| Identification | Back Directory | [Name]
JNJ-7706621 | [CAS]
443797-96-4 | [Synonyms]
CS-409
JNJ-7706621 USP/EP/BP
JNJ7706621; JNJ 7706621
Aurora Kinase/Cdk Inhibitor
Aurora Kinase/Cdk Inhibitor - CAS 443797-96-4 - Calbiochem
4-[[5-Amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide
4-[[5-Amino-1-(2,6-difluorobenzoyl)-1H-1,2,4-triazol-3-yl]amino]benzenesulfonamide
Benzenesulfonamide, 4-[[5-amino-1-(2,6-difluorobenzoyl)-1H-1,2,4-triazol-3-yl]amino]-
4-[[5-Amino-1-(2,6-difluorobenzoyl)-1H-1,2,4-triazol-3-yl]amino]benzenesulfonamide JNJ7706621 | [Molecular Formula]
C15H12F2N6O3S | [MDL Number]
MFCD11100270 | [MOL File]
443797-96-4.mol | [Molecular Weight]
394.36 |
| Chemical Properties | Back Directory | [Melting point ]
149-155℃ | [Boiling point ]
676.6±65.0 °C(Predicted) | [density ]
1.71 | [storage temp. ]
+2C to +8C | [solubility ]
Soluble in DMSO at 15mg/ml | [form ]
White solid | [pka]
9.80±0.12(Predicted) | [color ]
White to off-white | [Sensitive ]
Light Sensitive | [InChI]
1S/C15H12F2N6O3S/c16-10-2-1-3-11(17)12(10)13(24)23-14(18)21-15(22-23)20-8-4-6-9(7-5-8)27(19,25)26/h1-7H,(H2,19,25,26)(H3,18,20,21,22) | [InChIKey]
KDKUVYLMPJIGKA-UHFFFAOYSA-N | [SMILES]
Fc1c(c(ccc1)F)C(=O)N2NC(=NC2=N)Nc3ccc(cc3)[S](=O)(=O)N |
| Hazard Information | Back Directory | [Description]
JNJ-7706621 is a dual inhibitor of cyclin-dependent kinases (CDKs) and Aurora kinases. It potently inhibits Cdk1/cyclin B, Cdk2/cyclin A, Cdk2/cyclin E, Cdk3/cyclin E, Cdk4/cyclin D1, Cdk6/cyclin D1, Aurora A, and Aurora B in vitro (IC50s = 9, 4, 3, 58, 253, 175, 11, and 15 nM, respectively).1 It shows selectivity for these enzymes over a panel of other receptors and kinases, although it exhibits submicromolar inhibition of VEGF and FGF receptors, as well as GSK3β.1 JNJ-7706621 blocks the growth of a large variety of cancer cell lines (IC50 values range from 112 to 514 nM), with lower potency against normal cells (IC50 values between 3.67 and 5.42 μM). It induces the regression of A375 melanoma human tumor xenografts in mice.1 JNJ-7706621 is a substrate for the ATP-binding cassette transporter G2, also known as breast cancer resistance protein.2 | [Uses]
JNJ-770662 is a broad spectrum inhibitor of cyclin-dependent kinases and aurora kinases including CDK1/Cyclin B, CDK2/Cyclin A, CDK2/Cyclin E, Aurora-A and Aurora-B. JNJ-770662 has been shown to induce growth suppression and mitotic defects, these results suggest that JNJ-7706621 could be useful for cell cycle analysis and therapy of various cancers, including Ewing''s sarcoma. | [Definition]
ChEBI: 4-[[5-amino-1-[(2,6-difluorophenyl)-oxomethyl]-1,2,4-triazol-3-yl]amino]benzenesulfonamide is a sulfonamide. | [Synthesis]
The general procedure for the synthesis of 4-[[5-amino-1-(2,6-difluorobenzoyl)-1H-1,2,4-triazol-3-yl]amino]benzenesulfonamides from 2,6-difluorobenzohydrazide and N-[4-(aminosulfonyl)phenyl]-N'-cyanocarbamoyl phenyl ester (CAS: 700805-72-7) was as follows: a series of experiments were carried out to examine solvent and base effects on the yield of the target product as determined by HPLC. The experiments were performed as follows: N-[4-(aminosulfonyl)phenyl]-N'-cyanocarbamic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6-difluorobenzoyl hydrazine (0.3 g, 1.74 mmol) were dissolved in 15 mL of the solvent of choice, and the base of choice was added with stirring (2.08 mmol, 1.3 eq., see Table 4). The reaction mixture was heated to 80-85 °C and maintained at this temperature for 6 hours. After completion of the reaction, the mixture was cooled to 20-25 °C and sampled for HPLC analysis.The HPLC samples were prepared by diluting aliquots with acetonitrile and water (50/50) to determine the percentage conversion to 4-[[5-amino-1-(2,6-difluorobenzoyl)-1H-1,2,4-triazol-3-yl]amino]benzenesulphonamide and the results are presented in Table 4. Table 4: Effect of solvent and base on the yield of the target producta,b. Different amounts of isourea exchange product and decomposition were observed in all cases, except for the case where pyridine was used.c. HPLC analysis showed c-3% of the other regional isomer.d. HPLC analysis showed ~1.4% of the other regional isomer.e. The results are presented in Table 4. | [in vivo]
JNJ-7706621 (100 and 125 mg/kg) is efficacious in a human tumor xenograft model under intermittent dosing regimens[3]. JNJ-7706621 (100 mg/kg, i.p.) exhibits 95% tumor growth inhibition in A375 (human melanoma) tumor xenograft model[1]. JNJ-7706621-loaded micelles inhibit tumor growth, and delay the tumor growth more efficiently than the control JNJ-7706621 suspension[4]. | [target]
CDK1 | [IC 50]
CDK6/cyclinD1: 175 nM (IC50); CDK2/cyclinE: 3 nM (IC50); Cdk4/cyclin D1: 253 nM (IC50); Cdk1/cyclin B: 9 nM (IC50); cdk2/cyclin A: 4 nM (IC50); CDK3/Cyclin E: 58 nM (IC50); Aurora A: 11 nM (IC50); Aurora B: 15 nM (IC50); VEGF-R2: 154 nM (IC50); VEGF-R1: 6400 nM (IC50); VEGF-R3: 735 nM (IC50); FGF-R1: 575 nM (IC50); FGF-R2: 226 nM (IC50); GSK3β: 254 nM (IC50) | [References]
[1] Patent: WO2005/77922, 2005, A2. Location in patent: Page/Page column 46
[2] Patent: WO2005/77922, 2005, A2. Location in patent: Page/Page column 48-49
[3] Patent: WO2005/77922, 2005, A2. Location in patent: Page/Page column 54-55
[4] Patent: WO2005/77922, 2005, A2. Location in patent: Page/Page column 50-51
[5] Patent: WO2005/77922, 2005, A2. Location in patent: Page/Page column 50-51 |
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| Company Name: |
J & K SCIENTIFIC LTD.
|
| Telephone: |
18210857532 18210857532 |
| Website: |
https://www.jkchemical.com |
| Company Name: |
NCE Biomedical Co.,Ltd.
|
| Telephone: |
4000-027-021 |24 +86-13986109188 | +86-15623472865 | +81-08033611988 |
| Website: |
www.chemicalbook.com/ShowSupplierProductsList15748/0_EN.htm |
| Company Name: |
LETOPHARM LIMITED
|
| Telephone: |
+86-21-5821 5861 |
| Website: |
www.letopharm.com |
|