FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2887832968> ?p ?o ?g. }

• W2887832968 abstract "The mitogen-activated protein kinase (MAPK) signaling pathway is frequently activated in human cancers due to genetic alterations that can occur at multiple nodes, the most prevalent of which are mutations in RAS or BRAF. While BRAFV600 mutant tumors are responsive to RAF inhibitors such as dabrafenib and vemurafenib, these drugs are ineffective in RAS mutant cancers and tumors expressing other RAF mutations. CRAF kinase functions as a critical effector in mutant RAS and Class II/III BRAF mutant tumors and plays a role in feedback-mediated pathway reactivation following MEK inhibition. Thus, selective inhibitors that potently inhibit the activity of CRAF could be both effective in blocking mutant RAS and BRAF signaling and in inhibiting feedback-mediated activation in combination with a MEK inhibitor. LXH254 is a type II ATP-competitive inhibitor that inhibits both B- and CRAF kinase activities at picomolar concentrations with a high degree of selectivity against a panel of 456 human kinases and in cell-based assays. LXH254 not only inhibits MAPK signaling activity in tumor models harboring BRAFV600 mutation, but also inhibits mutant N- and KRAS-driven signaling due to its ability to inhibit both RAF monomers and dimers with similar potencies. LXH254 is orally bioavailable, demonstrates a direct PK/PD relationship and causes tumor regression in multiple cell line and primary human tumor derived xenograft models at well-tolerated doses. LXH254 represents a next generation RAF inhibitor that is differentiated from other RAF inhibitors in this class due to the high degree of selectivity. In preclinical efficacy and toxicology studies, LXH254 demonstrated a relatively wide therapeutic index which should enable effective interrogation of RAF inhibition in patients with decreased risk for off-target toxicity. LXH254 is currently in a Phase I trial in patients with solid tumors expressing MAPK pathway mutations. Citation Format: Darrin D. Stuart, Wenlin Shao, Yuji Mishina, Yun Feng, Giordano Caponigro, Vesselina G. Cooke, Stacey Rivera, Fang Shen, Joshua Korn, Lesley A. Mathews Griner, Giselle Nishiguchi, Benjamin Taft, Lifeng Wan, Sharadha Subramanian, Yan Lou, Lina Setti, Matthew Burger, Victor Tamez, Alice Rico, Robert Aversa, John Tellew, Jacob R. Haling, Valery Polyakov, Amy Lambert, Richard Zang, Ann Van Abbema, Mohamad Hekmat-Nejad, Payman Amiri, Mallika Singh, Nicholas Keen, Michael P. Dillon, Emma Lees, William R. Sellers, Savithri Ramurthy. Pharmacological profile and anti-tumor properties of LXH254, a highly selective RAF kinase inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr DDT01-04." @default.
• W2887832968 created "2018-08-22" @default.
• W2887832968 creator A5000020580 @default.
• W2887832968 creator A5001097709 @default.
• W2887832968 creator A5001240412 @default.
• W2887832968 creator A5002731606 @default.
• W2887832968 creator A5002936473 @default.
• W2887832968 creator A5003410549 @default.
• W2887832968 creator A5004053040 @default.
• W2887832968 creator A5005120818 @default.
• W2887832968 creator A5019285942 @default.
• W2887832968 creator A5021784750 @default.
• W2887832968 creator A5025118565 @default.
• W2887832968 creator A5029870688 @default.
• W2887832968 creator A5032586778 @default.
• W2887832968 creator A5036314552 @default.
• W2887832968 creator A5036903965 @default.
• W2887832968 creator A5046475464 @default.
• W2887832968 creator A5049772515 @default.
• W2887832968 creator A5052809480 @default.
• W2887832968 creator A5053227790 @default.
• W2887832968 creator A5057024955 @default.
• W2887832968 creator A5057346782 @default.
• W2887832968 creator A5057362852 @default.
• W2887832968 creator A5059882947 @default.
• W2887832968 creator A5060683698 @default.
• W2887832968 creator A5062280823 @default.
• W2887832968 creator A5064934325 @default.
• W2887832968 creator A5070645392 @default.
• W2887832968 creator A5070651116 @default.
• W2887832968 creator A5073974293 @default.
• W2887832968 creator A5074912070 @default.
• W2887832968 creator A5075733194 @default.
• W2887832968 creator A5078185401 @default.
• W2887832968 creator A5080831528 @default.
• W2887832968 creator A5084470001 @default.
• W2887832968 date "2018-07-01" @default.
• W2887832968 modified "2023-10-14" @default.
• W2887832968 title "Abstract DDT01-04: Pharmacological profile and anti-tumor properties of LXH254, a highly selective RAF kinase inhibitor" @default.
• W2887832968 doi "https://doi.org/10.1158/1538-7445.am2018-ddt01-04" @default.
• W2887832968 hasPublicationYear "2018" @default.
• W2887832968 type Work @default.
• W2887832968 sameAs 2887832968 @default.
• W2887832968 citedByCount "1" @default.
• W2887832968 countsByYear W28878329682020 @default.
• W2887832968 crossrefType "proceedings-article" @default.
• W2887832968 hasAuthorship W2887832968A5000020580 @default.
• W2887832968 hasAuthorship W2887832968A5001097709 @default.
• W2887832968 hasAuthorship W2887832968A5001240412 @default.
• W2887832968 hasAuthorship W2887832968A5002731606 @default.
• W2887832968 hasAuthorship W2887832968A5002936473 @default.
• W2887832968 hasAuthorship W2887832968A5003410549 @default.
• W2887832968 hasAuthorship W2887832968A5004053040 @default.
• W2887832968 hasAuthorship W2887832968A5005120818 @default.
• W2887832968 hasAuthorship W2887832968A5019285942 @default.
• W2887832968 hasAuthorship W2887832968A5021784750 @default.
• W2887832968 hasAuthorship W2887832968A5025118565 @default.
• W2887832968 hasAuthorship W2887832968A5029870688 @default.
• W2887832968 hasAuthorship W2887832968A5032586778 @default.
• W2887832968 hasAuthorship W2887832968A5036314552 @default.
• W2887832968 hasAuthorship W2887832968A5036903965 @default.
• W2887832968 hasAuthorship W2887832968A5046475464 @default.
• W2887832968 hasAuthorship W2887832968A5049772515 @default.
• W2887832968 hasAuthorship W2887832968A5052809480 @default.
• W2887832968 hasAuthorship W2887832968A5053227790 @default.
• W2887832968 hasAuthorship W2887832968A5057024955 @default.
• W2887832968 hasAuthorship W2887832968A5057346782 @default.
• W2887832968 hasAuthorship W2887832968A5057362852 @default.
• W2887832968 hasAuthorship W2887832968A5059882947 @default.
• W2887832968 hasAuthorship W2887832968A5060683698 @default.
• W2887832968 hasAuthorship W2887832968A5062280823 @default.
• W2887832968 hasAuthorship W2887832968A5064934325 @default.
• W2887832968 hasAuthorship W2887832968A5070645392 @default.
• W2887832968 hasAuthorship W2887832968A5070651116 @default.
• W2887832968 hasAuthorship W2887832968A5073974293 @default.
• W2887832968 hasAuthorship W2887832968A5074912070 @default.
• W2887832968 hasAuthorship W2887832968A5075733194 @default.
• W2887832968 hasAuthorship W2887832968A5078185401 @default.
• W2887832968 hasAuthorship W2887832968A5080831528 @default.
• W2887832968 hasAuthorship W2887832968A5084470001 @default.
• W2887832968 hasConcept C104317684 @default.
• W2887832968 hasConcept C143065580 @default.
• W2887832968 hasConcept C184235292 @default.
• W2887832968 hasConcept C185592680 @default.
• W2887832968 hasConcept C2776131300 @default.
• W2887832968 hasConcept C2777658100 @default.
• W2887832968 hasConcept C2778472372 @default.
• W2887832968 hasConcept C2781187634 @default.
• W2887832968 hasConcept C2994587330 @default.
• W2887832968 hasConcept C501734568 @default.
• W2887832968 hasConcept C502942594 @default.
• W2887832968 hasConcept C55493867 @default.
• W2887832968 hasConcept C57074206 @default.
• W2887832968 hasConcept C86803240 @default.
• W2887832968 hasConcept C95444343 @default.
• W2887832968 hasConcept C97029542 @default.
• W2887832968 hasConcept C98274493 @default.
• W2887832968 hasConceptScore W2887832968C104317684 @default.
• W2887832968 hasConceptScore W2887832968C143065580 @default.
• W2887832968 hasConceptScore W2887832968C184235292 @default.

• next