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| | SIAIS178 Basic information |
| Product Name: | SIAIS178 | | Synonyms: | SIAIS178;N-(2-chloro-6-methylphenyl)-2-({6-[4-(7-{[(2S)-1-[(2S,4R)-4-hydroxy-2-({[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}carbamoyl)pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl}heptanoyl)piperazin-1-yl]-2-methylpyrimidin-4-yl}amino)-1,3-thiazole-5-carboxamide;N-(2-Chloro-6-methylphenyl)-2-((6-(4-(8-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-8-oxooctanoyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide | | CAS: | 2376047-73-1 | | MF: | C50H62ClN11O6S2 | | MW: | 1012.68 | | EINECS: | | | Product Categories: | | | Mol File: | 2376047-73-1.mol |  |
| | SIAIS178 Chemical Properties |
| density | 1.335±0.06 g/cm3(Predicted) | | pka | 10.94±0.70(Predicted) | | form | Solid | | color | White to off-white |
| | SIAIS178 Usage And Synthesis |
| Description | SIAIS178 is a potent BCR-ABL Degrader. SIAIS178 induces proper interaction between BCR-ABL and VHL ligase leading to effective degradation of BCR-ABL protein, achieves significant growth inhibition of BCR-ABL+ leukemic cells in vitro, and induces substantial tumor regression against K562 xenograft tumors in vivo. In addition, SIAIS178 also degrades several clinically relevant resistance-conferring mutations. Our data indicate that SIAIS178 as efficacious BCR-ABL degrader warrants extensive further investigation for the treatment of BCR-ABL+ leukemia. | | Uses | SIAIS178 is a potent and selective BCR-ABL degrader based on PROTAC technology with an IC50 of 24 nM. SIAIS178 causes effective degradation of BCR-ABL protein by recruiting Von Hippel-Lindau (VHL) E3 ubiquitin ligase. SIAIS178 has anticancer activity[1]. | | 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 [1].
SIAIS178 (iv or ip; 2 mg/kg; 24 hours) has T1/2 of 3.82 and 12.35 hours and Cmax of 1165.2 nM and 30 nM for iv and ip, respectively[1].
| Animal Model: | NOD/SCID mice with termed K562-Luc[1] | | 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.
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| Animal Model: | Female Wistar rats[1] | | Dosage: | 2 mg/kg (Pharmacokinetic Analysis) | | Administration: | Iv or ip; 24 hours | | Result: | Had T1/2 of 3.82 and 12.35 hours and Cmax of 1165.2 nM and 30 nM for iv and ip, respectively.
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| | IC 50 | VHL; Bcr-Abl: 24 nM (IC50) | | References | [1] Zhao Q, et al. Discovery of SIAIS178 as an Effective BCR-ABL Degrader by Recruiting Von Hippel-Lindau (VHL) E3 Ubiquitin Ligase. J Med Chem. 2019 Oct 24;62(20):9281-9298. DOI:10.1021/acs.jmedchem.9b01264 |
| | SIAIS178 Preparation Products And Raw materials |
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