SIAIS178

未知

SIAIS178

S648459-5mg

5mg

≥99%

-20°C储存

超低温冰袋运输

SIAIS178 is a potent and selective BCR-ABL degrader based on PROTAC technology with an IC 50 of 24 nM. SIAIS178 causes effective degradation of BCR-ABL protein by recruiting Von Hippel-Lindau (VHL) E3 ubiquitin ligase. SIAIS178 has anticancer activity In Vitro SIAIS178 (1-100 nM; for 16 hours) significantly reduces the BCR-ABL protein levels in a concentration dependent manner. SIAIS178 significantly inhibits the phosphorylation of BCR-ABL and the substrates STAT5. SIAIS178 (1, 10, 100, 1000 nM) exerts significant antiproliferative activity in BCR-ABL driven CML cell lines. SIAIS178 retains potency and selectivity against the BCR-ABL driven cell lines. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: K562 cells Concentration: 1, 3, 10, 30, 100 nM Incubation Time: 16 hours Result: Significantly reduced the BCR-ABL protein levels in a concentration dependent manner. In Vivo SIAIS178 (ip; 5, 15, and 45 mg/kg; 12 days) attenuates tumor progression in a dose-dependent manner, as determined by serial volumetric measurement . SIAIS178 (iv or ip; 2 mg/kg; 24 hours) has T 1/2 of 3.82 and 12.35 hours and C max of 1165.2 nM and 30 nM for iv and ip, respectively . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: NOD/SCID mice with termed K562-Luc Dosage: 5, 15, and 45 mg/kg Administration: Ip; 12 days Result: Attenuated tumor progression in a dose-dependent manner, as determined by serial volumetric measurement. Animal Model: Female Wistar rats Dosage: 2 mg/kg (Pharmacokinetic Analysis) Administration: Iv or ip; 24 hours Result: Had T 1/2 of 3.82 and 12.35 hours and C max of 1165.2 nM and 30 nM for iv and ip, respectively. Form:Solid IC50& Target:VHL Bcr-Abl 24 nM (IC 50 )

SIAIS178 是一种基于 PROTAC 技术的强效、选择性 BCR-ABL 降解剂，其 IC 50 为 24 nM。SIAIS178 可通过招募 Von Hippel-Lindau (VHL) E3 泛素连接酶有效降解 BCR-ABL 蛋白。SIAIS178 具有抗癌活性

2376047-73-1

C50H62ClN11O6S2

1012.68 g/mol

139474625

CC1=C(C(=CC=C1)Cl)NC(=O)C2=CN=C(S2)NC3=CC(=NC(=N3)C)N4CCN(CC4)C(=O)CCCCCCC(=O)N[C@H](C(=O)N5C[C@@H](C[C@H]5C(=O)NCC6=CC=C(C=C6)C7=C(N=CS7)C)O)C(C)(C)C

N-(2-chloro-6-methylphenyl)-2-[[6-[4-[8-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-8-oxooctanoyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide

1S/C50H62ClN11O6S2/c1-30-12-11-13-36(51)43(30)59-47(67)38-27-53-49(70-38)57-39-25-40(56-32(3)55-39)60-20-22-61(23-21-60)42(65)15-10-8-7-9-14-41(64)58-45(50(4,5)6)48(68)62-28-35(63)24-37(62)46(66)52-26-33-16-18-34(19-17-33)44-31(2)54-29-69-44/h11-13,16-19,25,27,29,35,37,45,63H,7-10,14-15,20-24,26,28H2,1-6H3,(H,52,66)(H,58,64)(H,59,67)(H,53,55,56,57)/t35-,37+,45-/m1/s1

YGQREOJIRFCRKQ-ZIBKGDFVSA-N

CC1=C(C(=CC=C1)Cl)NC(=O)C2=CN=C(S2)NC3=CC(=NC(=N3)C)N4CCN(CC4)C(=O)CCCCCCC(=O)NC(C(=O)N5CC(CC5C(=O)NCC6=CC=C(C=C6)C7=C(N=CS7)C)O)C(C)(C)C

139474625

DMSO : 300 mg/mL (296.24 mM; Need ultrasonic)