Kobe-2602 | CAS#454453-49-7 | RAS inhibitor

MedKoo Cat#: 406580 | Name: Kobe-2602

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Kobe2602 is an analog of Kobe0065 and a potent and selective RAS inhibitor, which exhibit inhibitory activity toward H-Ras GTP-c-Raf-1 binding both in vivo and in vitro. Kobe2602 effectively inhibits both anchorage-dependent and -independent growth and induces apoptosis of H-ras(G12V)-transformed NIH 3T3 cells, which is accompanied by down-regulation of downstream molecules such as MEK/ERK, Akt, and RalA as well as an upstream molecule, son of sevenless. Moreover, Kobe2602 exhibits antitumor activity on a xenograft of human colon carcinoma SW480 cells carrying the K-ras(G12V) gene by oral administration. Kobe2602 may serve as a scaffold for the development of Ras inhibitors with higher potency and specificity.

Chemical Structure

Kobe-2602

CAS#454453-49-7

Theoretical Analysis

MedKoo Cat#: 406580

Name: Kobe-2602

CAS#: 454453-49-7

Chemical Formula: C14H9F4N5O4S

Exact Mass: 419.0311

Molecular Weight: 419.31

Elemental Analysis: C, 40.10; H, 2.16; F, 18.12; N, 16.70; O, 15.26; S, 7.65

Price and Availability

Size	Price	Availability
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,250.00	Ready to ship
1g	USD 2,050.00	2 Weeks

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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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#CRB50209

QC Data

View QC data: current batch, Lot#CRB50209

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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
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:

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. 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 RasÂ·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.