Synonym
Kobe2602; Kobe 2602; Kobe-2602
IUPAC/Chemical Name
2-(2,6-dinitro-4-(trifluoromethyl)phenyl)-N-(4-fluorophenyl)hydrazinecarbothioamide
InChi Key
NNPBSITXCGPXJC-UHFFFAOYSA-N
InChi Code
InChI=1S/C14H9F4N5O4S/c15-8-1-3-9(4-2-8)19-13(28)21-20-12-10(22(24)25)5-7(14(16,17)18)6-11(12)23(26)27/h1-6,20H,(H2,19,21,28)
SMILES Code
FC(C1=CC([N+]([O-])=O)=C(NNC(NC2=CC=C(F)C=C2)=S)C([N+]([O-])=O)=C1)(F)F
Appearance
Light yellow 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:
Kobe2602 is a Ras-Raf interaction inhibitor that inhibits the binding of H-Ras·GTP to c-Raf-1 RBD with a Ki of 149 μM.
In vitro activity:
The effect of the compounds on the cellular activity of Raf, which is dependent on its interaction with Ras⋅GTP. Both Kobe0065 and Kobe2602 at 20 μM efficiently inhibited the phosphorylation of MEK and ERK, downstream kinases of Raf in NIH 3T3 cells transiently expressing H-RasG12V. The effect of Kobe0065 and Kobe2602 was next tested on anchorage-independent proliferation of H-rasG12V–transformed NIH 3T3 cells. The compounds efficiently inhibited colony formation in soft agar in a dose-dependent manner (Fig. 3A and Fig. S3A). The IC50 values were around 0.5 and 1.4 μM for Kobe0065 (Fig. 3B) and Kobe2602 (Fig. S3B), respectively, which were comparable to the value of 2.1 μM observed for sorafenib (Fig. S3B). By contrast, the compounds failed to inhibit colony formation of NIH 3T3 cells transformed by the activated c-raf-1 gene carrying the S259A/Y340D/Y341D mutations (Fig. 3C and Fig. S4A.).
Reference: Proc Natl Acad Sci U S A. 2013 May 14; 110(20): 8182–8187. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657810/
In vivo activity:
The antitumor activity of the Kobe2602 was assessed by using a xenograft of SW480 cells in nude mice. Daily oral administration of the compound at the dose of 80 mg/kg caused ∼40–50% inhibition of the tumor growth. During these compound treatments the mice did not exhibit any significant body weight loss (Fig. S5). Immunostaining of the tumor sections showed that the ERK activation was substantially compromised by the compound administration (Fig. 4B). Moreover, the compound-treated tumors showed a prominent increase of apoptotic cells (Fig. S6A), suggesting a contribution of the oncogene addiction mechanism to the antitumor effect.
Reference: Proc Natl Acad Sci U S A. 2013 May 14; 110(20): 8182–8187. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657810/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
39.0 |
93.01 |
|
| Ethanol |
23.0 |
54.85 |
|
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
419.31
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. 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. PMID: 23630290; PMCID: PMC3657810.
In vitro protocol:
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. PMID: 23630290; PMCID: PMC3657810.
In vivo protocol:
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. PMID: 23630290; PMCID: PMC3657810.
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.
2: Shima F, Yoshikawa Y, Matsumoto S, Kataoka T. Discovery of small-molecule Ras inhibitors that display antitumor activity by interfering with Ras·GTP-effector interaction. Enzymes. 2013;34 Pt. B:1-23. doi: 10.1016/B978-0-12-420146-0.00001-9. Epub 2013 Nov 7. Review. PubMed PMID: 25034098.
