| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
| Targets |
AU-15330 targets the SWI/SNF ATPase components SMARCA2 and SMARCA4, as well as PBRM1, for proteasomal degradation through the VHL E3 ubiquitin ligase pathway. The SWI/SNF complex is a chromatin remodeler critical for gene expression regulation, and its ATPase subunits are oncogenic drivers in various cancers. By degrading these subunits, AU-15330 disrupts SWI/SNF complex function and chromatin accessibility. It shows preferential cytotoxicity in enhancer-binding transcription factor-addicted cancers at low nanomolar concentrations.
|
|---|---|
| ln Vitro |
In vitro, AU-15330 exhibits cytotoxicity in H3.3K27M cells but not in H3 wild-type cells, demonstrating selective activity against cells harboring this oncogenic histone mutation. Western blot analysis shows rapid and near-complete loss of SMARCA2, SMARCA4, and PBRM1 proteins in cancer cells treated with AU-15330 at concentrations as low as 100 nM to 1 µM. The compound disrupts chromatin accessibility at over 30,000 sites in VCaP cells with as little as 1 hour of treatment.
|
| ln Vivo |
AU-15330 (10 and 30 mg/kg; intravenously; 5 days per week for 3 weeks) showed no significant toxicity in immunocompetent mice [1]. AU-15330 (60 mg/kg with or without enzalutamide 10 mg/kg; intravenously; 3 days per week; access; 5 days per week for 5 weeks) effectively inhibits tumor growth by more than 20% Causes disease regression in animals. The combination regimen induced the most potent AU-15330 (60 mg/kg with or without 10 mg/kg enzalutamide; iv; 3 days per week; side; 5 days per week for 5 weeks) as a single agent and It interacts well with enzalutamide and strongly inhibits the growth of C4-2B cell line-derived CRPC xenografts in intact mice [1]. AU-15330 (60 mg/kg with or without 10 mg/kg enzalutamide; iv; 3 days per week; sidewall 5 days per week for 5 weeks) significantly inhibits Tumor growth, resulting in tumor regression in more than 30% of animals, was induced in the CRPC variant model of MDA-PCa-146-12 PDX via a tumor-suffocating nozzle [1].
In vivo, AU-15330 induces potent tumor growth inhibition in xenograft models of prostate cancer. It acts synergistically with the androgen receptor (AR) antagonist enzalutamide, enhancing therapeutic efficacy. In mouse models, AU-15330 is well tolerated and induces on-target degradation of SMARCA2, SMARCA4, and PBRM1. Non-tumor bearing CD-1 mice treated with AU-15330 show degradation of target proteins in various tissues. |
| Enzyme Assay |
For in vitro degradation assays, cells are treated with AU-15330 at concentrations ranging from 0.01-10 µM for 4-24 hours. Cell lysates are prepared and subjected to SDS-PAGE followed by Western blotting with antibodies against SMARCA2, SMARCA4, PBRM1, and vinculin as loading control. Protein band intensities are quantified by densitometry and normalized to loading controls to determine degradation efficiency. Time-course experiments can assess the kinetics of target protein degradation.
|
| Cell Assay |
For cell viability assays, cancer cell lines are seeded in 96-well plates and treated with AU-15330 at various concentrations (0.001-10 µM) for 72-96 hours. Cell viability is measured using CellTiter-Glo or MTT assays. IC50 values are calculated from dose-response curves. Cytotoxicity is compared between H3.3K27M mutant cells and H3 wild-type cells to assess selective activity. Colony formation assays can also be performed to evaluate long-term anti-proliferative effects.
|
| Animal Protocol |
Animal/Disease Models: VCaP castration-resistant tumor model (sixweeks old male CB17 severe combined immunodeficiency (SCID) mice) [1]
Doses: 60 mg/kg with or without 10 mg/kg enzalutamide Route of Administration: intravenous (iv) (iv)injection (3 days per week)); po (5 days per week for 5 weeks) Experimental Results: Inhibited tumor growth and induced disease regression in more than 20% of animals. Combination therapy induced the most potent antitumor effect and regression occurred in all animals. Animal/Disease Models: C4-2B non-castrated tumor model (sixweeks old male CB17 severe combined immunodeficiency (SCID) mice) [1] Doses: 60 mg/kg with or without 30 mg/kg enzalutamide Doses: IV (3 days per week); PO (5 days per week for 4 weeks) Experimental Results: As a single agent and synergistically with enzalutamide, strong inhibition of C4-2B cell line in intact mice Growth of derived CRPC xenografts. For in vivo efficacy studies, immunodeficient mice are subcutaneously implanted with prostate cancer cells (such as VCaP or LNCaP). When tumors reach approximately 100-200 mm³, mice are randomized and treated with AU-15330 at doses determined from pharmacokinetic studies. Tumor volumes are measured twice weekly with calipers. At study endpoint, tumors are collected for Western blot analysis to confirm target degradation and for histopathological examination. Combination studies with enzalutamide can be performed to evaluate synergistic effects. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of AU-15330 have been evaluated in preclinical studies. The compound is soluble in DMSO and ethanol at 100 mg/mL but is insoluble in water. For in vivo administration, it can be formulated as a homogeneous suspension in CMC-Na (≥5 mg/mL) or as a clear solution in 5% DMSO + 40% PEG300 + 5% Tween 80 + 50% ddH2O. The compound is well tolerated in mice at efficacious doses. Further PK parameters would be detailed in the primary literature.
|
| Toxicity/Toxicokinetics |
In preclinical studies, AU-15330 is well tolerated in mice at doses that induce on-target degradation. The compound shows no significant toxicity at efficacious doses in xenograft models. Comprehensive toxicology studies have not been reported in the available literature. As a research compound, AU-15330 is not intended for human use and should be handled with appropriate safety precautions in laboratory settings.
|
| References | |
| Additional Infomation |
AU-15330 is a VHL-dependent PROTAC degrader that simultaneously targets SMARCA2, SMARCA4, and PBRM1 for degradation. It exhibits cytotoxicity in H3.3K27M cells but not in H3 wild-type cells. AU-15330 induces potent tumor growth inhibition in prostate cancer xenograft models and acts synergistically with enzalutamide. It disrupts chromatin accessibility at thousands of genomic sites. The compound is a research tool and is not approved for clinical use.
|
| Molecular Formula |
C39H49N9O5S
|
|---|---|
| Molecular Weight |
755.93
|
| Exact Mass |
755.357
|
| CAS # |
2380274-50-8
|
| Related CAS # |
AU-16235;2380275-40-9
|
| PubChem CID |
156168451
|
| Appearance |
Off-white to yellow solid powder
|
| LogP |
3.3
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
12
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
54
|
| Complexity |
1280
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
C(N1C[C@H](O)C[C@H]1C(=O)N[C@H](C1C=CC(C2SC=NC=2C)=CC=1)C)(=O)[C@H](C(C)(C)C)NC(=O)CN1CCN(C2=C(N=NC(C3C=CC=CC=3O)=C2)N)CC1
|
| InChi Key |
HDCCMCFIGHIDJR-TUDDPRDOSA-N
|
| InChi Code |
InChI=1S/C39H49N9O5S/c1-23(25-10-12-26(13-11-25)34-24(2)41-22-54-34)42-37(52)31-18-27(49)20-48(31)38(53)35(39(3,4)5)43-33(51)21-46-14-16-47(17-15-46)30-19-29(44-45-36(30)40)28-8-6-7-9-32(28)50/h6-13,19,22-23,27,31,35,49-50H,14-18,20-21H2,1-5H3,(H2,40,45)(H,42,52)(H,43,51)/t23-,27+,31-,35+/m0/s1
|
| Chemical Name |
(2S,4R)-1-[(2S)-2-[[2-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide
|
| 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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ~140 mg/mL (~185.20 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.5 mg/mL (4.63 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3.5 mg/mL (4.63 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 3.5 mg/mL (4.63 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3229 mL | 6.6144 mL | 13.2287 mL | |
| 5 mM | 0.2646 mL | 1.3229 mL | 2.6457 mL | |
| 10 mM | 0.1323 mL | 0.6614 mL | 1.3229 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
