457
Views
7
CrossRef citations to date
0
Altmetric
Review

A patent review of BRAF inhibitors: 2013-2018

, &
Pages 595-603 | Received 23 Mar 2019, Accepted 03 Jul 2019, Published online: 13 Jul 2019

References

  • Lahiry P, Torkamani A, Schork NJ, et al. Kinase mutations in human disease: interpreting genotype–phenotype relationships. Nat Rev Genet. 2010;11:60–74.
  • Wang PF, Wang ZF, Qiu HY, et al. Identification and biological evaluation of novel type II B‐RafV600E inhibitors. ChemMedChem. 2018;13:2558–2566.
  • Welsh SJ, Rizos H, Scolyer RA, et al. Resistance to combination BRAF and MEK inhibition in metastatic melanoma: where to next? Eur J Cancer. 2016;62:76–85.
  • Kim EK, Choi E-J. Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta Mol Basis Dis. 2010;4:396–405.
  • Sommerer F, Vieth M, Markwarth A, et al. Mutations of BRAF and KRAS2 in the development of barrett’s adenocarcinoma. Oncogene. 2004;2:554.
  • Nguyen-Ngoc T, Bouchaab H, Adjei AA, et al. BRAF alterations as therapeutic targets in non–small-cell lung cancer. J Thorac Oncol. 2015;10:1396–1403.
  • Roskoski R. Jr . Allosteric MEK1/2 inhibitors including cobimetanib and trametinib in the treatment of cutaneous melanomas. Pharmacol Res. 2017;117:20–31.
  • Shirley M. Encorafenib and binimetinib: first global approvals. Drugs. 2018;12:1277–1284.
  • Sosman JA, Kim KB, Schuchter L, et al. Survival in BRAF V600–mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012;8:707–714.
  • Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;26:2507–2516.
  • Robert C, Karaszewska B, Schachter J, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;1:30–39.
  • Long GV, Stroyakovskiy D, Gogas H, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015;386:444–451.
  • Wang PF, Zhang YJ, Wang D, et al. Design, synthesis, and biological evaluation of new B-RafV600E kinase inhibitors. Bioorg Med Chem. 2018;9:2372–2380.
  • Rizos H, Menzies AM, Pupo GM, et al. BRAF inhibitor resistance mechanisms in metastatic melanoma: spectrum and clinical impact. Clin Cancer Res. 2014;7:1965–1977.
  • Menzies AM, Kefford RF, Long GV. Paradoxical oncogenesis: are all BRAF inhibitors equal? Pigment Cell Melanoma Res. 2013;5:611–615.
  • Koelblinger P, Thuerigen O, Dummer R. Development of encorafenib for BRAF-mutated advanced melanoma. Curr Opin Oncol. 2018;2:125–133.
  • Dummer R, Ascierto PA, Gogas HJ, et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2018;5:603–615.
  • Dummer R, Ascierto PA, Gogas H, et al. Overall survival in COLUMBUS: A phase 3 trial of encorafenib (ENCO) plus binimetinib (BINI) vs vemurafenib (VEM) or enco in BRAF-mutant melanoma. J Clin Oncol. 2018;36:9504.
  • Fernández-Sartorio C, Boada A, Chavez-Bourgeois MM, et al. Aged-looking skin and encorafenib: an adverse event of BRAF inhibitors. Melanoma Res. 2018;2:160–162.
  • Kuske M, Westphal D, Wehner R, et al. Immunomodulatory effects of BRAF and MEK inhibitors: implications for melanoma therapy. Pharmacol Res. 2018;136:151–159.
  • Asati V, Mahapatra DK, Bharti SK. PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways inhibitors as anticancer agents: structural and pharmacological perspectives. Eur J Med Chem. 2016;109:314–341.
  • Roskoski R. Jr . Targeting oncogenic Raf protein-serine/threonine kinases in human cancers. Pharmacol Res. 2018;135:239–258.
  • Karoulia Z, Gavathiotis E, Poulikakos PI. New perspectives for targeting RAF kinase in human cancer. Nat Rev Cancer. 2017;11:676–691.
  • Van Linden OP, Kooistra AJ, Leurs R, et al. KLIFS: a knowledge-based structural database to navigate kinase–ligand interaction space. J Med Chem. 2013;2:249–277.
  • Tentori L, Lacal PM, Graziani G. Challenging resistance mechanisms to therapies for metastatic melanoma. Trends Pharmacol Sci. 2013;12:656–666.
  • Jang S, Atkins M. Treatment of BRAF‐mutant melanoma: the role of vemurafenib and other therapies. Clin Pharmacol Ther. 2014;1:24–31.
  • Wang ZF, Wang PF, Ma JT, et al. Design of potent B‐RafV600E inhibitors by multiple copy simulation search strategy. Chem Biol Drug Des. 2018;2:567–574.
  • Kooistra AJ, Kanev GK, van Linden OP, et al. KLIFS: a structural kinase-ligand interaction database. Nucleic Acids Res. 2015;44:365–371.
  • Wang PF, Qiu HY, Wang ZF, et al. Identification of novel B-RafV600E inhibitors employing FBDD strategy. Biochem Pharmacol. 2017;132:63–76.
  • Ung PM-U, Rahman R, Schlessinger A. Redefining the protein kinase conformational space with machine learning. Cell Chem Biol. 2018;25:916–924.
  • Verkhivker G. Molecular dynamics simulations and modelling of the residue interaction networks in the BRAF kinase complexes with small molecule inhibitors: probing the allosteric effects of ligand-induced kinase dimerization and paradoxical activation. Mol Biosyst. 2016;10:3146–3165.
  • Pan JH, Zhou H, Zhu SB, et al. Development of small-molecule therapeutics and strategies for targeting RAF kinase in BRAF-mutant colorectal cancer. Cancer Manag Res. 2018;10:2289.
  • Ibrahim PN, Zhang C, Spevak W, et al. Compounds and methods for kinase modulation, and indications thereof. US2014128373. 2014.
  • Ibrahim PN, Zhang C, Spevak W, et al. PLX-8394 or PLX-7904 for use in the treatment of BRAF-V600-related diseases. WO2016191296. 2016.
  • Zhang C, Spevak W, Zhang Y, et al. RAF inhibitors that evade paradoxical MAPK pathway activation. Nature. 2015;526:583–586.
  • Le K, Blomain ES, Rodeck U, et al. Selective RAF inhibitor impairs ERK 1/2 phosphorylation and growth in mutant NRAS, vemurafenib‐resistant melanoma cells. Pigment Cell Melanoma Res. 2013;4:509–517.
  • Henry JR, Kaufman MD, Peng SB, et al. Discovery of 1-(3,3-Dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)urea (LY3009120) as a Pan-RAF inhibitor with minimal paradoxical activation and activity against BRAF or RAS mutant tumor cells. J Med Chem. 2015;10:4165–4179.
  • Lilly Co Eli. 2-Amino, 6-phenyl substituted pyrido [2,3-d] pyrimidine derivatives useful as RAF kinase inhibitors. WO2013134243. 2013.
  • Sloot S, Fedorenko IV, Smalley KS, et al. Long-term effects of BRAF inhibitors in melanoma treatment: friend or foe? Expert Opin Pharmacother. 2014;15:589–592.
  • Novartis AG. Biaryl amide compounds as kinase inhibitors. WO2014151616. 2014.
  • Lilly Co Eli. Raf inhibitor compounds. US2015105367, 2015.
  • Anforth R, Fernandez-Peñas P, Long GV. Cutaneous toxicities of RAF inhibitors. Lancet Oncol. 2013;1:11–18.
  • Tambe M, Karjalainen E, Vaha-Koskela M, et al. Paradox-breaker pan-RAF inhibitors induce an AML-specific cytotoxic response and synergize with venetoclax to display superior antileukemic activity. Blood. 2018;132:2210.
  • Sun J, Zager JS, Eroglu Z. Encorafenib/binimetinib for the treatment of BRAF-mutant advanced, unresectable, or metastatic melanoma: design, development, and potential place in therapy. Onco Targets Ther. 2018;11:9081–9089.
  • Roskoski R. Jr. RAF protein-serine/threonine kinases: structure and regulation. Biochem Biophys Res Commun. 2010;3:313–317.
  • Roskoski R. Jr. MEK1/2 dual-specificity protein kinases: structure and regulation. Biochem Biophys Res Commun. 2012;1:5–10.
  • Hu-Lieskovan S, Robert L, Moreno BH, et al. Combining targeted therapy with immunotherapy in BRAF-mutant melanoma: promise and challenges. J Clin Oncol. 2014;21:2248–2254.
  • Marx J. Obstacle for promising cancer therapy. Science. 2002;295:1444.
  • Amaral T, Sinnberg T, Meier F, et al. The mitogen-activated protein kinase pathway in melanoma part I–activation and primary resistance mechanisms to BRAF inhibition. Eur J Cancer. 2017;73:85–92.
  • Lito P. Methods and compositions for treatment of BRAF mutant cancers. WO2018107146. 2018.
  • Genentech Inc. Combination treatments comprising c-met antagonists and b-raf antagonists. WO2013043715. 2013.
  • Hoos A. Combinations of an anti-pd-l1 antibody and a MEK inhibitor and/or a BRAF inhibitor. WO2014195852. 2014.
  • Legos JJ, Cornfeld MJ. Method of treating cancer using combination of BRAF inhibitor, MEK inhibitor, and anti-CTLA-4 antibody. WO2013019620. 2013.
  • Onconthyreon Inc. Combination therapy using pi3 kinase and BRAF inhibitors. WO2014031856. 2014.
  • Glaxosmithkline Llc. Combination. US2014350039. 2014.
  • Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor US2015080372. 2015.
  • Caponigro G, Horn-Spirohn T, Lehar J. Pharmaceutical combination comprising the PI3K inhibitor alpelisib and the B-RAF inhibitor dabrafenib; the use of such combination in the treatment or prevention of cancer. US2018243279. 2018.
  • Novartis AG. Pharmaceutical combinations comprising a B-RAF inhibitor, an EGFR inhibitor and optionally a PI3K-alpha inhibitor WO2014025688. 2014.
  • Novartis AG. Combination of BRAF and VEGF inhibitors US2016243118. 2016.
  • Novartis AG. Combination therapy. WO2014147573. 2014.
  • Jure-Kunkel M, Wigginton JM, Gupta AK. Combination of anti-ctla4 antibody with BRAF inhibitors for the synergistic treatment of proliferative diseases. US20130156768. 2013.
  • Glaxosmithkline Llc. Method of treating cancer with MEGEA3 immunotherapeutic with BRAF inhibitor and/or MEK inhibitor. US2015147350. 2015.
  • Genentech Inc. Methods of treating cancer using B-RAF inhibitors and immune checkpoint inhibitor. WO2017087851. 2017.
  • Univ Columbia. Combination of BRAF inhibitor, talimogene laherparepvec, and immune checkpoint inhibitor for use in the treatment cancer (melanoma). WO2018075447. 2018.
  • He YJ, Howard LM, Chen X, et al. Compound preparation for treating BRAF inhibitor-resistant melanoma. CN107569485. 2017.
  • Synta Pharmaceuticals Corp. Combination therapy of HSP90 inhibitors with BRAF inhibitors. US2014256680. 2014.
  • Novartis AG. Pharmaceutical combinations of a CDK4/6 inhibitor and a B-RAF inhibitor. WO2014018725. 2014.
  • Novartis AG. Pharmaceutical combination comprising a B-RAF inhibitor and a histone deacetylase inhibitor and their use in the treatment of proliferative diseases. WO2014072493. 2014.
  • Novartis AG. Combination of MDM2 inhibitor and BRAF inhibitor and their use. WO2015084804. 2015.
  • Wang J, Chen JJ, Miller DD, et al. Compounds for treatment of cancer. US20180325872. 2018.
  • Yao Z, Gao Y, Su W, et al. RAF inhibitor PLX8394 selectively disrupts BRAF dimers and RAS-independent BRAF-mutant-driven signaling. Nat Med. 2019;2:284–291.
  • Takeda Pharmaceutical. Administration of a RAF inhibitor and a MEK inhibitor in the treatment of melanoma. US2015126533. 2015.
  • Zhang RH. Benzimidazole compound, and preparation method, intermediate and application thereof. CN105949178. 2015.
  • Zhou Y, Xu T, Wang ZC, et al. Anti-tumor drug having multiple kinase inhibition and preparation method and application thereof. CN108440404. 2018.
  • Neupharma Inc. Certain chemical entities, compositions, and methods. WO2013112950. 2013.
  • Springer CJ, Niculescu-Duvaz D, Niculescu-Duvaz I, et al. Pyrido[2,3-b]pyrazin-8-substituted compounds and their use. US2016002230. 2016.
  • Zhou CY, Zhang Gl. Fused tricyclic amide compounds as multiple kinase inhibitors. US2016159820. 2016.
  • Zhang Q, Zhang HB, Yang LF. Urea-substituted aromatic ring-linked dioxane-quinazoline and -linked dioxane-quinoline compounds, preparation method therefor and use thereof. WO2018157730. 2018.
  • Wu XY, Wang YY, Fu Y, et al. 1H-pyrazolo[3,4-d]pyrimidin compound and preparation method and application thereof. CN107383014. 2017.
  • Zhou Y. Substitutional imidazole kinase inhibitor. CN103159735. 2013.
  • Zhou Y. Substitutional pyrazol kinase inhibitor. CN103159736. 2013.
  • An XX, Bie PY, Yang WL, et al. Diaryl-substituted pyrazolo ring derivative and preparation method thereof, and applications of diaryl-substituted pyrazolo ring derivative in medicine field. CN104829613. 2014.
  • Wu YQ. Benzene sulfonamide pyrazole kinase inhibitor. CN103965170. 2013.
  • Wu YQ. Benzenesulfonamideoxazole and thiazole kinase inhibitor. CN103965180. 2013.
  • Folmer BJB, Man DAPA, Gernette ES, et al. Thieno (2,3b) pyrazine compounds as B-RAF inhibitors. US2013079341. 2013.
  • Pan SF, Tellew JE, Wan YQ, et al. Compounds and compositions as protein kinase inhibitors. US2013143899. 2013.
  • Boehringer Ingelheim Int. B-RAF kinase inhibitors. US2013190286. 2013.
  • Siddiqui MA, Zhao LY, Mandal AK. Heterocyclic compounds as B-RAF inhibitors for treatment of cancer. US2014323519. 2014.
  • Array Biopharma Inc. Compounds and compositions as protein kinase inhibitors. US2018297986. 2018.
  • Neupharma Inc. Certain chemical entities, compositions, and methods. US2014343068. 2014.
  • Neupharma Inc. Certain chemical entities, compositions, and methods. US2016009663. 2016.
  • Neupharma Inc. Certain chemical entities, compositions, and methods. US2018134669. 2018.
  • Ambit Biosciences Corp. Raf kinase modulator compounds and methods of use thereof. US2017298029. 2017.
  • Ambit Biosciences Corp. 1-(3-(6,7-Dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea as RAF kinase modulator in the treatment of cancer diseases. EP2947072. 2015.
  • Redxpharma Ltd. Compounds. GB2517988. 2015.
  • Martin-Liberal J. Encorafenib plus binimetinib: an embarrassment of riches. Lancet Oncol. 2018;10:1263–1264.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.