KRAS inhibitor-9 is a potent KRAS inhibitor (Kd=92 μM), preventing the formation of GTP-KRAS and the downstream activation of KRAS. KRAS inhibitor-9 binds to KRAS G12D, KRAS G12C and KRAS Q61H proteins with moderate binding affinity. KRAS inhibitor-9 causes G2/M cell cycle arrest and causes apoptosis. KRAS inhibitor-9 selectively suppresses the proliferation/growth of NSCLC cells with KRAS mutations but not of normal lung cells. KRAS inhibitor-9

Physicochemical Properties

Molecular Formula	C13H9CLN2S2
Molecular Weight	292.806958913803
Exact Mass	291.989
Elemental Analysis	C, 53.33; H, 3.10; Cl, 12.11; N, 9.57; S, 21.90
CAS #	300809-71-6
PubChem CID	667738
Appearance	White to off-white solid powder
Density	1.5±0.1 g/cm3
Boiling Point	492.4±55.0 °C at 760 mmHg
Flash Point	251.6±31.5 °C
Vapour Pressure	0.0±1.2 mmHg at 25°C
Index of Refraction	1.772
LogP	4.85
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	18
Complexity	292
Defined Atom Stereocenter Count	0
SMILES	ClC1C=C(C=CC=1SC1=NC2C=CC=CC=2S1)N
InChi Key	DTSNLMOLTVGCGZ-UHFFFAOYSA-N
InChi Code	InChI=1S/C13H9ClN2S2/c14-9-7-8(15)5-6-11(9)17-13-16-10-3-1-2-4-12(10)18-13/h1-7H,15H2
Chemical Name	4-(1,3-benzothiazol-2-ylsulfanyl)-3-chloroaniline
Synonyms	DUN 09716; DUN09716; DUN-09716
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

ln Vitro	KRAS inhibitor-9 had a moderate binding affinity of -5.38, -5.41, and -3.97 kcal/mol for KRASG12D, KRAS G12C, and KRAS Q61H protein, respectively[1]. KRAS inhibitor-9 (0-100 μM) exhibits strong inhibition selectivity in NSCLC cells with IC50s for H2122, H358, and H460 cells ranging from 39.56 to 66.02 μM (at 72 hours)[1]. KRAS inhibitor-9 (0-100 μM; 24 hours) inhibits the production of GTP-KRAS in H2122, H358, and H460 cells[1]. KRAS inhibitor-9 (25-100 μM; 48 hours) prevents the downstream signaling pathway of KRAS from being activated[1]. KRAS inhibitor-9 (0-100 μM; 24-72 hours) causes apoptosis and cell cycle arrest in NSCLC[1].
Cell Assay	Cell Line: H2122 (KRAS G12C), H358 (KRAS G12C) and H460 (KRAS Q61H) cell lines Concentration: 0, 25, 50, 100 μM Incubation Time: 24, 48, and 72 hours Result: Inhibited three NSCLC cell lines in a dose- and time-dependent manner, but not in normal lung fibroblast cell line CCD-19Lu.
References	[1]. Identification of a New Potent Inhibitor Targeting KRAS in Non-small Cell Lung Cancer Cells. Front Pharmacol. 2017;8:823. Published 2017 Nov 14.

Solubility Data

Solubility (In Vitro)

DMSO: ~250 mg/mL (~853.8 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (7.10 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 20.8 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 2: ≥ 2.08 mg/mL (7.10 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 20.8 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	3.4152 mL	17.0759 mL	34.1518 mL
	5 mM	0.6830 mL	3.4152 mL	6.8304 mL
	10 mM	0.3415 mL	1.7076 mL	3.4152 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.