K-Ras-IN-1 (formerly known as K-Ras-Inhibitor-1) is a novel small molecule K-Ras inhibitor that binds to K-Ras in a hydrophobic pocket that is occupied by Tyr-71 in the apo-Ras crystal structure, in other words, K-Ras-IN-1 binds directly to K-Ras between switch I and switch II and inhibit Sos-catalyzed K-Ras activation. It inhibits Sos-mediated nucleotide exchange by attaching to K-Ras and preventing Sos from binding. K-Ras-IN-1 serves as a platform for acquiring probe molecules that are helpful in clarifying novel understandings of Ras signaling and in identifying K-Ras inhibitors for the management of cancer.

Physicochemical Properties

Molecular Formula	C11H13NOS
Molecular Weight	207.29
Exact Mass	207.071
Elemental Analysis	C, 63.74; H, 6.32; N, 6.76; O, 7.72; S, 15.47
CAS #	84783-01-7
Related CAS #	84783-01-7
PubChem CID	551134
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Boiling Point	332.1±44.0 °C at 760 mmHg
Flash Point	154.7±28.4 °C
Vapour Pressure	0.0±0.7 mmHg at 25°C
Index of Refraction	1.668
LogP	2.06
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	1
Heavy Atom Count	14
Complexity	213
Defined Atom Stereocenter Count	0
SMILES	S=C(N1CCCC1)C1C(O)=CC=CC=1
InChi Key	QIKLOVZAPGSYNO-UHFFFAOYSA-N
InChi Code	InChI=1S/C11H13NOS/c13-10-6-2-1-5-9(10)11(14)12-7-3-4-8-12/h1-2,5-6,13H,3-4,7-8H2
Chemical Name	(2-hydroxyphenyl)-pyrrolidin-1-ylmethanethione
Synonyms	K-Ras-IN-1; K-Ras-IN1; K-Ras-IN 1; K-Ras Inhibitor-1; K-Ras Inhibitor 1
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
ln Vitro	In vitro activity: K-Ras-IN-1 is a brand-new small molecule K-Ras inhibitor that attaches itself to K-Ras in a hydrophobic pocket in the apo-Ras crystal structure that Tyr-71 occupies. To put it another way, K-Ras-IN-1 attaches itself to K-Ras directly between switch I and switch II, blocking Sos-catalyzed K-Ras activation. It inhibits Sos-mediated nucleotide exchange by attaching to K-Ras and preventing Sos from binding. K-Ras-IN-1 serves as a platform for acquiring probe molecules that are helpful in clarifying novel understandings of Ras signaling and in identifying K-Ras inhibitors for the management of cancer.
ln Vivo
Enzyme Assay	Compounds that blocked Sos-mediated nucleotide exchange were tested for their ability to investigate the functional effects of binding to K-Ras. In this experiment, BODIPY-GTP is swapped for unlabeled GDP, which is catalyzed by Sos and causes a rise in fluorescence.
Animal Protocol
References	[1]. J Chem Inf Model . 2014 Feb 24;54(2):530-8. [2]. Angew Chem Int Ed Engl . 2012 Jun 18;51(25):6140-3.

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 28 mg/mL Water: <1 mg/mL Ethanol: <1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.06 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 25.0 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: ≥ 2.5 mg/mL (12.06 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 25.0 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (12.06 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.8242 mL	24.1208 mL	48.2416 mL
	5 mM	0.9648 mL	4.8242 mL	9.6483 mL
	10 mM	0.4824 mL	2.4121 mL	4.8242 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.