K-Ras(G12C) inhibitor 12 is a co-valent and allosteric inhibitor of K-Ras G12C with potential antitumor activity. The mutated, oncogenic form of K-ras is known as KRAS G12C. K-Ras(G12C) inhibitor 12 functions by attaching itself to K-Ras(G12C) and joining forces with KRAS's 12C cysteine to form a covalent bond.

Physicochemical Properties

Molecular Formula	C15H17CLIN3O3
Molecular Weight	449.67
Exact Mass	449
Elemental Analysis	C, 40.07; H, 3.81; Cl, 7.88; I, 28.22; N, 9.34; O, 10.67
CAS #	1469337-95-8
Related CAS #	1469337-95-8
PubChem CID	73555129
Appearance	Off-white to light yellow solid powder
Density	1.736±0.06 g/cm3
Boiling Point	680.2±55.0 °C at 760 mmHg
Flash Point	365.2±31.5 °C
Vapour Pressure	0.0±2.2 mmHg at 25°C
Index of Refraction	1.674
LogP	2.84
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	23
Complexity	457
Defined Atom Stereocenter Count	0
SMILES	C=CC(N1CCN(C(CNC2=CC(I)=C(Cl)C=C2O)=O)CC1)=O
InChi Key	JFIFBWVNHLXJFY-UHFFFAOYSA-N
InChi Code	InChI=1S/C15H17ClIN3O3/c1-2-14(22)19-3-5-20(6-4-19)15(23)9-18-12-8-11(17)10(16)7-13(12)21/h2,7-8,18,21H,1,3-6,9H2
Chemical Name	1-[4-[2-(4-chloro-2-hydroxy-5-iodoanilino)acetyl]piperazin-1-yl]prop-2-en-1-one
Synonyms	K-Ras(G12C) inhibitor 12; K-Ras(G12C) inhibitor
HS Tariff Code	2934.99.9001
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

Targets	K-Ras(G12C)
ln Vitro	K-Ras(G12C) inhibitor 12 is a member of a class of small molecules that binds to the common oncogenic mutant K-Ras(G12C) in an irreversible manner, preventing K-Ras(G12C) interactions. Some of them cause G12C-containing cancer cell lines to become less viable and more susceptible to apoptosis.[1]
ln Vivo
Cell Assay	K-Ras(G12C) inhibitor 12, an extremely potent Ras inhibitor, has an EC50 value of 0.32 μM in H1792 cells.It does not interfere with the activity of wild-type Ras; instead, it irreversibly binds to an oncogenic mutant K-Ras(G12C). K-Ras(G12C)-mutant cells show higher apoptosis and decreased viability after treatment with K-Ras(G12C) inhibitor 12 in comparison to cells without this mutation.
Animal Protocol
References	[1]. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature. 2013 Nov 28;503(7477):548-551.

Solubility Data

Solubility (In Vitro)

DMSO: ~27 mg/mL (~60.0 mM) Water: <1 mg/mL Ethanol: <1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.67 mg/mL (3.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.67 mg/mL (3.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2239 mL	11.1193 mL	22.2385 mL
	5 mM	0.4448 mL	2.2239 mL	4.4477 mL
	10 mM	0.2224 mL	1.1119 mL	2.2239 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.