Encorafenib
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MedKoo CAT#: 205852

CAS#: 1269440-17-6

Description: Encorafenib, also known as LGX-818, is an orally available Raf kinase inhibitor with potential antineoplastic activity. LGX818 specifically inhibits Raf kinase, a serine/threonine enzyme in the RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) signaling pathway. By inhibiting the activation of the RAF/MEK/ERK signaling pathway, the administration of LGX818 may result in a decrease in proliferation of tumor cells.


Price and Availability

Size
Price

10mg
USD 250
100mg
USD 1250
1g
USD 3750
Size
Price

25mg
USD 450
200mg
USD 1850
2g
USD 5950
Size
Price

50mg
USD 750
500mg
USD 2950
5g
Ask price

Encorafenib, purity > 98%, is in stock. The same day shipping out after order is received. Note: the estimated shipping out time for order > 500mg may be 2 weeks.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 205852
Name: Encorafenib
CAS#: 1269440-17-6
Chemical Formula: C22H27ClFN7O4S
Exact Mass: 539.15178
Molecular Weight: 540.01
Elemental Analysis: C, 48.93; H, 5.04; Cl, 6.57; F, 3.52; N, 18.16; O, 11.85; S, 5.94


Related CAS #: 1269440-17-6   1269440-29-0 (R-isomer of LGX-818)    

Synonym: LGX818; LGX-818; LGX 818; Encorafenib.

IUPAC/Chemical Name: (S)-methyl (1-((4-(3-(5-chloro-2-fluoro-3-(methylsulfonamido)phenyl)-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)propan-2-yl)carbamate.

InChi Key: CMJCXYNUCSMDBY-ZDUSSCGKSA-N

InChi Code: InChI=1S/C22H27ClFN7O4S/c1-12(2)31-11-16(17-6-7-25-21(28-17)26-10-13(3)27-22(32)35-4)20(29-31)15-8-14(23)9-18(19(15)24)30-36(5,33)34/h6-9,11-13,30H,10H2,1-5H3,(H,27,32)(H,25,26,28)/t13-/m0/s1

SMILES Code: O=C(OC)N[C@@H](C)CNC1=NC=CC(C2=CN(C(C)C)N=C2C3=CC(Cl)=CC(NS(=O)(C)=O)=C3F)=N1


Technical Data

Appearance:
Solid powder

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

Certificate of Analysis:

Safety Data Sheet (MSDS):

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, not in water

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


Additional Information

  
 The Raf mutation BRAF V600E is frequently upregulated in a variety of human tumors and results in the constitutive activation of the RAF/MEK/ERK signaling pathway that regulates cellular proliferation and survival.
 
 


References

1: Niessner H, Sinnberg T, Kosnopfel C, Smalley KSM, Beck D, Praetorius C, Mai M, Beissert S, Kulms D, Schaller M, Garbe C, Flaherty KT, Westphal D, Wanke I, Meier F. BRAF inhibitors amplify the pro-apoptotic activity of MEK inhibitors by inducing ER stress in NRAS-mutant melanoma. Clin Cancer Res. 2017 Jul 19. pii: clincanres.0098.2017. doi: 10.1158/1078-0432.CCR-17-0098. [Epub ahead of print] PubMed PMID: 28724666.

2: Maanaoui M, Saint-Jacques C, Gnemmi V, Frimat M, Lionet A, Hazzan M, Noël C, Provot F. Glomerulonephritis and granulomatous vasculitis in kidney as a complication of the use of BRAF and MEK inhibitors in the treatment of metastatic melanoma: A case report. Medicine (Baltimore). 2017 Jun;96(25):e7196. doi: 10.1097/MD.0000000000007196. PubMed PMID: 28640105; PubMed Central PMCID: PMC5484213.

3: Delord JP, Robert C, Nyakas M, McArthur GA, Kudchakar R, Mahipal A, Yamada Y, Sullivan RJ, Arance A, Kefford RF, Carlino MS, Hidalgo M, Gomez-Roca C, Michel D, Seroutou A, Aslanis V, Caponigro G, Stuart D, Moutouh-de Parseval L, Demuth T, Dummer R. Phase I Dose-Escalation and -Expansion Study of the BRAF Inhibitor Encorafenib (LGX818) in Metastatic BRAF-Mutant Melanoma. Clin Cancer Res. 2017 Jun 13. pii: clincanres.2923.2016. doi: 10.1158/1078-0432.CCR-16-2923. [Epub ahead of print] PubMed PMID: 28611198.

4: Grimaldi AM, Simeone E, Festino L, Vanella V, Strudel M, Ascierto PA. MEK Inhibitors in the Treatment of Metastatic Melanoma and Solid Tumors. Am J Clin Dermatol. 2017 May 23. doi: 10.1007/s40257-017-0292-y. [Epub ahead of print] Review. PubMed PMID: 28537004.

5: van Geel RMJM, Tabernero J, Elez E, Bendell JC, Spreafico A, Schuler M, Yoshino T, Delord JP, Yamada Y, Lolkema MP, Faris JE, Eskens FALM, Sharma S, Yaeger R, Lenz HJ, Wainberg ZA, Avsar E, Chatterjee A, Jaeger S, Tan E, Maharry K, Demuth T, Schellens JHM. A Phase Ib Dose-Escalation Study of Encorafenib and Cetuximab with or without Alpelisib in Metastatic BRAF-Mutant Colorectal Cancer. Cancer Discov. 2017 Jun;7(6):610-619. doi: 10.1158/2159-8290.CD-16-0795. Epub 2017 Mar 31. PubMed PMID: 28363909; PubMed Central PMCID: PMC5546207.

6: Turner MC, Rossfeld K, Salama AK, Tyler D, Beasley G. Can binimetinib, encorafenib and masitinib be more efficacious than currently available mutation-based targeted therapies for melanoma treatment? Expert Opin Pharmacother. 2017 Apr;18(5):487-495. doi: 10.1080/14656566.2017.1299710. Epub 2017 Mar 22. Review. PubMed PMID: 28277830.

7: Pascual LL, Muruzàbal RS, Gigli ML, Bayona JI. Cutaneous toxicity of a new BRAF inhibitor, LGX818 (encorafenib). Indian J Dermatol Venereol Leprol. 2017 Jan-Feb;83(1):102-104. doi: 10.4103/0378-6323.191130. PubMed PMID: 27679406.

8: Sparidans RW, Rosing H, Rood JJ, Schellens JH, Beijnen JH. Liquid chromatography-tandem mass spectrometric assay for therapeutic drug monitoring of the B-Raf inhibitor encorafenib, the EGFR inhibitors afatinib, erlotinib and gefitinib and the O-desmethyl metabolites of erlotinib and gefitinib in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Oct 15;1033-1034:390-8. doi: 10.1016/j.jchromb.2016.09.012. Epub 2016 Sep 11. PubMed PMID: 27639128.

9: Asati V, Bharti SK, Mahapatra DK. Mutant B-Raf Kinase Inhibitors as Anticancer Agents. Anticancer Agents Med Chem. 2016;16(12):1558-1575. Review. PubMed PMID: 27264268.

10: Masuishi T, Muro K. [Current Progress and Feasibility of Using Molecular-Targeted Agent Combinations for Metastatic Colorectal Cancer]. Gan To Kagaku Ryoho. 2016 Apr;43(4):408-12. Japanese. PubMed PMID: 27220786.

11: Henning B, Stieger P, Kamarachev J, Dummer R, Goldinger SM. Pyogenic granuloma in patients treated with selective BRAF inhibitors: another manifestation of paradoxical pathway activation. Melanoma Res. 2016 Jun;26(3):304-7. doi: 10.1097/CMR.0000000000000248. PubMed PMID: 27116335.

12: Adelmann CH, Ching G, Du L, Saporito RC, Bansal V, Pence LJ, Liang R, Lee W, Tsai KY. Comparative profiles of BRAF inhibitors: the paradox index as a predictor of clinical toxicity. Oncotarget. 2016 May 24;7(21):30453-60. doi: 10.18632/oncotarget.8351. PubMed PMID: 27028853; PubMed Central PMCID: PMC5058692.

13: Krepler C, Xiao M, Sproesser K, Brafford PA, Shannan B, Beqiri M, Liu Q, Xu W, Garman B, Nathanson KL, Xu X, Karakousis GC, Mills GB, Lu Y, Ahmed TA, Poulikakos PI, Caponigro G, Boehm M, Peters M, Schuchter LM, Weeraratna AT, Herlyn M. Personalized Preclinical Trials in BRAF Inhibitor-Resistant Patient-Derived Xenograft Models Identify Second-Line Combination Therapies. Clin Cancer Res. 2016 Apr 1;22(7):1592-602. doi: 10.1158/1078-0432.CCR-15-1762. Epub 2015 Dec 16. PubMed PMID: 26673799; PubMed Central PMCID: PMC4818716.

14: Li Z, Jiang K, Zhu X, Lin G, Song F, Zhao Y, Piao Y, Liu J, Cheng W, Bi X, Gong P, Song Z, Meng S. Encorafenib (LGX818), a potent BRAF inhibitor, induces senescence accompanied by autophagy in BRAFV600E melanoma cells. Cancer Lett. 2016 Jan 28;370(2):332-44. doi: 10.1016/j.canlet.2015.11.015. Epub 2015 Nov 14. PubMed PMID: 26586345.

15: Ascierto PA, Marincola FM, Atkins MB. What's new in melanoma? Combination! J Transl Med. 2015 Jul 4;13:213. doi: 10.1186/s12967-015-0582-1. PubMed PMID: 26141621; PubMed Central PMCID: PMC4491255.

16: Sullivan R, LoRusso P, Boerner S, Dummer R. Achievements and challenges of molecular targeted therapy in melanoma. Am Soc Clin Oncol Educ Book. 2015:177-86. doi: 10.14694/EdBook_AM.2015.35.177. Review. PubMed PMID: 25993155.

17: Scartozzi M, Giampieri R, Aprile G, Iacono D, Santini D, dell'Aquila E, Silvestris N, Gnoni A, Bonotto M, Puzzoni M, Demurtas L, Cascinu S. The distinctive molecular, pathological and clinical characteristics of BRAF-mutant colorectal tumors. Expert Rev Mol Diagn. 2015;15(8):979-87. doi: 10.1586/14737159.2015.1047346. Epub 2015 May 15. Review. PubMed PMID: 25975986.

18: Trinh VA, You Y, Hwu WJ. Treatment of BRAF-mutated advanced cutaneous melanoma. Chin Clin Oncol. 2014 Sep;3(3):28. doi: 10.3978/j.issn.2304-3865.2014.05.10. PubMed PMID: 25841454.

19: Galliker NA, Murer C, Kamarashev J, Dummer R, Goldinger SM. Clinical observation of panniculitis in two patients with BRAF-mutated metastatic melanoma treated with a combination of a BRAF inhibitor and a MEK inhibitor. Eur J Dermatol. 2015 Apr;25(2):177-80. doi: 10.1684/ejd.2014.2512. PubMed PMID: 25788221.

20: Drug combo beneficial in colorectal cancer. Cancer Discov. 2015 Feb;5(2):102. doi: 10.1158/2159-8290.CD-NB2014-186. Epub 2014 Dec 19. PubMed PMID: 25656881.