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| 10mg |
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| Targets |
VPC-80051 targets the RNA-binding domain (RBD) of hnRNP A1, a splicing factor involved in alternative splicing regulation. By inhibiting hnRNP A1 splicing activity, it reduces AR-V7 messenger RNA levels in 22Rv1 CRPC cells. AR-V7 is a constitutively active androgen receptor splice variant associated with castration-resistant prostate cancer (CRPC) and resistance to anti-androgen therapies. The compound directly interacts with the RNA-binding domain of hnRNP A1.
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| ln Vitro |
In the 22Rv1 CRPC cell line, VPC-80051 directly interacts with the hnRNP A1 RBD to lower the levels of AR-V7 messenger. Multifunctional RNA-binding protein hnRNP A1 controls translation of cellular transcripts in both healthy and pathological settings, as well as alternative pre-mRNA splicing, transcription, nucleocytoplasmic shuttling, miRNA processing, and telomere elongation maintenance[1].
VPC-80051 directly interacts with the hnRNP A1 RBD and reduces AR-V7 messenger levels in the 22Rv1 CRPC cell line. This demonstrates its ability to modulate alternative splicing of the androgen receptor pre-mRNA, reducing the production of the constitutively active AR-V7 splice variant. The compound is a prototype inhibitor of the hnRNP A1 splicing factor. Further experimental evaluation demonstrated that VPC-80051 interacts directly with hnRNP A1 RBD and reduces AR-V7 messenger levels in 22Rv1 CRPC cell line. |
| ln Vivo |
In vivo activity has not been extensively reported for VPC-80051 racemate. As a research tool compound targeting hnRNP A1 splicing, its in vivo efficacy and pharmacokinetic properties require further investigation. The compound is primarily characterized through in vitro studies. The compound is used for prostate cancer research.
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| Enzyme Assay |
The binding of VPC-80051 to the hnRNP A1 RBD can be assessed using biophysical techniques such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) to measure direct protein-ligand interactions. Competitive binding assays may also be employed to evaluate the compound's affinity for the RNA-binding domain. The compound was discovered using a computer-aided drug discovery approach.
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| Cell Assay |
In vitro studies are performed in 22Rv1 CRPC cells treated with VPC-80051. AR-V7 and full-length androgen receptor (AR-FL) mRNA levels are quantified by RT-qPCR to assess the compound's effect on hnRNP A1-mediated splicing. The reduction in AR-V7 messenger levels indicates successful inhibition of hnRNP A1 splicing activity. The compound directly interacts with the RNA-binding domain of hnRNP A1.
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| Animal Protocol |
In vivo studies for VPC-80051 would typically involve xenograft mouse models of castration-resistant prostate cancer to evaluate tumor growth inhibition and AR-V7 suppression. However, specific in vivo protocols for this compound have not been reported in the available literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for VPC-80051 racemate have not been reported. As a small molecule inhibitor, its properties would depend on factors such as solubility, metabolic stability, and protein binding. Further optimization may be needed for in vivo applications. The compound is soluble in DMSO at 55 mg/mL and in vivo formulation is possible using 10% DMSO+40% PEG300+5% Tween 80+45% Saline.
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| Toxicity/Toxicokinetics |
No toxicity data are available for VPC-80051 racemate. As a research compound, it should be handled with standard laboratory safety precautions. Its safety profile has not been systematically evaluated. The compound is for research use only.
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| References |
[1]. Carabet LA, et al. Computer-Aided Discovery of Small Molecules Targeting the RNA Splicing Activity of hnRNP A1 in Castration-Resistant Prostate Cancer. Molecules. 2019;24(4):763. Published 2019 Feb 20.
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| Additional Infomation |
VPC-80051 racemate is a research compound not approved for clinical use. It represents a pioneering approach to targeting RNA splicing factors in cancer therapy, specifically for castration-resistant prostate cancer where AR-V7 drives resistance. The compound serves as a valuable tool for studying hnRNP A1 function and alternative splicing in cancer biology. It was discovered by using a computer-aided drug discovery approach. The compound is the first small molecule inhibitor of hnRNP A1 splicing activity discovered to date.
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| Molecular Formula |
C16H13F2N3O
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|---|---|
| Molecular Weight |
301.290730237961
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| Exact Mass |
301.102
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| CAS # |
877969-69-2
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| PubChem CID |
8258823
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| Appearance |
White to off-white solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
22
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| Complexity |
409
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@@H](C1=CC(=C(C=C1)F)F)NC(=O)C2=NNC3=CC=CC=C32
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| InChi Key |
MVHNHGGJTMFAQP-VIFPVBQESA-N
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| InChi Code |
InChI=1S/C16H13F2N3O/c1-9(10-6-7-12(17)13(18)8-10)19-16(22)15-11-4-2-3-5-14(11)20-21-15/h2-9H,1H3,(H,19,22)(H,20,21)/t9-/m0/s1
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| Chemical Name |
N-[(1S)-1-(3,4-difluorophenyl)ethyl]-1H-indazole-3-carboxamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (331.91 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.30 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 25.0 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: 2.5 mg/mL (8.30 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (8.30 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 | 3.3191 mL | 16.5953 mL | 33.1906 mL | |
| 5 mM | 0.6638 mL | 3.3191 mL | 6.6381 mL | |
| 10 mM | 0.3319 mL | 1.6595 mL | 3.3191 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.
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