WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406531
CAS#: 436133-68-5
Description: Kobe0065 is a small-molecule Ras inhibitors that display antitumor activity by blocking the Ras-effector interaction. Kobe0065 binds to Ras-GTP, blocking interactions with Raf kinase. Kobe0065 inhibits anchorage-dependent and -independent growth, blocks MEK/ERK activity and induces apoptosis in H-rasG12V transformed NIH3T3 cells. Kobe0065 also inhibits tumor growth in SW480 colon cancer cell xenografts.
MedKoo Cat#: 406531
Name: Kobe0065
CAS#: 436133-68-5
Chemical Formula: C15H11ClF3N5O4S
Exact Mass: 449.01724
Molecular Weight: 449.79
Elemental Analysis: C, 40.05; H, 2.46; Cl, 7.88; F, 12.67; N, 15.57; O, 14.23; S, 7.13
Synonym: Kobe0065; Kobe 0065; Kobe0065.
IUPAC/Chemical Name: N-(3-chloro-4-methylphenyl)-2-(2,6-dinitro-4-(trifluoromethyl)phenyl)hydrazinecarbothioamide.
InChi Key: KSJVAYBCXSURMQ-UHFFFAOYSA-N
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)
SMILES Code: FC(C1=CC([N+]([O-])=O)=C(NNC(NC2=CC=C(C)C(Cl)=C2)=S)C([N+]([O-])=O)=C1)(F)F
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Kobe0065 is an inhibitor of Ras-Raf interaction, competitively inhibiting the binding of H-Ras·GTP to c-Raf-1 RBD with a Ki value of 46±13 μM. |
| In vitro activity: | This study first examined the effect of Kobe0065, the most potent inhibitor among the Kobe0065-family compounds, on LOX (lysyl oxidase) expression in three human cancer cell lines, SW620 carrying the K-rasG12V, Panc-1 carrying the K-rasG12D and BxPC-3 carrying the wild-type ras in 2D culture. These cell lines showed high expression of 46-kDa prepro-LOX, which was effectively downregulated by treatment with 20 μM Kobe0065 in SW620 and Panc-1 but not BxPC-3 (Fig. 1A). Reference: Cancer Lett. 2017 Dec 1;410:82-91. https://pubmed.ncbi.nlm.nih.gov/28951129/ |
| In vivo activity: | The antitumour activity of GA (glycyrrhetinic acid) was assessed using a xenograft of A549 cells in nude mice. The tumour size of the model group displayed a significant increase compared with the GA-treated mice (Fig. 5A and B). A high dose of GA inhibited tumour growth by 50%–60%, similar to animals treated with Kobe (Kobe0065). For the histological analysis, tumour tissue sections were stained with haematoxylin & eosin (H&E). Compared with the model group, the high-dose GA and Kobe groups exhibited an obviously ameliorated severity of necrosis and pyknosis in the nuclei of tumour cells. Reference: Acta Pharm Sin B. 2019 Mar; 9(2): 294–303. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438844/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 50.5 | 112.27 | |
| DMSO:PBS (pH 7.2) (1:1) | 0.5 | 1.11 | |
| DMF | 10.0 | 22.23 | |
| Ethanol | 9.0 | 20.01 |
The following data is based on the product molecular weight 449.79 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Yoshikawa Y, Takano O, Kato I, Takahashi Y, Shima F, Kataoka T. Ras inhibitors display an anti-metastatic effect by downregulation of lysyl oxidase through inhibition of the Ras-PI3K-Akt-HIF-1α pathway. Cancer Lett. 2017 Dec 1;410:82-91. doi: 10.1016/j.canlet.2017.09.017. Epub 2017 Sep 23. PMID: 28951129. 2. Zhang Y, Wang Z, Ma X, Yang S, Hu X, Tao J, Hou Y, Bai G. Glycyrrhetinic acid binds to the conserved P-loop region and interferes with the interaction of RAS-effector proteins. Acta Pharm Sin B. 2019 Mar;9(2):294-303. doi: 10.1016/j.apsb.2018.11.002. Epub 2018 Nov 27. PMID: 30976491; PMCID: PMC6438844. |
| In vitro protocol: | 1. Yoshikawa Y, Takano O, Kato I, Takahashi Y, Shima F, Kataoka T. Ras inhibitors display an anti-metastatic effect by downregulation of lysyl oxidase through inhibition of the Ras-PI3K-Akt-HIF-1α pathway. Cancer Lett. 2017 Dec 1;410:82-91. doi: 10.1016/j.canlet.2017.09.017. Epub 2017 Sep 23. PMID: 28951129. |
| In vivo protocol: | 1. Zhang Y, Wang Z, Ma X, Yang S, Hu X, Tao J, Hou Y, Bai G. Glycyrrhetinic acid binds to the conserved P-loop region and interferes with the interaction of RAS-effector proteins. Acta Pharm Sin B. 2019 Mar;9(2):294-303. doi: 10.1016/j.apsb.2018.11.002. Epub 2018 Nov 27. PMID: 30976491; PMCID: PMC6438844. |
1: Shima F, Yoshikawa Y, Ye M, Araki M, Matsumoto S, Liao J, Hu L, Sugimoto T, Ijiri Y, Takeda A, Nishiyama Y, Sato C, Muraoka S, Tamura A, Osoda T, Tsuda K, Miyakawa T, Fukunishi H, Shimada J, Kumasaka T, Yamamoto M, Kataoka T. In silico discovery of small-molecule Ras inhibitors that display antitumor activity by blocking the Ras-effector interaction. Proc Natl Acad Sci U S A. 2013 May 14;110(20):8182-7. doi: 10.1073/pnas.1217730110. Epub 2013 Apr 29. PubMed PMID: 23630290; PubMed Central PMCID: PMC3657810.
