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
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 |
mg/mL |
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 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
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.
