LC 2

Name: LC 2
Brand: Tocris Bioscience
SKU: 7420

Tocris Bioscience, part of Bio-Techne | Catalog # 7420

Citations (1)

COA / SDS

Selective KRAS Degrader (PROTAC®)

Key Product Details

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)
Molecular Weight:	1132.8

View Full Technical Details for LC 2

Technical Data
Citations

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 KRAS^G12Cin 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 KRAS^G12C 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

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
E3 ligase	VHL
DC₅₀ / D_max	250 nM (90%) - Degradation of KRAS^G12C in NCI-H23 cells after 24 h treatment
Selectivity confirmed by global proteomics	No

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 for LC 2

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
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.

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.

De Vita The missing link between (un)druggable and degradable KRAS. ACS Cent.Sci. 2020 PMID: 32875070
Bond Targeted degradation of oncogenic KRAS ^G12C by VHL-recruiting PROTACs. ACS Cent.Sci. 2020 PMID: 32875077