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Purity: ≥98%
Kobe0065 (Kobe 0065) is novel and potent inhibitor of the H-Ras-cRaf1 interaction which exhibits potent activity to competitively inhibit the binding of H-Ras·GTP to c-Raf-1 RBD with a Ki value of 46 ± 13 μM. Kobe0065 is a compound screened out by an in silico screen method as a potent inhibitor of the Ras–Raf interaction. It showed favorite efficacy to inhibit the binding of M-Ras.GTP and H-Ras.GTP to the Ras-binding domain of c-Raf-1. Kobe0065 also dose-dependently inhibited the binding of H-RasG12V to c-Raf-1 in NIH 3T3 cells with a rough IC50 value of 10 μM. Besides that, 20 μM of Kobe0065 effectively suppressed the phosphorylation of down-stream kinases of Raf, including MEK and ERK. In NIH 3T3 cells transfected with H-rasG12V, Kobe0065 inhibited the colony formation with IC50 value of 0.5 μM.
| ln Vitro |
Compounds from the Kobe0065 family bind to Ras·GTP and show antiproliferative effects on cancer cells that have activated Ras oncogenes. It is possible that the compounds' greater potency at the cellular level is due to their rather broad binding specificity toward different Ras family small GTPases, as evidenced by their efficient inhibition of Ras·GTP's interaction with its multiple effectors, such as Raf, PI3K, and RalGDS, as well as a regulator/effector called Sos. In NIH3T3 cells transiently expressing H-RasG12V, the phosphorylation of downstream kinases MEK and ERK is efficiently inhibited by 20 μM Kobe0065 and Kobe2602[2].
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| ln Vivo |
Oral administration of Kobe0065 and Kobe2602 has been shown to have anticancer activity on a xenograft of human colon carcinoma SW480 cells containing the K-ras(G12V) gene[1].
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| References |
[1]. Shima, Fumi, et al. In silico discovery of small-molecule Ras inhibitors that display antitumor activity by blocking the Ras-effector interaction. Proceedings of the National Academy of Sciences of the United States of America (2013), 110(20), 8182-8187,
[2]. Shima F, et al. Discovery of small-molecule Ras inhibitors that display antitumor activity by interfering with Ras·GTP-effector interaction. Enzymes. 2013;34 Pt. B:1-23 |
| Molecular Formula |
C15H11CLF3N5O4S
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| Molecular Weight |
449.79
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| CAS # |
436133-68-5
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| Related CAS # |
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| SMILES |
ClC1C([H])=C(C([H])=C([H])C=1C([H])([H])[H])N([H])C(N([H])N([H])C1C(=C([H])C(C(F)(F)F)=C([H])C=1[N+](=O)[O-])[N+](=O)[O-])=S
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| InChi Key |
KSJVAYBCXSURMQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H11ClF3N5O4S/c1-7-2-3-9(6-10(7)16)20-14(29)22-21-13-11(23(25)26)4-8(15(17,18)19)5-12(13)24(27)28/h2-6,21H,1H3,(H2,20,22,29)
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| Chemical Name |
N-(3-chloro-4-methylphenyl)-2-(2,6-dinitro-4-(trifluoromethyl)phenyl)hydrazinecarbothioamide.
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.56 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2233 mL | 11.1163 mL | 22.2326 mL | |
| 5 mM | 0.4447 mL | 2.2233 mL | 4.4465 mL | |
| 10 mM | 0.2223 mL | 1.1116 mL | 2.2233 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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