910297-51-7

Usage

Uses

Used in Oncology:
N-Deshydroxyethyl Dasatinib is used as an anticancer agent for the treatment of various types of cancers. It targets specific tyrosine kinases involved in cancer cell growth and proliferation, thereby inhibiting tumor progression.
Used in Immunology:
N-Deshydroxyethyl Dasatinib is also used in the treatment of immune diseases, as it can modulate the immune system's response and potentially alleviate autoimmune conditions.
Used in COVID-19 Research:
N-Deshydroxyethyl Dasatinib is a COVID-19-related research product, indicating its potential use in studying and treating the novel coronavirus disease. Its role in this context may involve targeting specific pathways or mechanisms related to the virus's impact on the human body.

InChI:InChI=1/C20H22ClN7OS/c1-12-4-3-5-14(21)18(12)27-19(29)15-11-23-20(30-15)26-16-10-17(25-13(2)24-16)28-8-6-22-7-9-28/h3-5,10-11,22H,6-9H2,1-2H3,(H,27,29)(H,23,24,25,26)

Upstream product

• 110-85-0 piperazine 
• 302964-08-5 2-(6-chloro-2-methylpyrimidin-4-ylamino)-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide 
• 302964-24-5 2-amino-N-(2-chloro-6-methylphenyl)-1.3-thiazole-5-carboxamide 
• 1780-26-3 2,4-dichloro-2-methylpyrimidine 
• 302964-06-3 [5-(2-chloro-6-methylphenylcarbamoyl)thiazol-2-yl]-carbamic acid tert-butyl ester 
• 87-63-8 2-chloro-6-methylaniline 
• 57260-71-6 1-t-Butoxycarbonylpiperazine 

Downstream Products

• 910297-62-0 ethyl 2-(4-(6-(5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-ylamino)-2-methylpyrimidin-4-yl)piperazin-1-yl)acetate 

Relevant academic research and scientific papers

Compound capable of degrading Bcr-Abl or PARP as well as preparation method and pharmaceutical application thereof

The invention relates to a compound shown in a general formula (Ia), (Ib), (Ic), (Id), (Ie), (If) or (Ig) or a stereoisomer, a deuterated compound, a solvate, a prodrug, a metabolite, a pharmaceutically acceptable salt or a co-crystal of the compound, an intermediate and a preparation method of the compound, and application of the compound in Bcr-Abl or PARP related diseases such as tumors. The chemical formula is B-K(Ia)B-Cy1-K(Ib)B-Cy1-Cy2-K(Ic)B-Cy1-Cy2-Cy3-K(Id)B-Cy1-Cy2-Cy3-Cy4-K(Ie).

Construction of an IMiD-based azide library as a kit for PROTAC research

As a promising protein degradation strategy, PROTAC technology is increasingly becoming a new star in cancer treatment. Here we report the efficient construction of an IMiD-based azide library via a quick one-step conversion of the existing IMiD-based ami

PROTEIN DEGRADATION TARGETING COMPOUND, ANTI-TUMOR APPLICATION, INTERMEDIATE THEREOF AND USE OF INTERMEDIATE

The present disclosure relates to compounds of formula (I) and their anti-tumor uses, and their intermediates of formula (III), intermediates of formula (IV), and uses of the intermediates. The compound of formula (I) has a degrading effect on a specific target protein, which is mainly composed of three parts. The first part is a small molecule compound (SMBP, Small Molecules Binding Protein) that can bind to a protein, the second part LIN is a linker, and the three-part ULM is a ubiquitin ligand (ULM, Ubiquitin Ligase Binding Moiety), wherein SMBP is covalently bound to LIN, and LIN is covalently bound to ULM. A series of compounds designed and synthesized in the present disclosure have a wide range of pharmacological activities, including the functions of degrading specific proteins and/or inhibiting activities of specific proteins, and thus can be used in related tumor treatments.

Discovery of novel BCR-ABL PROTACs based on the cereblon E3 ligase design, synthesis, and biological evaluation

Protein degradation is a promising strategy for drug development. Proteolysis-targeting chimeras (PROTACs) hijacking the E3 ligase cereblon (CRBN) exhibit enormous potential and universal degradation performance due to the small molecular weight of CRBN ligands. In this study, the CRBN-recruiting PROTACs were explored on the degradation of oncogenic fusion protein BCR-ABL, which drives the pathogenesis of chronic myeloid leukemia (CML). A series of novel PROTACs were synthesized by conjugating BCR-ABL inhibitor dasatinib to the CRBN ligand including pomalidomide and lenalidomide, and the extensive structure-activity relationship (SAR) studies were performed focusing on optimization of linker parameters. Therein, we uncovered that pomalidomide-based degrader 17 (SIAIS056), possessing sulfur-substituted carbon chain linker, exhibits the most potent degradative activity in vitro and favorable pharmacokinetics in vivo. Besides, degrader 17 also degrades a variety of clinically relevant resistance-conferring mutations of BCR-ABL. Furthermore, degrader 17 induces significant tumor regression against K562 xenograft tumors. Our study indicates that 17 as an efficacious BCR-ABL degrader warrants intensive investigation for the future treatment of BCR-ABL+ leukemia.

BIFUNCTIONAL DEGRADERS AND THEIR METHODS OF USE

Described herein are bifunctional degrader compounds, their various targets, their preparation, pharmaceutical compositions comprising them, and their use in the treatment of conditions, diseases, and disorders mediated by various target proteins.

N-phenyl-2-(pyrimidin-4-ylamino)thiazol-5-carboxamide derivatives, pharmaceutically acceptable salts thereof and a whitening material composition containing the same as an active ingredient

The present invention relates to a whitening material composition comprising an N-phenyl-2-(pyrimidin-4-ylamino)thiazole-5-carboxamide derivative as an active ingredient. Since the whitening material composition provided in one aspect of the present invention has an excellent effect of inhibiting the promotion of cell melanogenesis even when a small amount thereof is used, a cosmetic product for skin whitening and a product for preventing, alleviating, and treating melanin hyperpigmentation diseases can be usefully used.

Anti-tumor drug dasatinib-RGD conjugate, preparation method and application thereof

The invention is applicable to the technical field of medicine and provides an anti-tumor drug dasatinib-RGD conjugate, a preparation method and application thereof. The dasatinib-RGD conjugate provided by the invention is formed by connecting dasatinib and RGD through an amide bond. The preparation cost is low, the stability is good, the safety is good, and the conjugate meets the requirements ofclinical medication. The invention also provides nanomicelles composed of the anti-tumor drug dasatinib-RGD conjugate and a triblock polymer and anti-tumor application thereof. The dasatinib-RGD conjugate has high micellar drug loading, good stability and good biocompatibility, and in vivo tests show that the dasatinib-RGD conjugate can be efficiently accumulated in tumor tissues through active targeting and/or passive targeting, increases drug concentration in tumor tissues, has a good anti-tumor effect, realizes the effect-enhancing and toxicity-reducing purposes, and has a good market prospect and value.

COMPOUNDS TARGETING AND DEGRADING BCR-ABL PROTEIN AND ITS ANTITUMOR APPLICATION

The present disclosure provides a compound of formula (I) targeting and degrading BCR-ABL protein and its use in the field of antitumor. The compound of formula (I) shows degradation and inhibitory effects on BCR-ABL target protein, which is mainly comprised of four moieties, wherein the first moiety (BCR-ABL-TKIs) is compound moiety with BCR-ABL tyrosine kinase inhibited activity; the second moiety (the LIN) is link units; the third moiety (the ULM) is a small molecule ligand for VHL or CRBN proteases with ubiquitination; and the four moiety (the group A) is carbonyl group that covalently binds to BCR-ABL-TKIs and LIN, and the LIN is further covalently bonded to ULM. A series of compounds designed and synthesized by the present disclosure shows extensive pharmacological effective, which function to degrade BCR-ABL protein and inhibit BCR-ABL effective, and can be utilized for treating relevant tumor.

Azo-protac: Novel light-controlled small-molecule tool for protein knockdown

Reversibly altering endogenous protein levels are persistent issues. Herein, we designed photoswitchable azobenzene-proteolysis targeting chimeras (Azo-PROTACs) by including azobenzene moieties between ligands for the E3 ligase and the protein of interest

Global PROTAC Toolbox for Degrading BCR-ABL Overcomes Drug-Resistant Mutants and Adverse Effects

The BCR-ABL fusion oncoprotein causes chronic myeloid leukemia or acute lymphoblastic leukemia in Ph+ patients because the ABL kinase is constitutively activated. However, current clinical treatment with ABL inhibitors is seriously limited by drug resistance and adverse effects. Although the emerging proteolysis-Targeting chimeras (PROTACs) have been introduced to degrade BCR-ABL, most of them showed limited activity and could not overcome the common drug-resistant mutants, especially for T315I mutant. Herein, we systematically designed a set of unique PROTACs by globally targeting all the three binding sites of BCR-ABL, including dasatinib-, ponatinib-, and asciminib-based PROTACs. Our ponatinib-based PROTACs showed practical activity as dasatinib-based PROTACs, while no reported ponatinib-based PROTACs could degrade BCR-ABL before. As a proof of concept, some additional dasatinib-based PROTACs were then designed to degrade T315I mutant too. We provided a global PROTAC toolbox for degrading both wild-Type and T315I-mutated BCR-ABL from each binding site. More importantly, these PROTACs showed better selectivity and less adverse effects than the inhibitors, indicating that PROTACs had great potential for overcoming clinical drug resistance and safety issues.