2. PROTAC Metabolic Enzyme/Protease MAPK/ERK Pathway GPCR/G Protein
  3. Molecular Glues Oxidative Phosphorylation Ras
  4. JWJ-01-306

JWJ-01-306 is a CRBN-recruiting ZBTB11 Molecular Glues degrader. JWJ-01-306 degrades ZBTB11 and reprograms cellular metabolism, thereby reducing the level of Oxidative Phosphorylation and the activity of the tricarboxylic acid cycle. JWJ-01-306 enhances the response of organoids to K-Ras inhibition. JWJ-01-306 inhibits the proliferation of pancreatic ductal adenocarcinoma cells and melanoma cells. JWJ-01-306 can be used in studies related to pancreatic ductal adenocarcinoma and melanoma.

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JWJ-01-306

JWJ-01-306 Chemical Structure

CAS No. : 3069975-17-0

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JWJ-01-306 Related Antibodies

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Description

JWJ-01-306 is a CRBN-recruiting ZBTB11 Molecular Glues degrader. JWJ-01-306 degrades ZBTB11 and reprograms cellular metabolism, thereby reducing the level of Oxidative Phosphorylation and the activity of the tricarboxylic acid cycle. JWJ-01-306 enhances the response of organoids to K-Ras inhibition. JWJ-01-306 inhibits the proliferation of pancreatic ductal adenocarcinoma cells and melanoma cells. JWJ-01-306 can be used in studies related to pancreatic ductal adenocarcinoma and melanoma[1][2].
In Vitro

JWJ-01-306 (10 μM; 5 h) potently degrades endogenous ZBTB11 in MIA PaCa-2 cells via a CRBN- and proteasome-dependent mechanism. As measured by HiBiT quantification, the Dmax reaches 60%; whereas detected by immunoblotting, the Dmax reaches 90%[1].
JWJ-01-306 (10 μM; 1-14 days) acts synergistically with Sotorasib (HY-114277) to potently inhibit the proliferation of sotorasib-resistant MIA PaCa-2 cells, degrade ZBTB11, specifically impair cellular oxidative phosphorylation, reduce the basal oxygen consumption rate, maximal oxygen consumption rate and mitoATP/glycoATP ratio, downregulate ZBTB11-mediated transcription of mitochondrial ribosomal and complex I genes, disrupt tricarboxylic acid (TCA) cycle flux in cells, and induce reductive glutamine metabolism[1].
JWJ-01-306 (10 μM; 1-6 days) potently inhibits the proliferation of parental and MRTX1133 (HY-134813)-resistant SUIT2 cells, enhances the antiproliferative effect of MRTX1133 in drug-resistant cells, impairs cellular oxidative phosphorylation, and reduces the basal oxygen consumption rate, maximum oxygen consumption rate, and mitoATP/glycoATP ratio[1].
JWJ-01-306 (1 μM; 7 days) enhances the antiproliferative activity of MRTX1133 in pancreatic cancer organoids and deepens the response to K-Ras inhibition[1].
JWJ-01-306 (5 h) potently degrades endogenous ZBTB11 in MOLT-4 cells with a DC50 of 0.28 μM, reaching a maximum degradation rate of 72% after 5 h of treatment. It also degrades endogenous IKZF1 in Jurkat cells with a DC50 of 0.03 μM, achieving a maximum degradation rate of 85% after 5 h of treatment[2].
JWJ-01-306 (10 μM; 24 h) reduces oxidative phosphorylation (OxPhos) levels and mitochondrial ATP production in both parental and Dabrafenib (HY-14660)-resistant SK-MEL-5 melanoma cells[2].
JWJ-01-306 (10 μM; 14 days) reduces the proliferative capacity of both parental and Dabrafenib-resistant SK-MEL-5 melanoma cells[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

JWJ-01-306 Related Antibodies

Cell Proliferation Assay[1]

Cell Line: MIA PaCa-2 parental cells, MIA PaCa-2 sotorasib-resistant R2 cells
Concentration: 10 μM (single-agent JWJ-01-306); 10 μM JWJ-01-306 plus 1 μM sotorasib (combination treatment)
Incubation Time: 14 days
Result: Exerted only mild effects on proliferation over 14 days in parental MIA PaCa-2 cells.
Significantly impaired proliferation in combination with Sotorasib in Sotorasib-resistant MIA PaCa-2 R2 cells, while single-agent JWJ-01-306 had a moderate effect.

Cell Proliferation Assay[1]

Cell Line: SUIT2 parental cells, SUIT2 MRTX1133-resistant cells
Concentration: 10 μM (single-agent JWJ-01-306); 10 μM JWJ-01-306 plus 0.5 μM MRTX1133 (combination treatment)
Incubation Time: 6 days
Result: Completely impaired proliferation within 5 days in parental SUIT2 cells.
Blocked cell growth as a single agent and in combination with MRTX1133 in MRTX1133-resistant SUIT2 cells.

Real Time qPCR[1]

Cell Line: sotorasib-resistant MIA PaCa-2 cells, sotorasib-resistant MIA PaCa-2 cells stably expressing ZBTB11WT or ZBTB11K866T
Concentration: 10 μM
Incubation Time: 24 h
Result: Downregulated transcripts for 4 mitoribosome genes (MRPL48, MRPL44, MRPL1, MRPL30) and 4 complex I genes (NDUFS7, NDUFA12, NDUFC2, NDUFAF1).
Rescued JWJ-01-306-induced transcript downregulation for 7/8 downstream genes, and partially rescued MRPL1 transcript levels, when degradation-resistant ZBTB11K866T mutant was expressed.

Cell Proliferation Assay[2]

Cell Line: parental and Dabrafenib-resistant (DABR) SK-MEL-5 melanoma cells
Concentration: 10 μM
Incubation Time: 14 days
Result: Reduced proliferation of both parental and Dabrafenib-resistant SK-MEL-5 cell lines as a single agent.
Parmacokinetics
Species Dose Route T1/2 Cmax
Mice[1] 10 mg/kg i.p. 91 min 1.67 μM
Molecular Weight

574.98

Formula

C28H26ClF3N4O4
CAS No.
SMILES

FC(F)(F)C1=C(Cl)C=CC(CCNC2(CCC2)C3=CC(NC(C(N4C5CCC(NC5=O)=O)=O)=CC4=O)=CC=C3)=C1
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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JWJ-01-306 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

JWJ-01-3063069975-17-0Molecular GluesOxidative PhosphorylationRasZBTB11 Molecular Glues degraderpancreatic ductal adenocarcinoma and melanomaMIA PaCa-2 cellsUIT2 cellsMOLT-4 cellsSK-MEL-5 melanoma cellsInhibitorinhibitorinhibit

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