| Identification | Back Directory | [Name]
RGB-286638 (free base) | [CAS]
784210-88-4 | [Synonyms]
CS-2607
CS-2608
RGB-286638 (free base)
RGB-286638;RGB 286638;RGB-286638
2,6-DIBROMO-9,10-DI(1-NAPHTHYL)ANTHRACENE
1-[3-[4-[[4-(2-methoxyethyl)piperazin-1-yl]methyl]phenyl]-4-oxo-1H-indeno[1,2-c]pyrazol-5-yl]-3-morpholin-4-ylurea
N-[1,4-Dihydro-3-[4-[[4-(2-methoxyethyl)-1-piperazinyl]methyl]phenyl]-4-oxoindeno[1,2-c]pyrazol-5-yl]-N'-4-morpholinylurea
Urea, N-[1,4-dihydro-3-[4-[[4-(2-methoxyethyl)-1-piperazinyl]methyl]phenyl]-4-oxoindeno[1,2-c]pyrazol-5-yl]-N'-4-morpholinyl- | [Molecular Formula]
C29H35N7O4 | [MOL File]
784210-88-4.mol | [Molecular Weight]
545.63 |
| Chemical Properties | Back Directory | [density ]
1.39±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMF: 3 mg/ml; DMSO: 10 mg/ml; DMSO:PBS (pH 7.2) (1:20): 0.05 mg/ml; Ethanol: Partially soluble | [form ]
Powder | [pka]
9.19±0.20(Predicted) | [color ]
Light yellow to green yellow |
| Hazard Information | Back Directory | [Uses]
RGB-286638 is a CDK inhibitor that inhibits the kinase activity of cyclin T1-CDK9, cyclin B1-CDK1, cyclin E-CDK2, cyclin D1-CDK4, cyclin E-CDK3, and p35-CDK5 with IC50s of 1, 2, 3, 4, 5 and 5 nM, respectively; also inhibits GSK-3β, TAK1, Jak2 and MEK1, with IC50s of 3, 5, 50, and 54 nM. | [in vivo]
Dose-finding studies with RGB-286638 identify 40 mg/kg/day IV treatment as the maximum tolerated dose in SCID mice. Five days IV treatment with RGB-286638 significantly suppresses MM tumor growth, with maximum TGI (%) noted at day 14 following end of treatment at 85.06% and 86.34% in the 30 mg/kg and 40 mg/kg treated cohorts respectively. The log10 cell kill (LCK Td: 4.5 days) is 1.6 for both treated groups. RGB-286638 treatment is also associated with improved survival, evidenced by first death at day 24 in controls versus day 43 in both treated groups. No toxic deaths occurred during this study: maximum percentage of body weight (BW) loss is observed on day 5 (8.4%) at 30 mg/kg dosage schedule, and on day 15 (9.9%) after 40 mg/kg dosing, with weight recovery in the following two weeks[1]. | [IC 50]
T1-CDK9: 1 nM (IC50); cyclin B1-CDK1: 2 nM (IC50); cyclin E-CDK2: 3 nM (IC50); cyclin D1-CDK4: 4 nM (IC50); cyclin E-CDK3: 5 nM (IC50); p35-CDK5: 5 nM (IC50); cyclin H-CDK7: 44 nM (IC50); cyclin D3-CDK6: 55 nM (IC50); GSK-3β: 3 nM (IC50); JAK2: 50 nM (IC50); MEK1: 54 nM (IC50); Fms: 1 nM (IC50); TAK1: 5 nM (IC50); JNK1a1: 17 nM (IC50); JNK1a2: 40 nM (IC50); C-src: 25 nM (IC50); AMPK: 41 nM (IC50) | [References]
[1] Cirstea D, et al. Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia. 2013 Dec;27(12):2366-75. DOI:10.1038/leu.2013.194 |
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| Company Name: |
SPIRO PHARMA
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| Tel: |
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| Website: |
www.spiropharma.com.cn |
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