YK-4-279
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MedKoo CAT#: 406807

CAS#: 1037184-44-3

Description: YK-4-279 is a ETV1 inhibitor, which inhibitor protein-protein interactions between ES-FLI1 and RHA.YK-4-279 effectively antagonizes EWS-FLI1 induced leukemia in a transgenic mouse model. YK-4-279 demonstrates specificity in targeting the oncogene EWS-FLI1. YK-4-279, prevents prostate cancer growth and metastasis in a mouse xenograft model.


Chemical Structure

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YK-4-279
CAS# 1037184-44-3

Theoretical Analysis

MedKoo Cat#: 406807
Name: YK-4-279
CAS#: 1037184-44-3
Chemical Formula: C17H13Cl2NO
Exact Mass: 365.0222
Molecular Weight: 366.194
Elemental Analysis: C, 55.76; H, 3.58; Cl, 19.36; N, 3.83; O, 17.48

Price and Availability

Size Price Availability Quantity
10.0mg USD 150.0 Ready to ship
25.0mg USD 250.0 Ready to ship
50.0mg USD 450.0 Ready to ship
100.0mg USD 750.0 Ready to ship
200.0mg USD 1250.0 Ready to ship
500.0mg USD 2650.0 Ready to ship
1.0g USD 3850.0 Ready to ship
2.0g USD 6250.0 Ready to ship
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Synonym: YK-4-279; YK4-279; YK 4-279; YK-4279; YK4279; YK 4279.

IUPAC/Chemical Name: 4,7-dichloro-1,3-dihydro-3-hydroxy-3-[2-(4-methoxyphenyl)-2-oxoethyl]-2H-indole-2-one

InChi Key: HLXSCTYHLQHQDJ-UHFFFAOYSA-N

InChi Code: InChI=1S/C17H13Cl2NO4/c1-24-10-4-2-9(3-5-10)13(21)8-17(23)14-11(18)6-7-12(19)15(14)20-16(17)22/h2-7,23H,8H2,1H3,(H,20,22)

SMILES Code: O=C1NC2=C(C(Cl)=CC=C2Cl)C1(O)CC(C3=CC=C(OC)C=C3)=O

Appearance: White 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

Biological target: YK-4-279 is a potent inhibitor of EWS-FLI1 binding to RNA helicase A (RHA).
In vitro activity: The ability of YK-4-279 to inhibit biological functions of ERG and ETV1 proteins in prostate cancer was tested. YK-4-279 inhibited ERG and ETV1 mediated transcriptional activity in a luciferase assay. YK-4-279 also decreased ERG and ETV1 downstream target mRNA and protein expression in ETV1-fusion positive LNCaP and ERG fusion positive VCaP cells. YK-4-279 reduced the motility of LNCaP cells in a scratch assay and the invasive phenotype of both LNCaP and VCaP cells in a HUVEC invasion assay. Fusion-negative PC3 cells were unresponsive to YK-4-279. SiRNA mediated ERG knockdown in VCaP cells resulted in a loss of drug responsiveness. Concurrently, transient ERG expression in PC-3 cells resulted in increased invasive potential, which was reduced by YK-4-279. Reference: PLoS One. 2011 Apr 29;6(4):e19343. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21559405/
In vivo activity: CID-beige mice were subcutaneously implanted with fusion-positive LNCaP-luc-M6 and fusion-negative PC-3M-luc-C6 tumors. Animals were treated with YK-4-279, and its effects on primary tumor growth and lung metastasis were evaluated. YK-4-279 treatment resulted in decreased growth of the primary tumor only in LNCaP-luc-M6 cohort. When primary tumors were grown to comparable sizes, YK-4-279 inhibited tumor metastasis to the lungs. Expression of ETV1 target genes MMP7, FKBP10 and GLYATL2 were reduced in YK-4-279 treated animals. ETS fusion-negative PC-3M-luc-C6 xenografts were unresponsive to the compound. Furthermore, YK-4-279 is a chiral molecule that exists as a racemic mixture of R and S enantiomers. It was established that (S)-YK-4-279 is the active enantiomer in prostate cancer cells. Reference: PLoS One. 2014 Dec 5;9(12):e114260. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25479232/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 36.62 100.0
Ethanol 25.0 68.27

Preparing Stock Solutions

The following data is based on the product molecular weight 366.194 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.

Recalculate based on batch purity %
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
In vitro protocol: 1. Rahim S, Beauchamp EM, Kong Y, Brown ML, Toretsky JA, Üren A. YK-4-279 inhibits ERG and ETV1 mediated prostate cancer cell invasion. PLoS One. 2011 Apr 29;6(4):e19343. doi: 10.1371/journal.pone.0019343. PMID: 21559405; PMCID: PMC3084826. 2. Erkizan HV, Kong Y, Merchant M, Schlottmann S, Barber-Rotenberg JS, Yuan L, Abaan OD, Chou TH, Dakshanamurthy S, Brown ML, Uren A, Toretsky JA. A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing's sarcoma. Nat Med. 2009 Jul;15(7):750-6. doi: 10.1038/nm.1983. Epub 2009 Jul 5. PMID: 19584866; PMCID: PMC2777681.
In vivo protocol: 1. Rahim S, Minas T, Hong SH, Justvig S, Çelik H, Kont YS, Han J, Kallarakal AT, Kong Y, Rudek MA, Brown ML, Kallakury B, Toretsky JA, Üren A. A small molecule inhibitor of ETV1, YK-4-279, prevents prostate cancer growth and metastasis in a mouse xenograft model. PLoS One. 2014 Dec 5;9(12):e114260. doi: 10.1371/journal.pone.0114260. PMID: 25479232; PMCID: PMC4257561. 2. Erkizan HV, Kong Y, Merchant M, Schlottmann S, Barber-Rotenberg JS, Yuan L, Abaan OD, Chou TH, Dakshanamurthy S, Brown ML, Uren A, Toretsky JA. A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing's sarcoma. Nat Med. 2009 Jul;15(7):750-6. doi: 10.1038/nm.1983. Epub 2009 Jul 5. PMID: 19584866; PMCID: PMC2777681.

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1: Minas TZ, Han J, Javaheri T, Hong SH, Schlederer M, Saygideğer-Kont Y, Çelik H, Mueller KM, Temel I, Özdemirli M, Kovar H, Erkizan HV, Toretsky J, Kenner L, Moriggl R, Üren A. YK-4-279 effectively antagonizes EWS-FLI1 induced leukemia in a transgenic mouse model. Oncotarget. 2015 Nov 10;6(35):37678-94. doi: 10.18632/oncotarget.5520. PubMed PMID: 26462019; PubMed Central PMCID: PMC4741957.

2: Lamhamedi-Cherradi SE, Menegaz BA, Ramamoorthy V, Aiyer RA, Maywald RL, Buford AS, Doolittle DK, Culotta KS, O'Dorisio JE, Ludwig JA. An Oral Formulation of YK-4-279: Preclinical Efficacy and Acquired Resistance Patterns in Ewing Sarcoma. Mol Cancer Ther. 2015 Jul;14(7):1591-604. doi: 10.1158/1535-7163.MCT-14-0334. Epub 2015 May 11. PubMed PMID: 25964201.

3: Selvanathan SP, Graham GT, Erkizan HV, Dirksen U, Natarajan TG, Dakic A, Yu S, Liu X, Paulsen MT, Ljungman ME, Wu CH, Lawlor ER, Üren A, Toretsky JA. Oncogenic fusion protein EWS-FLI1 is a network hub that regulates alternative splicing. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):E1307-16. doi: 10.1073/pnas.1500536112. Epub 2015 Mar 3. PubMed PMID: 25737553; PubMed Central PMCID: PMC4371969.

4: Erkizan HV, Schneider JA, Sajwan K, Graham GT, Griffin B, Chasovskikh S, Youbi SE, Kallarakal A, Chruszcz M, Padmanabhan R, Casey JL, Üren A, Toretsky JA. RNA helicase A activity is inhibited by oncogenic transcription factor EWS-FLI1. Nucleic Acids Res. 2015 Jan;43(2):1069-80. doi: 10.1093/nar/gku1328. Epub 2015 Jan 6. PubMed PMID: 25564528; PubMed Central PMCID: PMC4333382.

5: Rahim S, Minas T, Hong SH, Justvig S, Çelik H, Kont YS, Han J, Kallarakal AT, Kong Y, Rudek MA, Brown ML, Kallakury B, Toretsky JA, Üren A. A small molecule inhibitor of ETV1, YK-4-279, prevents prostate cancer growth and metastasis in a mouse xenograft model. PLoS One. 2014 Dec 5;9(12):e114260. doi: 10.1371/journal.pone.0114260. eCollection 2014. PubMed PMID: 25479232; PubMed Central PMCID: PMC4257561.

6: Tosso PN, Kong Y, Scher L, Cummins R, Schneider J, Rahim S, Holman KT, Toretsky J, Wang K, Üren A, Brown ML. Synthesis and structure-activity relationship studies of small molecule disruptors of EWS-FLI1 interactions in Ewing's sarcoma. J Med Chem. 2014 Dec 26;57(24):10290-303. doi: 10.1021/jm501372p. Epub 2014 Dec 12. PubMed PMID: 25432018; PubMed Central PMCID: PMC4281097.

7: Kovar H. Blocking the road, stopping the engine or killing the driver? Advances in targeting EWS/FLI-1 fusion in Ewing sarcoma as novel therapy. Expert Opin Ther Targets. 2014 Nov;18(11):1315-28. doi: 10.1517/14728222.2014.947963. Epub 2014 Aug 27. Review. PubMed PMID: 25162919.

8: van der Ent W, Jochemsen AG, Teunisse AF, Krens SF, Szuhai K, Spaink HP, Hogendoorn PC, Snaar-Jagalska BE. Ewing sarcoma inhibition by disruption of EWSR1-FLI1 transcriptional activity and reactivation of p53. J Pathol. 2014 Aug;233(4):415-24. doi: 10.1002/path.4378. Epub 2014 Jun 27. PubMed PMID: 24974828.

9: Hong SH, Youbi SE, Hong SP, Kallakury B, Monroe P, Erkizan HV, Barber-Rotenberg JS, Houghton P, Üren A, Toretsky JA. Pharmacokinetic modeling optimizes inhibition of the 'undruggable' EWS-FLI1 transcription factor in Ewing Sarcoma. Oncotarget. 2014 Jan 30;5(2):338-50. PubMed PMID: 24481407; PubMed Central PMCID: PMC3964211.

10: Barber-Rotenberg JS, Selvanathan SP, Kong Y, Erkizan HV, Snyder TM, Hong SP, Kobs CL, South NL, Summer S, Monroe PJ, Chruszcz M, Dobrev V, Tosso PN, Scher LJ, Minor W, Brown ML, Metallo SJ, Üren A, Toretsky JA. Single enantiomer of YK-4-279 demonstrates specificity in targeting the oncogene EWS-FLI1. Oncotarget. 2012 Feb;3(2):172-82. PubMed PMID: 22383402; PubMed Central PMCID: PMC3326647.

11: Rahim S, Beauchamp EM, Kong Y, Brown ML, Toretsky JA, Üren A. YK-4-279 inhibits ERG and ETV1 mediated prostate cancer cell invasion. PLoS One. 2011 Apr 29;6(4):e19343. doi: 10.1371/journal.pone.0019343. PubMed PMID: 21559405; PubMed Central PMCID: PMC3084826.

12: Awad O, Yustein JT, Shah P, Gul N, Katuri V, O'Neill A, Kong Y, Brown ML, Toretsky JA, Loeb DM. High ALDH activity identifies chemotherapy-resistant Ewing's sarcoma stem cells that retain sensitivity to EWS-FLI1 inhibition. PLoS One. 2010 Nov 11;5(11):e13943. doi: 10.1371/journal.pone.0013943. PubMed PMID: 21085683; PubMed Central PMCID: PMC2978678.

13: Erkizan HV, Kong Y, Merchant M, Schlottmann S, Barber-Rotenberg JS, Yuan L, Abaan OD, Chou TH, Dakshanamurthy S, Brown ML, Uren A, Toretsky JA. A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing's sarcoma. Nat Med. 2009 Jul;15(7):750-6. doi: 10.1038/nm.1983. Epub 2009 Jul 5. PubMed PMID: 19584866; PubMed Central PMCID: PMC2777681.

YK-4-279

10.0mg / USD 150.0