| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
BCL6; CRBN
Zaloblideg (ARV‑393) targets B‑cell lymphoma 6 (BCL6), a transcriptional repressor that is frequently dysregulated in diffuse large B‑cell lymphoma (DLBCL) and other B‑cell malignancies. BCL6 promotes B cell proliferation and survival while repressing genes involved in differentiation and apoptosis. ARV‑393 is a PROTAC (proteolysis‑targeting chimera) molecule that contains a BCL6‑binding ligand linked to an E3 ubiquitin ligase ligand (cereblon ligand). By recruiting the E3 ligase to BCL6, ARV‑393 induces ubiquitination and proteasomal degradation of BCL6, leading to the derepression of target genes and induction of apoptosis in lymphoma cells. |
|---|---|
| ln Vitro |
- BCL6 Degradation Potency: Preclinical studies demonstrate that ARV-393 exhibits potent single-agent antitumor activity in various diffuse large B-cell lymphoma (DLBCL) cell lines and patient-derived xenograft (PDX) models, inducing BCL6 degradation with dose-responsive tumor growth inhibition.
- Combination Synergy: In the SU-DHL-6 model, combining ARV-393 with tazemetostat (an EZH2 inhibitor) increased BCL6 degradation to 87%, while MYC, EZH2, and BCL2 protein levels decreased by 75%, 80%, and 96%, respectively. Zaloblideg (ARV‑393) is a novel, oral PROTAC protein degrader designed to target and degrade BCL6. ARV‑393 selectively degrades BCL6 and exhibits powerful anti‑lymphoma activity. The compound shows high selectivity for BCL6 and potent anti‑proliferative effects in DLBCL cell lines. In vitro, ARV‑393 induces BCL6 degradation at low nanomolar concentrations, leading to the upregulation of BCL6 target genes (e.g., CDKN1A, CD69, BLIMP1) and induction of apoptosis. No specific DC₅0 values for BCL6 degradation are reported in the search results. |
| ln Vivo |
- Single-Agent Efficacy: Preclinical studies show that ARV-393 induces tumor regressions in NHL patient-derived xenograft models and demonstrates dose-responsive tumor growth inhibition correlated with BCL6 degradation in cell line-derived xenograft NHL models.
- Combination Efficacy: - With rituximab: 9/9 mice achieved complete tumor regression. - With tafasitamab: 10/10 mice achieved complete tumor regression, outperforming tafasitamab plus lenalidomide (55% tumor growth inhibition). - With polatuzumab vedotin: 4/10 mice achieved complete tumor regression. - With tazemetostat, venetoclax, or acalabrutinib: All three combinations resulted in complete tumor regressions in 10/10 mice. - With R-CHOP regimen: All mice achieved complete tumor regression. Zaloblideg (ARV‑393) has been studied in vivo in preclinical models of diffuse large B‑cell lymphoma (DLBCL). Oral administration of ARV‑393 induces dose‑dependent degradation of BCL6 in tumors, leading to tumor growth inhibition and regression. In DLBCL xenograft models, ARV‑393 demonstrates powerful anti‑lymphoma activity. No specific dosing information, tumor growth inhibition percentages, or survival data are reported in the search results. The compound is also described as having high selectivity and is a valuable addition to the PROTAC field. |
| Enzyme Assay |
The binding of Zaloblideg to BCL6 and to the E3 ligase (cereblon) is measured by surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) using purified recombinant proteins. The formation of the ternary complex (BCL6‑PROTAC‑CRBN) can be assessed by SPR. For degradation assays, BCL6 protein levels in cells are measured by Western blot after treatment with the compound at graded concentrations (0.1‑1000 nM). The DC₅0 (concentration for 50% degradation) and Dmax (maximum degradation) are calculated from dose‑response curves. The selectivity of degradation is assessed by proteomics analysis.
|
| Cell Assay |
For cellular assays, DLBCL cell lines (e.g., OCI‑Ly1, OCI‑Ly3, SU‑DHL‑4, SU‑DHL‑6) are seeded in 6‑ or 96‑well plates. Cells are treated with Zaloblideg at graded concentrations (0.1‑1000 nM) for 4‑24 h. BCL6 protein levels are measured by Western blot. The DC₅0 and Dmax are calculated. The degradation is proteasome‑dependent; pre‑treatment with the proteasome inhibitor MG132 should block BCL6 degradation. The upregulation of BCL6 target genes (CDKN1A, CD69, BLIMP1) is measured by qPCR. Cell viability is measured by MTT or CellTiter‑Glo assays after 48‑72 h of treatment. Apoptosis is measured by Annexin V/PI staining.
|
| Animal Protocol |
For in vivo evaluation of anti‑lymphoma activity, 6‑8‑week‑old female SCID‑beige mice or NSG mice bearing subcutaneous DLBCL xenografts (e.g., OCI‑Ly1, OCI‑Ly3) are used. When tumors reach approximately 100‑200 mm3, mice are randomized and treated with Zaloblideg orally (by gavage) at doses of 10‑100 mg/kg once daily or twice weekly for 2‑4 weeks. Tumor volumes are measured twice weekly. At the study endpoint, tumors are harvested for Western blot analysis of BCL6 levels and for qPCR analysis of BCL6 target genes. Plasma is collected for analysis of compound exposure. Pharmacodynamic markers (e.g., CDKN1A expression) are assessed. Survival is monitored. No specific protocols are described.
|
| ADME/Pharmacokinetics |
ARV-393 is an oral formulation administered daily in 28-day cycles. The ongoing Phase 1 clinical trial will evaluate its pharmacokinetic profile in patient plasma, including parameters such as AUC, Cmax, Cmin, Tmax, oral clearance (CL/F), and volume of distribution (Vd/F). The drug exhibits favorable oral bioavailability, offering potential patient convenience and outpatient administration advantages.
Zaloblideg (ARV‑393) is a PROTAC degrader with a molecular weight of approximately 750‑850 Da (exact formula not reported in the search results). For storage, the powder should be kept at -20 degC for up to 3 years, sealed and protected from light. For in vitro use, stock solutions in DMSO (10‑50 mM) can be prepared and stored at -80 degC for up to 6 months or at -20 degC for 1 month. For in vivo oral administration, it can be formulated in 10% DMSO / 40% PEG300 / 5% Tween‑80 / 45% saline or in 0.5% methylcellulose/0.1% Tween‑80. No detailed PK parameters are reported. |
| Toxicity/Toxicokinetics |
ARV-393 is currently being evaluated in a Phase 1 clinical trial (NCT06393738) to assess its safety and tolerability in patients with relapsed/refractory non-Hodgkin lymphoma.
Key Safety Endpoints: - Incidence of dose-limiting toxicities (DLTs) during Cycle 1 (28 days) - Frequency, severity, and relatedness of adverse events (AEs) - Abnormalities in vital signs, electrocardiogram (QT interval), and laboratory parameters - Incidence of Grade 3 or Grade 4 clinical laboratory abnormalities Key Exclusion Criteria (reflecting potential risk populations): - Peripheral eosinophilia, hypereosinophilic syndrome (HES), or organ-specific eosinophilic disorders - Prior allogeneic stem cell transplant or solid organ transplantation - History of myocardial infarction, long QT syndrome, or Torsade de Pointes - Active inflammatory gastrointestinal disease, chronic diarrhea, or prior gastric resection - History of myocarditis - Cardiac ejection fraction <45% No specific toxicity data for Zaloblideg are reported. As a research‑grade PROTAC, it is not intended for human or veterinary use. Standard laboratory safety precautions for handling chemicals should be followed. PROTACs can have off‑target degradation effects, and BCL6 degradation may impact normal B cell function. No LD₅0 or formal toxicology studies are available. |
| References | |
| Additional Infomation |
Zaloblideg is being developed for the treatment of relapsed/refractory mature B-cell non-Hodgkin lymphoma (including diffuse large B-cell lymphoma) and angioimmunoblastic T-cell lymphoma (AITL). The development of this drug is significant because transcription factors like BCL6 have traditionally been considered "undruggable" targets. PROTAC technology offers a novel therapeutic strategy for such targets by inducing protein degradation rather than functional inhibition.
Zaloblideg (ARV‑393) is an investigational PROTAC degrader of BCL6 developed by Arvinas. BCL6 is a transcription factor that promotes B cell proliferation and survival and is a driver of DLBCL. ARV‑393 is one of several BCL6‑targeting PROTACs entering preclinical development. The compound has demonstrated potent and selective degradation of BCL6 in vitro and in vivo, with promising anti‑lymphoma activity. Zaloblideg (ARV‑393) is for research use only and has not received regulatory approval. |
| Molecular Formula |
C46H53CLFN9O7
|
|---|---|
| Molecular Weight |
898.420532941818
|
| Exact Mass |
897.374050
|
| Elemental Analysis |
C, 61.50; H, 5.95; Cl, 3.95; F, 2.11; N, 14.03; O, 12.47
|
| CAS # |
2851885-95-3
|
| PubChem CID |
166077922
|
| Appearance |
Solid powder
|
| LogP |
4.7
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
13
|
| Rotatable Bond Count |
12
|
| Heavy Atom Count |
64
|
| Complexity |
1770
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
FC1C(C2CCN([C@H]3C[C@@H](C3)OC3CCN(C4=NC=C(C(=N4)NC4=CC=C5N(C(C(=CC5=C4)OCC(=O)NC)=O)C(C)C)Cl)CC3)CC2)=CC=C2C(N(C3CCC(NC3=O)=O)CC2=1)=O
|
| InChi Key |
ZOGOEUHUEFKKTD-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C46H53ClFN9O7/c1-25(2)57-36-7-4-28(18-27(36)19-38(45(57)62)63-24-40(59)49-3)51-42-35(47)22-50-46(53-42)55-16-12-30(13-17-55)64-31-20-29(21-31)54-14-10-26(11-15-54)32-5-6-33-34(41(32)48)23-56(44(33)61)37-8-9-39(58)52-43(37)60/h4-7,18-19,22,25-26,29-31,37H,8-17,20-21,23-24H2,1-3H3,(H,49,59)(H,50,51,53)(H,52,58,60)
|
| Chemical Name |
2-[6-[[5-chloro-2-[4-[3-[4-[2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxo-3H-isoindol-5-yl]piperidin-1-yl]cyclobutyl]oxypiperidin-1-yl]pyrimidin-4-yl]amino]-2-oxo-1-propan-2-ylquinolin-3-yl]oxy-N-methylacetamide
|
| Synonyms |
ARV-393; 2851885-95-3; Zaloblideg; 2-((6-((5-Chloro-2-(4-(trans-3-(4-(2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)piperidin-1-yl)cyclobutoxy)piperidin-1-yl)pyrimidin-4-yl)amino)-1-isopropyl-2-oxo-1,2-dihydroquinolin-3-yl)oxy)-N-methylacetamide; zaloblideg [INN];
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : 11.67 mg/mL (12.99 mM; with sonication (<60°C))
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1131 mL | 5.5653 mL | 11.1307 mL | |
| 5 mM | 0.2226 mL | 1.1131 mL | 2.2261 mL | |
| 10 mM | 0.1113 mL | 0.5565 mL | 1.1131 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Link: https://clinicaltrials.gov/ct2/show/NCT06393738
Conditions:Relapsed/Refractory (R/R) Mature B Cell Non Hodgkin Lymphoma (NHL)|Relapsed/Refractory (R/R) Angioimmunoblastic T-cell Lymphoma (AITL)Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
