9. PMID: 25928015; PMCID: PMC4427926. 20: Ling X, Xu C, Fan C, Zhong K, Li F, Wang X. FL118 induces p53-dependent senescence in colorectal cancer cells by promoting degradation of MdmX. Cancer Res. 2014 Dec 15;74(24):7487-97. doi: 10.1158/0008-5472.CAN-14-0683. PMID: 25512388; PMCID: PMC4448973.