6H05 TFA (6H-05; 6 H05), the trifluoroacetic acd salt of 6H05, is a potent, covalent, selective and allosteric inhibitor of K-Ras (G12C) which is oncogenic. It might have antitumor properties. 6H05 inhibits and modifies the oncogenic KRAS G12C mutant allosterically.

Physicochemical Properties

Molecular Formula	C20H30CLN3O2S3
Molecular Weight	590.14
Exact Mass	589.111
Elemental Analysis	C, 44.78; H, 5.30; Cl, 6.01; F, 9.66; N, 7.12; O, 10.84; S, 16.30
CAS #	2061344-88-3
Related CAS #	6H05;1469338-01-9
PubChem CID	86208069
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	11
Heavy Atom Count	36
Complexity	581
Defined Atom Stereocenter Count	0
SMILES	ClC1C=CC(=CC=1)SCC(N1CCC(C(NCCSSCCN(C)C)=O)CC1)=O.FC(C(=O)O)(F)F
InChi Key	YNMYIJSFFJXIRV-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H30ClN3O2S3.C2HF3O2/c1-23(2)12-14-29-28-13-9-22-20(26)16-7-10-24(11-8-16)19(25)15-27-18-5-3-17(21)4-6-18;3-2(4,5)1(6)7/h3-6,16H,7-15H2,1-2H3,(H,22,26);(H,6,7)
Chemical Name	1-[2-(4-chlorophenyl)sulfanylacetyl]-N-[2-[2-(dimethylamino)ethyldisulfanyl]ethyl]piperidine-4-carboxamide;2,2,2-trifluoroacetic acid
Synonyms	6 H 05 TFA; 6 H 05 TFA salt; 6H05 TFA; 6H05 TFA salt; 6-H-05 TFA; 6-H-05 TFA salt; K-Ras(G12C) inhibitor 6H05
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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	6H05, which allosterically alters the highly homologous protein H-Ras'soncogenicG12C mutant while sparing the wild-type K-Ras, exhibits the highest degree of modification[1]. Moreover, 6H05 can be synthesized into another oncogenic K-Ras(G12C) inhibitor by using it as an intermediate.[2]
ln Vivo
Cell Assay	6H05 exhibits allele-specific impairment of K-Ras function, according to preliminary evaluation of 6H05 in lung cancer cell lines, although further chemical optimization of 6H05 is required to be evaluated in vivo[1]. More research is required to determine the specificity and effectiveness of 6H05 in vivo as well as how it affects the subcellular localization of other farnesylated GTPases.
Animal Protocol
References	[1]. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature. 2013 Nov 28;503(7477):548-51. [2]. Harnessing allostery: a novel approach to drug discovery. Med Res Rev. 2014 Nov;34(6):1242-85.

Solubility Data

Solubility (In Vitro)

DMSO: ~100 mg/mL (~169.5 mM) Water: ~100 mg/mL (~169.5 mM) Ethanol: ~100 mg/mL (~169.5 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	1.6945 mL	8.4726 mL	16.9451 mL
	5 mM	0.3389 mL	1.6945 mL	3.3890 mL
	10 mM	0.1695 mL	0.8473 mL	1.6945 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.