(R)-G12Di-7 is a covalent ligand of KRAS-G12D that selectively labels K-Ras-G12D·GDP and K-Ras-G12D·GppNHp. (R)-G12Di-7 has inhibitory activity against G12D mutant cancer cells.

Physicochemical Properties

Molecular Formula	C39H37F3N6O5
Molecular Weight	726.74
CAS #	2946593-60-6
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	(R)-G12Di-7 (1-100 nM) inhibits cell viability of KRAS-G12D mutant cells Ba/F3, SW1990, AsPC-1 and AGS with GI50 values of 73 nM, 409 nM, 467 nM and 109 nM, respectively[1]. (R)-G12Di-7 (10 μM) labels KRAS-G12D in G12D mutant cells Ba/F3, SW1990, AsPC-1 and AGS, thereby inhibiting downstream signaling and maintaining stability within 12 hours[1].
ln Vivo	(R)-G12Di-7 (10-50 mg/kg, intraperitoneally, twice a day for 28 days) has antitumor activity in SW1900 xenografted NOD/SCID mice [1].
Cell Assay	Cell Viability Assay[1] Cell Types: Ba/F3, SW1990, AsPC-1, AGS Tested Tested Concentrations: 1-1000 nM Incubation Duration: 72 h Experimental Results: Inhibited cell growth of Ba/F3, SW1990, AsPC-1 and AGS. Western Blot Analysis[1] Cell Types: Ba/F3, SW1990, AsPC-1, AGS Tested Tested Concentrations: 10 μM Incubation Duration: 4 h Experimental Results: Suppressed expression K-RAS-G12D and phosphorylation of ERK and Akt in cells G12D mutated cells Ba/F3, SW1990, AsPC-1 and AGS.
Animal Protocol	Animal/Disease Models: SW1900 xenograft NOD/SCID mice[1] Doses: 10-50 mg/kg Route of Administration: i.p., twice a day for 28 days Experimental Results: Inhibited tumor growth and weight loss.
References	[1]. Strain-release alkylation of Asp12 enables mutant selective targeting of K-Ras-G12D. Nat Chem Biol. 2024 Mar 5.

Solubility Data

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.3760 mL	6.8800 mL	13.7601 mL
	5 mM	0.2752 mL	1.3760 mL	2.7520 mL
	10 mM	0.1376 mL	0.6880 mL	1.3760 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.