| Identification | Back Directory | [Name]
BLU 9931 | [CAS]
1538604-68-0 | [Synonyms]
BLU
CS-1699
BLU9931
LM-3610
BLU-9931
BLU 9931
LM-3610; BLU9931
BLU 9931;BLU-9931
BLU-9931;BLU 9931;BLU9931
BLU9931, 98%, a potent, selective, and irreversible FGFR4 inhibitor
N-(2-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)-3-methylphenyl)acrylamide
N-[2-[[6-(2,6-Dichloro-3,5-dimethoxyphenyl)-2-quinazolinyl]amino]-3-methylphenyl]-2-propenamide
2-Propenamide,N-[2-[[6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-quinazolinyl]amino]-3-methylphenyl]- | [Molecular Formula]
C26H22Cl2N4O3 | [MDL Number]
MFCD28900729 | [MOL File]
1538604-68-0.mol | [Molecular Weight]
509.38 |
| Chemical Properties | Back Directory | [density ]
1.361±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
≥50.9 mg/mL in DMSO; insoluble in H2O; ≥2.53 mg/mL in EtOH with gentle warming and ultrasonic | [form ]
Powder | [pka]
13.15±0.70(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Uses]
BLU9931 is a potent, highly selective, and irreversible fibroblast growth factor receptor 4 (FGFR4) inhibitor with an IC50 of 3 nM and a Kd of 6 nM. BLU9931 has significant antitumor activity[1]. | [Definition]
BLU9931 is a potent, highly selective, and irreversible fibroblast growth factor receptor 4 (FGFR4) inhibitor with an IC50 of 3 nM and a Kd of 6 nM. BLU9931 has significant antitumor activity. BLU9931 makes a covalent bond with Cys552 within the ATP-binding pocket of FGFR4, which is not present in FGFR1-3. BLU9931 inhibited gastric cancer cell growth in a transplanted mouse model[1].
| [Synthesis]
The general procedure for the synthesis of N-[2-[[6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-quinazolinyl]amino]-3-methylphenyl]-2-acrylamide from the compound (CAS: 1538605-10-5) and acryloyl chloride was performed as follows: the N'-[6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl]- 6-methylbenzene-1,2-diamine (5.16 g, 11.33 mmol) was dissolved in dichloromethane (DCM, 100 mL) and cooled to 0 °C. Subsequently, N,N-diisopropylethylamine (DIEA, 1.781 mL, 10.20 mmol) and acryloyl chloride (1.013 mL, 12.47 mmol) were sequentially added at 0 °C and the reaction mixture was stirred for 2 h at this temperature. After completion of the reaction, the mixture was directly sampled onto a silica gel column and purified by fast column chromatography using 0-100% ethyl acetate (EtOAc)/hexane gradient elution. Finally, the target product N-[2-[[6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-quinazolinyl]amino]-3-methylphenyl]-2-propenamide was obtained as an off-white solid (3.5 g, 61% yield). The mass spectrum (electrospray positive ion mode, ES+) showed the molecular ion peak m/z 509 [M+H]+, which is consistent with the calculated value of the molecular formula C26H22Cl2N4O3.1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.23 (s, 1H), 8.68 (s, 1H), 7.82-7.65 (m, 2H) , 7.51 (s, 2H), 7.21 (m, 1H), 7.12 (d, J = 6.8 Hz, 1H), 7.01 (s, 1H), 6.49 (dd, J = 17.0, 10.2 Hz, 1H), 6.28-6.15 (m, 1H), 5.68 (dd, J = 10.2, 2.0 Hz, 1H), 3.97 (s, 6H) , 2.19 (s, 3H). | [in vivo]
BLU9931 (10-100 mg/kg; oral administration; twice every day; for 21 days; mice) treatment demonstrates antitumor activity in HCC xenograft models[1]. | Animal Model: | Mice injected with Hep 3B cells[1] | | Dosage: | 10 mg/kg, 30 mg/kg or 100 mg/kg | | Administration: | Oral administration; twice every day; for 21 days | | Result: | Resulted in dose-dependent growth inhibition of Hep 3B tumors. Prevented weight loss in a dose-dependent manner.
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| [IC 50]
FGFR1: 591 nM (IC50); FGFR2: 493 nM (IC50); FGFR3: 150 nM (IC50); FGFR4: 3 nM (IC50) | [References]
[1] Norihiko Sasaki. “FGFR4 Inhibitor BLU9931 Attenuates Pancreatic Cancer Cell Proliferation and Invasion While Inducing Senescence: Evidence for Senolytic Therapy Potential in Pancreatic Cancer.” Cancers (2020).
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