SIAIS178

Size	Price	Stock	Quantity
--	$--	In stock

Size

Price

Stock

Quantity

$--

In stock

Purity

≥99%

Solubility

Soluble in DMSO (300 mg/mL, 296.24 mM, Need ultrasonic)

Appearance

Solid Powder

Storage

Store at 2-8°C for short term (days to weeks) or -20°C for long term (months to years)

IUPACName

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

Synonyms

SIAIS 178; SIAIS-178; N-(2-Chloro-6-methylphenyl)-2-((6-(4-(8-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methyl-thiazol-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; N-(8-{4-[6-({5-[(2-Chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl}amino)-2-methyl-4-pyrimidinyl]-1-piperazinyl}-8-oxooctanoyl)-3-methyl-L-valyl-(4R)-4-hydroxy-N-[4-(4-methyl-1,3-thiazol-5-yl)benzyl]-L-prolinamide

Density

1.335±0.06 g/cm3

InChI Key

YGQREOJIRFCRKQ-ZIBKGDFVSA-N

InChI

InChI=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

Canonical SMILES

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

1. Discovery of SIAIS178 as an Effective BCR-ABL Degrader by Recruiting Von Hippel-Lindau (VHL) E3 Ubiquitin Ligase

Yubao Shao, Quanju Zhao, Chaowei Ren, Renhong Sun, Xinyu Ding, Bei Yang, Ying Kong, Xianfang Zhang, Youwei Xu, Biao Jiang, Xiaobao Yang, Jinju Chen, Ning Sun, Qianqian Yin, Linyi Liu J Med Chem . 2019 Oct 24;62(20):9281-9298. doi: 10.1021/acs.jmedchem.9b01264.

The oncogenic fusion protein BCR-ABL is the driving force of leukemogenesis in chronic myeloid leukemia (CML). Despite great progress for CML treatment through application of tyrosine kinase inhibitors (TKIs) against BCR-ABL, long-term drug administration and clinical resistance continue to be an issue. Herein, we described the design, synthesis, and evaluation of novel proteolysis-targeting chimeric (PROTAC) small molecules targeting BCR-ABL which connect dasatinib and VHL E3 ubiquitin ligase ligand by extensive optimization of linkers. Our efforts have yielded SIAIS178 (19), which 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.

Good afternoon, what is the mechanism of action of SIAIS178?

SIAIS178 utilizes a technology called PROTAC (proteolysis targeting chimera). It functions as a "molecular glue," linking BCR-ABL to E3 ubiquitin ligases, cellular machinery responsible for protein degradation. This binding initiates the ubiquitination of BCR-ABL, marking it for destruction by the proteasome, the cell's protein degradation system.

12/1/2019

Hello, what is its activity as Potent and Selective BCR-ABL Degrader?

SIAIS178 exhibits potent activity against BCR-ABL with an IC50 of 24 nM. This low value indicates it only requires a small amount to significantly reduce BCR-ABL protein levels. It acts selectively towards BCR-ABL, meaning it primarily targets this protein and minimizes off-target effects on other proteins.

16/1/2019

Stock concentration: *

Desired final volume: *

Desired concentration: *

* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂