K-Ras (G12C) inhibitor 6 is a novel, potent, allosteric, irreversible,/covalent cysteine-reactive small molecule KRAS G12C inhibitor with anticancer activity. KRAS G12C is 100% modifiable and carcinogenic when applied at 10 µM for a full day in an in vitro setting. With a relative potency value of 4.2, it binds irreversibly to the GTPase K-Ras G12C mutantion but not to the wild-type K-Ras. The binding pocket of K-Ras for K-Ras (G12C) inhibitor 6 is a new allosteric pocket, S-IIP. Binding this pocket causes Ras's relative nucleotide affinity to shift in favor of GDP over GTP, which accumulates inactive Ras.

Physicochemical Properties

Molecular Formula	C17H22CL2N2O3S
Molecular Weight	405.34
Exact Mass	404.072
Elemental Analysis	C, 50.37; H, 5.47; Cl, 17.49; N, 6.91; O, 11.84; S, 7.91
CAS #	2060530-16-5
Related CAS #	2060530-16-5
PubChem CID	71815954
Appearance	Solid powder
Density	1.3±0.1 g/cm3
Boiling Point	643.4±55.0 °C at 760 mmHg
Flash Point	342.9±31.5 °C
Vapour Pressure	0.0±1.9 mmHg at 25°C
Index of Refraction	1.594
LogP	2.49
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	7
Heavy Atom Count	25
Complexity	448
Defined Atom Stereocenter Count	0
SMILES	ClC1C=C(C=CC=1OCC(N1CCC(CC1)NC(CCCS)=O)=O)Cl
InChi Key	ZPXCEHMKUTXHRZ-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H22Cl2N2O3S/c18-12-3-4-15(14(19)10-12)24-11-17(23)21-7-5-13(6-8-21)20-16(22)2-1-9-25/h3-4,10,13,25H,1-2,5-9,11H2,(H,20,22)
Chemical Name	N-[1-[2-(2,4-dichlorophenoxy)acetyl]piperidin-4-yl]-4-sulfanylbutanamide
Synonyms	MDK30165; K-Ras(G12C) Inhibitor 6; MDK-30165; MDK 30165
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	In vitro activity: K-Ras(G12C) inhibitor 6 is a member of a class of small molecules that binds to the common oncogenic mutant K-Ras(G12C) in an irreversible way, 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	The inhibitor of K-Ras G12C should have suppressive effects on tumor cells because K-Ras mutations are frequently found in human cancers. It's been documented that certain K-Ras G12C inhibitors work well to make lung cancer cell lines more apoptotic and less viable.
Animal Protocol
References	[1]. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature. 2013 Nov 28;503(7477):548-51.
Additional Infomation	See also: K-Ras(G12C) inhibitor 6 (annotation moved to).

Solubility Data

Solubility (In Vitro)

DMSO: ~81 mg/mL (~199.8 mM) Water: <1 mg/mL Ethanol: ~30 mg/mL (~74.0 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4671 mL	12.3353 mL	24.6706 mL
	5 mM	0.4934 mL	2.4671 mL	4.9341 mL
	10 mM	0.2467 mL	1.2335 mL	2.4671 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.