KRAS G12C Protein, Human, Recombinant, Biotinylated, GppNHp-Loaded

N-terminal AviTag™, N-terminal 8XHis

High-purity KRAS G12C protein supplied in a defined GppNHp-loaded active-state conformation for controlled biochemical workflows, including SPR, BLI, ELISA, pull-down, AlphaScreen, MST, effector binding assays, nucleotide-state-dependent inhibitor profiling, and oncology drug discovery applications.

Available Sizes

0.05 mg
$ 550.00
0.1 mg
$ 800.00
1.0 mg
$ 6,000.00

Ships with Certificate of Analysis (CoA)

Product Overview

KRAS G12C is the target of the first FDA-approved direct KRAS inhibitor (sotorasib, 2021) and adagrasib (2022). Both drugs covalently engage Cys12 in the GDP-bound (inactive) state. However, a growing body of evidence suggests that non-covalent G12C inhibitors and next-generation compounds may also target the active (GTP-bound) conformation. Understanding conformation-selective engagement requires access to both GDP-loaded and GppNHp-loaded G12C protein.

This product provides recombinant human KRAS G12C (isoform KRAS4B, aa 1–185) loaded with GppNHp (guanosine 5’-[β,γ-imido]triphosphate), a non-hydrolyzable GTP analogue that stabilizes the active switch conformation. Site-specific biotinylation at the N-terminal AviTag™ enables direct capture on streptavidin surfaces for SPR, BLI, and AlphaScreen assays without additional coupling steps.

Key Features

  • KRAS G12C clinically relevant mutation
  • Supplied pre-loaded with GppNHp
  • N-terminal AviTag™, N-terminal 8XHis tagged construct
  • Site-specifically biotinylated at the N-terminus
  • High purity recombinant protein
  • Optimized for binding assays
  • Research Use Only (RUO)

Applications

  • SPR
  • BLI
  • ELISA
  • Pull-down
  • AlphaScreen
  • MST
  • Effector binding assays
  • Nucleotide-state-dependent inhibitor profiling
  • Protein–protein interaction studies
  • Drug discovery workflows

Technical Notes

Active-state G12C and the switch II pocket

In the GDP-bound state, KRAS G12C exposes a cryptic pocket (S-IIP) adjacent to switch II that is targeted by sotorasib and adagrasib. This pocket is absent in the active (GTP/GppNHp-bound) state. Researchers using this GppNHp-loaded product should be aware that S-IIP targeting covalent inhibitors will not engage Cys12 in this conformation. Use this product for active-state binders and non-covalent inhibitor discovery.

Cys12 accessibility in GppNHp state

GppNHp loading repositions switch II and reduces Cys12 solvent exposure compared to the GDP state. The free thiol at Cys12 remains present but is less accessible. Mass spectrometry confirmation of modification stoichiometry is recommended if covalent labeling is attempted with this product.

Biological Context & Applications

Cancer Indications

Non-small cell lung cancer (NSCLC), colorectal cancer, pancreatic cancer, lung adenocarcinoma, bladder cancer (subset), head and neck cancer (subset)

Binding Partners

RAF1, BRAF, PI3K, RalGDS, SOS1

Application Notes

Standard for KRAS inhibitor screening and biochemical assays

Protein Specifications

Gene KRAS
Mutation G12C
Nucleotide State GppNHp-Loaded
Organism Human
Tag N-terminal AviTag™, N-terminal 8XHis
Expression System E. coli
Purity >90% by Coomassie staining
Endotoxin <1 EU/mg
Biotinylated Yes
Oncogenic Status Oncogenic
Assay Compatibility SPR, BLI, ELISA, Pull-down, AlphaScreen, MST, Effector binding assays, Nucleotide-state-dependent inhibitor profiling
UniProt ID P01116-2
Amino Acid Range 1-185
Buffer 20 mM HEPES, pH 7.5, 100 mM NaCl, 1 mM MgCl2, 1 mM 2-mercapthoethanol, 10% glycerol
Storage -80 °C

Quality Control

  • Purity validated by SDS-PAGE
  • Identity confirmed by mass spectrometry
  • Assay compatibility verified
  • A Certificate of Analysis (CoA) is provided with every shipment

Ordering Information

Size Catalog No. Price Quote
0.05 mg KRAS12C-GPPNHP-301-005 $ 550.00 Request Quote
0.1 mg KRAS12C-GPPNHP-301-01 $ 800.00 Request Quote
1.0 mg KRAS12C-GPPNHP-301-1 $ 6,000.00 Request Quote
Need larger quantities or custom formats? We offer bulk pricing and custom production.
Request Bulk Quote

Typical response time: 1 business day

Custom Services

Need a different format, mutation, or production scale? We offer custom RAS protein engineering tailored to your research.

Custom Mutations

Alternative KRAS variants, including rare and novel mutations.

Tag & Labeling Options

His-tag, AviTag™, biotinylation, fluorescent labeling, or tag-free formats.

Scale-Up Production

From research-scale to bulk manufacturing for screening and preclinical work.

Protein Complexes

Complex formation such as KRAS–RAF-RBD and other binding partners.

Nucleotide Loading

Pre-load KRAS proteins with defined nucleotides, including GppNHp (non-hydrolyzable GTP analog) or GDP, for consistent assay-ready performance.

Tell us your mutation, format, or assay requirements and we’ll provide a tailored quote.

Request Custom Quote Email Us

Fast turnaround • Dedicated scientific support • Confidential projects

Related Products

Other KRAS mutants and formats available.

Research Use Only. Not for diagnostic or therapeutic use.