LC 2

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Description: Selective KRAS Degrader (PROTAC®)
Chemical Name: (2S,4R)-1-((S)-2-(3-(3-((S)-2-(((7-(8-Chloronaphthalen-1-yl)-4-((S)-3-(cyanomethyl)-4-(2-fluoroacryloyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)oxy)methyl)pyrrolidin-1-yl)propoxy)propanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide
Purity: ≥95% (HPLC)
Literature (4)

Biological Activity for LC 2

LC 2 is a mutant-selective KRAS Degrader (PROTAC®), comprising a ligand for the von Hippel Lindau E3 ligase joined to the KRAS inhibitor MRTX849. LC 2 induces selective degradation of KRASG12C in cancer cell lines without inducing degradation of any other mutants (DC50 = 0.25-0.76 μM), leading to suppression of MAPK signaling and modulation of ERK signaling in both homozygous and heterozygous KRASG12C cancer cell lines. LC 2 inhibits phosphorylation of ERK in SW1573 cell lines.

Negative control LC 2 Epimer (Cat. No. 7421) also available.

PROTAC® is a registered trademark of Arvinas Operations, Inc., and is used under license.

Technical Data for LC 2

E3 ligase VHL
DC50 / Dmax 250 nM (90%) - Degradation of KRASG12C in NCI-H23 cells after 24 h treatment
Selectivity confirmed by global proteomics No
M. Wt 1132.8
Formula C59H71ClFN11O7S
Storage Store at -20°C
Purity ≥95% (HPLC)
CAS Number 2502156-03-6
PubChem ID 154727765
Smiles CC1=C(C2=CC=C(C=C2)CNC([C@@H]3C[C@H](CN3C([C@H](C(C)(C)C)NC(CCOCCCN4CCC[C@H]4COC5=NC(N6CCN(C(C(F)=C)=O)[C@H](C6)CC#N)=C7CCN(C8=CC=CC9=C8C(Cl)=CC=C9)CC7=N5)=O)=O)O)=O)SC=N1

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.

Tocris products are intended for laboratory research use only, unless stated otherwise.

Solubility Data for LC 2

Solvent Max Conc. mg/mL Max Conc. mM
DMSO 113.28 100

Preparing Stock Solutions for LC 2

The following data is based on the product molecular weight 1132.8. 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.

Select a batch to recalculate based on the batch molecular weight:
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 0.88 mL 4.41 mL 8.83 mL
5 mM 0.18 mL 0.88 mL 1.77 mL
10 mM 0.09 mL 0.44 mL 0.88 mL
50 mM 0.02 mL 0.09 mL 0.18 mL

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References for LC 2

References are publications that support the biological activity of the product.

Bond et al (2020) Targeted degradation of oncogenic KRAS G12C by VHL-recruiting PROTACs. ACS Cent.Sci. 6 1367 PMID: 32875077

De Vita et al (2020) The missing link between (un)druggable and degradable KRAS. ACS Cent.Sci. 6 1281 PMID: 32875070

If you know of a relevant reference for LC 2, please let us know.

Keywords: LC 2, LC 2 supplier, LC2, PROTACs, targeted, protein, degraders, degradation, von, Hippel, Lindau, E3, ligase, KRAS, ERK, selective, VHL, MRTX849, Protein, Degraders, Ras, GTPases, 7420, Tocris Bioscience

Citations for LC 2

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Literature in this Area

Tocris offers the following scientific literature in this area to showcase our products. We invite you to request* your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.

Targeted Protein Degradation Research Product Guide

Targeted Protein Degradation Research Product Guide

This brochure highlights the tools and services available from Bio-Techne to support Targeted Protein Degradation research, including:

  • Active Degraders
  • TAG Degradation Platform
  • Degrader Building Blocks
  • Ubiquitin-Proteasome System Proteins
  • Assays for Protein Degradation
Epigenetics Scientific Review

Epigenetics Scientific Review

Written by Susanne Müller-Knapp and Peter J. Brown, this review gives an overview of the development of chemical probes for epigenetic targets, as well as the impact of these tool compounds being made available to the scientific community. In addition, their biological effects are also discussed. Epigenetic compounds available from Tocris are listed.

Epigenetics in Cancer Poster

Epigenetics in Cancer Poster

This poster summarizes the main epigenetic targets in cancer. The dysregulation of epigenetic modifications has been shown to result in oncogenesis and cancer progression. Unlike genetic mutations, epigenetic alterations are considered to be reversible and thus make promising therapeutic targets.

Targeted Protein Degradation Poster

Targeted Protein Degradation Poster

Degraders (e.g. PROTACs) are bifunctional small molecules, that harness the Ubiquitin Proteasome System (UPS) to selectively degrade target proteins within cells. They consist of three covalently linked components: an E3 ubiquitin ligase ligand, a linker and a ligand for the target protein of interest. Authored in-house, this poster outlines the generation of a toolbox of building blocks for the development of Degraders. The characteristics and selection of each of these components are discussed. Presented at EFMC 2018, Ljubljana, Slovenia