LC 2

Pricing Availability   Qty
Description: Selective KRAS 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)
Datasheet
Citations
Reviews
Literature (4)

Biological Activity for LC 2

LC 2 is a mutant-selective PROTAC® Degrader of KRAS, 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
InChI Key ZCGQZLKPUVGCBQ-HLMPTVQRSA-N
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
Solubility
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

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

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, Active, Degraders, Ras, GTPases, 7420, Tocris Bioscience

Citations for LC 2

Citations are publications that use Tocris products.

Currently there are no citations for LC 2. Do you know of a great paper that uses LC 2 from Tocris? Please let us know.

Reviews for LC 2

There are currently no reviews for this product. Be the first to review LC 2 and earn rewards!

Have you used LC 2?

Submit a review and receive an Amazon gift card.

$50/€35/£30/$50CAN/¥300 Yuan/¥5000 Yen for first to review with an image

$25/€18/£15/$25CAN/¥75 Yuan/¥1250 Yen for a review with an image

$10/€7/£6/$10 CAD/¥70 Yuan/¥1110 Yen for a review without an image

Submit a Review

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