KRAS Proteins for Drug Discovery | Amid Biosciences
The KRAS protein is the most common oncogenic driver in human cancers. Considered undruggable for decades, recent advances have made KRAS-targeted therapies one of the most promising areas of cancer treatment. With FDA-approved KRAS inhibitors [1–3] now in the clinic and additional compounds in the pipeline [4–6], the demand for high-quality KRAS research reagents has never been higher.
Amid Biosciences supports this critical research wave with a broad portfolio of wild-type, mutant, biotinylated, and unmodified recombinant KRAS proteins manufactured in Santa Clara, California, and shipped next-day to labs across the U.S.
Why KRAS Matters Right Now
KRAS (Kirsten Rat Sarcoma viral proto-oncogene) encodes a small GTPase that acts as a molecular switch in cell signaling. In its normal state, it cycles between an active GTP-bound form and an inactive GDP-bound form. When mutations lock KRAS in the "on" position, downstream cascades - including RAF–MEK–ERK and PI3K–AKT - drive uncontrolled cell proliferation. KRAS mutations mainly contain 21 missense mutations, with G12D, G12V, and G12C being the most common.
KRAS mutations are present in more than 90% of pancreatic cancers, 50% of colorectal cancers, and 35% of non-small cell lung cancers, making it the most commonly mutated oncogene in human cancer.
Because of its smooth surface, KRAS appeared to lack obvious drug-binding pockets. That changed with the 2013 discovery of a cryptic "switch-II pocket" in the G12C mutant by Dr. Kevan Shokat's lab at UCSF. This breakthrough ultimately produced sotorasib and adagrasib, the first FDA-approved KRAS-targeted drugs. Building on this initial success, the development landscape has expanded beyond the G12C mutation. Today, researchers are targeting variants like G12D, G12V, G12R, and Q61H and exploring novel modalities such as pan-KRAS inhibitors, SOS1 degraders, SHP2/KRAS combination strategies, and KRAS-targeted PROTACs.
Recent data highlights just how promising this next generation of therapeutics has become. Phase 3 trial data from Revolution Medicines demonstrated that daraxonrasib (RMC-6236), a RAS(ON) inhibitor targeting multiple mutations including G12D and G12C, nearly doubled survival time compared to standard chemotherapy in patients with advanced pancreatic cancer. If approved, this class of therapy could significantly change the treatment landscape for KRAS-driven cancers.
Advancing any of these programs depends on access to well-characterized KRAS proteins across multiple mutant variants. As research expands further into diverse variants and new modalities, having a reliable, comprehensive source of recombinant KRAS protein is more important than ever.
Amid Biosciences’ KRAS Protein Portfolio
Whether you are running biochemical binding assays, developing KRAS-targeted PROTACs, profiling nucleotide exchange kinetics, or screening inhibitor libraries, having access to well-characterized, high-purity recombinant KRAS protein is essential. Amid Biosciences offers both biotinylated and non-biotinylated variants of the mutations most relevant to current drug discovery campaigns.
| Protein | Format | Key Cancer Indication | Research Use |
|---|---|---|---|
| KRAS Wild-Type |
BIOTINYLATED, NON-BIOTINYLATED |
Reference / Selectivity control |
Baseline binding assays, selectivity profiling |
| KRAS G12C |
BIOTINYLATED NON-BIOTINYLATED |
NSCLC, colorectal | Covalent inhibitor screening, SPR, ITC |
| KRAS G12D |
BIOTINYLATED NON-BIOTINYLATED |
Pancreatic, colorectal, NSCLC |
Non-covalent inhibitor discovery, PROTAC development |
| KRAS G12R |
BIOTINYLATED NON-BIOTINYLATED |
Pancreatic cancer | Biochemical assays, effector interaction studies |
| KRAS Q61H |
BIOTINYLATED NON-BIOTINYLATED |
Melanoma, colorectal |
GTPase activity assays, resistance mechanism studies |
All KRAS proteins are produced as isoform KRAS4B, the predominant isoform in most tumor types, with an N-terminal or C-terminal AviTag™ and His-tag for flexible downstream applications. Each lot undergoes rigorous quality control to confirm purity, identity, and assay suitability before shipment.
Custom Nucleotide Loading Service
Amid Biosciences also offers custom loading of KRAS proteins with nucleotides or their analogs - including GDP, GTP, GMPPNP, and GMPPCP. This service is invaluable for researchers studying the conformational states that govern inhibitor binding, or for setting up functional assays that require KRAS in a defined nucleotide state. Simply contact the team at info@amidbiosciences.com to discuss your requirements.
The KRAS Signaling Ecosystem: Beyond the Protein Itself
Understanding KRAS effector binding is central to characterizing inhibitor mechanisms of action. Drug discovery recognizes that KRAS doesn't act alone. Guanine nucleotide exchange factors (GEFs) that activate KRAS and GAPs (GTPase-activating proteins) that deactivate it are emerging as targets in their own right. Amid Biosciences also provides key KRAS-interacting biomolecules to support this systems-level view:
| Target/Effector | Description/Function |
|---|---|
| SOS1 | GEF that catalyzes GDP→GTP exchange; target for allosteric KRAS inhibitors like BI-3406. |
| NF1 (Neurofibromin) | Major KRAS GAP; loss-of-function mutations drive resistance to KRAS G12C inhibitors. |
|
RAF1-RBD RAF1-RBD (biotinylated) |
RAS-binding domain of Raf1; widely used in effector pulldown and competition binding assays. |
|
PI3Kα-RBD (biotinylated) PI3Kα-RBD (GST-tag) |
Measures PI3K pathway engagement; critical for combination therapy research. |
| SHP2 | Phosphatase upstream of RAS activation; SHP2 inhibitors are in clinical trials in combination with KRAS inhibitors. |
|
MEK1 MEK2 |
Downstream MAPK effectors; essential for pathway profiling and resistance studies. |
Additionally, we offer Cyclophilin A (CypA)–KRAS Protein Kits
These kits facilitate the discovery of novel inhibitors targeting "undruggable" KRAS mutations, such as G12D and G12V, by leveraging the chaperone protein cyclophilin A (CypA).
The Cyclophilin A – KRAS G12D Protein Kit (Catalog # KR12DCP-301) includes:
- Recombinant biotinylated human G12D KRAS (1-185) Protein – 0.05 mg
- Recombinant biotinylated human wild-type KRAS (1-185) Protein – 0.05 mg
- Recombinant human Cyclophilin A (CypA) – 0.1 mg
The Cyclophilin A – KRAS G12V Protein Kit (Catalog # KR12VCP-301) includes:
- Recombinant biotinylated human G12V KRAS (1-185) Protein – 0.05 mg
- Recombinant biotinylated human wild-type KRAS (1-185) Protein – 0.05 mg
- Recombinant human Cyclophilin A (CypA) – 0.1 mg
KRAS has historically been considered "undruggable" due to its smooth surface, which lacks conventional drug binding sites. Molecular glues address this challenge by inducing interactions between KRAS and other proteins to inhibit cancer signaling. Utilizing this approach, the kit enables research similar to methods employed by Revolution Medicines, where an inhibitor binds to CypA to form a complex that selectively targets and shuts down mutant RAS.
Amid Biosciences also offers custom kit construction to meet specific customer requirements.
Choosing the Right KRAS Protein for Your Assay
Surface Plasmon Resonance & BLI Binding Assays
For label-free binding kinetics, biotinylated KRAS proteins are ideal for capture on streptavidin biosensor chips or tips. Amid Biosciences’ site-specifically biotinylated variants ensure uniform orientation - critical for accurate KD determination - and support more consistent immobilization than random chemical biotinylation, which can modify lysines near functionally relevant surfaces and may interfere with binding in some assay formats.
HTRF / TR-FRET Competitive Binding Assays
High-throughput screening campaigns commonly employ HTRF formats using biotinylated KRAS captured on streptavidin-XL665, paired with a labeled Raf1-RBD or antibody. Amid Biosciences’ biotinylated KRAS G12C and G12D are well-suited to this format and have been used successfully in inhibitor triage workflows.
Biochemical GTPase & Nucleotide Exchange Assays
Intrinsic GTPase assays and SOS1-catalyzed nucleotide exchange assays require KRAS loaded with defined nucleotides. Amid Biosciences’ nucleotide-loading service, combined with their high-purity recombinant SOS1, provides a complete toolkit for mechanistic characterization of KRAS modulators.
Why Researchers Choose Amid Biosciences
US-made: Manufactured in Santa Clara, CA. No import delays, no supply chain uncertainty.
Competitive pricing: Lean supply chain model passes savings to researchers - starting at $500.00/0.1 mg (biotinylated) - without compromising quality.
NEXT-DAY SHIPPING: Order before 2:30 PM PST and your KRAS protein ships the same day.
PhD scientist support: Technical support from scientists who understand your assay, not a call center.
References
- https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sotorasib-panitumumab-kras-g12c-mutated-colorectal-cancer
- https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-adagrasib-cetuximab-kras-g12c-mutated-colorectal-cancer
- https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-combination-avutometinib-and-defactinib-kras-mutated-recurrent-low
- A pan-KRAS inhibitor and its derived degrader elicit multifaceted anti-tumor efficacy in KRAS-driven cancers. Juanjuan Feng et al, Cancer Cell, Volume 43, Issue 10, 13 October 2025, Pages 1866-1884.e12 https://www.sciencedirect.com/science/article/pii/S1535610825003101
- Breaking down KRAS: small-molecule degraders for cancer therapy. Tina Kos, Dieter Saur, Signal Transduct Target Ther. 2025 Mar 14;10:86. doi: 10.1038/s41392-025-02172-4 https://pmc.ncbi.nlm.nih.gov/articles/PMC11906874/
- Targeting KRAS. Anupriya Singhal, Bob T. Li, Eileen M. O’Reilly Nat Med. 2024 April; 30(4): 969–983. doi:10.1038/s41591-024-02903-0.https://pmc.ncbi.nlm.nih.gov/articles/PMC11845254/