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PROTACPROTAC Selection
Selection of target proteins for PROTAC can be based on the following considerations: 1. Whether the protein is specific or not, non-specific proteins can cause off-target toxicity; 2. Whether the protein belongs to the molecules that can be degraded by PROTAC, and it has been reported that the targets that can be used for PROTAC include, kinases (MEK, KRAS, CDK, and Bcr/Abl), transcription factors (e.g. p53, STAT, RAR, ER, and AR), epigenetic factors (e.g., HDAC and BET bromodomain), and E3 ligases themselves (e.g., MDM2), among others; 3. Whether or not the protein has been reported to have a ligand or crystalline form that can be commercially engineered.
ARV-825
T54341818885-28-7
ARV-825, a heterobifunctional PROTAC (Proteolysis Targeting Chimera) that recruits BRD4 to the E3 ubiquitin ligase cereblon leading to fast, efficient, and prolonged degradation of BRD4 in all BL cell lines tested.
- $60
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AK-1690
T2010322984505-88-4
AK-1690 is a potent and selective STAT6 PROTAC degrader that induces degradation of STAT6 proteins in cells (DC50=1 nM) and depletes STAT6 proteins in mouse tissues, which can be used in cancer research.
- $510
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Nrf2 degrader 30
T2013953025286-29-4
Nrf2 degrader 30 is a small molecule PROTAC that inhibits the degradation of Nrf2, thereby enhancing its activity. Nrf2 is a key transcription factor that regulates cellular antioxidant responses and various protective mechanisms. The activity of Nrf2 is primarily regulated by its interaction with Keap1, which serves as an E3 ubiquitin ligase complex adapter to promote Nrf2 ubiquitination and proteasomal degradation。
- $795
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Fmoc-PEA
T17977329223-23-6In house
Fmoc-PEA (Example 1-2) is utilized as a cleavable linker for antibody-drug conjugates (ADC).
- $38
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dBET6
T51301950634-92-0
dBET6 is a selective and cell-permeable degrader of BET based on PROTAC (IC50: 14 nM). It has antitumor activity.
- $48
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cis VH 032, amine dihydrochloride
T354782376990-32-6
cis VH 032, amine dihydrochloride ((S,S,S)-AHPC) is a negative control for the functionalized VHL ligand VH 032, amine .
- $31
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A947
T746862378056-80-3
A947 is a potent and selective SMARCA2 protein hydrolysis-targeted chimeric molecule (PROTAC) that induces the degradation of SMARCA2 by binding to VHL E3 ubiquitin ligase, with significant antitumor activity in vivo and in vitro, especially in SMARCA4-mutant non-small cell lung cancer (NSCLC) cells.
- $1,070
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MT-802
T161572231744-29-7
MT-802 is an effective BTK degrader based on PROTAC technology (DC50: 1 nM). MT-802 has the potential to treat C481S mutant chronic lymphocytic leukemia (CLL).
- $88
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Dbet57
T54401883863-52-2
dBET57 is heterobifunctional degrader of BRD4 based on the PROTAC technology, exhibits significant degradation of BRD4BD1 with a DC50 5h of 500 nM ,and inactive on BRD4BD2
- $42
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ARV-771
T54351949837-12-0
ARV-771 is an effective BET degrader based on PROTAC technology. The Kd for BRD2(1), BRD2(2), BRD3(1), BRD3(2), BRD4(1) and BRD4(2) are 34 and 4.7 respectively. , 8.3, 7.6, 9.6 and 7.6 nM.
- $55
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ACBI1
T173502375564-55-7
ACBI1 is a potent PROTAC degrader of BAF ATPase subunits SMARCA2 and SMARCA4, also degrades the polybromo-associated BAF (PBAF) complex member PBRM1, with DC50s of 6 nM, 11 nM and 32 nM for SMARCA2, SMARCA4 and PBRM1 in MV-4-11 cells, respectively. ACBI1 is composed of a bromodomain ligand, a linker, and the E3 ubiquitin ligase VHL. ACBI1 can induce anti-proliferative effects and apoptosis.
- $98
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DT2216
T136652365172-42-3
DT2216 inhibits various Bcl-XL-dependent leukemias and cancer cells, but is significantly less toxic to platelets.DT2216 is a selective B-cell lymphoma, extremely large (BCL-XL), proteolytic targeting chimera (PROTAC).DT2216 targets bcl-XL to the Von Hipp
- $71
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JQAD1
T411802417097-18-6
JQAD1 is a potent and selective histone acetyltransferase EP300 degrader (PROTAC®; DC50≤ 31.6 nM); comprises an EP300 inhibitor, A485, joined by a linker to a cereblon E3 ligase ligand. JQAD1 brings about degradation of EP300 in neuroblastoma cell lines in a proteasome-dependent manner. JQAD1 suppresses both H3K27ac and EP300 expression levels and induces apoptosis. JQAD1 suppresses tumors growth in NSG mice xenografted with Kelly cells. CRC and MYCN genes are downregulated in tumors treated with JQAD1. JQAD1 exhibits no significant effect on coactivator CBP at concentrations inducing EP300 degradation.
- $131
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BSJ-03-123
T53952361493-16-3
BSJ-03-123 is a potent, CDK6-selective small-molecule degrader.
- $84
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PROTAC IRAK4 degrader-1
T138422360533-90-8
PROTAC IRAK4 degrader-1 (compound I-210) is a Cereblon based PROTAC consisting of the PROTAC IRAK4 ligand-1, the E3 ligase ligand Pomalidomide and the PROTAC linker AM-Imidazole-PA-Boc.
- $471
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BETd-260
T145502093388-62-4In house
BETd-260, a PROTAC linked by a Cereblon ligand and a BET ligand, has an inhibitory effect on BRD4 protein in leukemic cell lines.
- $132
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PROTAC CDK9 degrader 4
T399962411021-01-5
PROTAC CDK9 degrader 4 is a highly potent CDK9 degrader that targets transcriptional regulation and has potential anticancer activity for the study of acute myelogenous leukemia (AML).
- $322
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MD-224
T119802136247-12-4
MD-224 is a highly potent and efficacious MDM2 degrader based on the proteolysistargeting chimera (PROTAC) concept,and as a new class of anticancer agent.
- $64
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dBRD9 HCl
T31221L2341840-98-8
dBRD9 HCl is a PROTAC composed of the BRD9 inhibitor BI 7273 conjugated to the cereblon E3 ligase ligand pomalidomide . dBRD9 HCl is a potent and selective degrader of BRD9 (IC50 = 56.6 nM in MOLM-13 cells). dBRD9 HCl does not degrade BRD4 or BRD7 at concentrations up to 5 μM. dBRD9 HCl displays antiproliferative effects in human AML cell lines.
- $197
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VH032
T291061448188-62-2In house
VH032 commonly used as a precursor to a PROTAC that hijacks VHL as the E3 ubiquitin ligase component.VH032 is a VHL HIF-1α interaction inhibitor with a KdPROTACs, which can recruit von Hippel-Lindau (VHL) proteins as a ligand of VHL.
- $44
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β-NF-JQ1
T105262380000-55-3In house
β-NF-JQ1 is a PROTAC that recruits aryl hydrocarbon receptor E3 (AhR E3) ligase to target proteins. Using β-NF as an AhR ligand, it targets bromodomain (BRD)-containing proteins and induces AhR and BRD protein interactions. β-NF-JQ1 exhibits potent anticancer activity associated with protein knockdown activity.
- $44
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MS4078
T161532229036-62-6
MS4078 is an inhibitor and aplastic lymphoma kinase (ALK) PROTAC (degrader) based on Cereblon ligand, with a Kd of 19 nM for binding affinity to ALK.
- $44
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GSK215
T678432743427-26-9
GSK215 is a potent and selective PROTAC focal adhesion kinase (FAK) degrader (pDC50= 8.4), designed using the FAK inhibitor VS-4718 and a binder for the VHL E3 ligase, capable of inducing rapid and prolonged FAK degradation.
- $127
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