| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| Other Sizes |
| Targets |
IC50: 4.0 μM (UBA5), 78.5 μM (UAE), 66.8 μM (NAE)[1]
UBA5 (Ubiquitin-like modifier activating enzyme 5). UBA5-IN-1 is a selective inhibitor of UBA5 with an IC50 of 4.0 uM. It also inhibits UAE (IC50 = 78.5 uM) and NAE (IC50 = 66.8 uM), showing selectivity for UBA5. |
|---|---|
| ln Vitro |
UBA5-IN-1 (0.1-1000 μM) inhibits UAE and NAE with IC50 values of 78.5 and 66.8 μM, respectively, and exhibits a dose-dependent inhibition effect to UBA5 with an IC50 value of 4.0 μM[1]. In terms of ATP, UBA5 is non-competitively inhibited by UBA5-IN-1 (0–5 μM)[1]. The effects of UBA5-IN-1 (10 μM) on ATP binding to human kinase are negligible[1]. The proliferation of Sk-Luci6 cancer cells with high UBA5 expression levels is affected by UBA5-IN-1 (0–50 μM; 72 h)[1].
UBA5-IN-1 shows dose-dependent inhibition of UBA5 with an IC50 of 4.0 microM. It inhibits UAE and NAE with IC50 values of 78.5 microM and 66.8 microM, respectively, indicating selectivity for UBA5 over these related E1 enzymes. UBA5-IN-1 suppresses the proliferation of Sk-Luci6 cancer cells, which have high expression levels of UBA5, but further details on the specific proliferative effects are pending. |
| ln Vivo |
In vivo activity data for UBA5-IN-1 are not detailed in the available literature. As a selective inhibitor of UBA5, it has potential applications in studying the UBA5-UFM1 pathway in cancer and other diseases. Further in vivo studies would be required to characterize its efficacy, pharmacokinetics, and safety profile.
|
| Enzyme Assay |
For cell-free enzymatic assays, the activity of UBA5 is measured by the ATP-dependent formation of a UBA5-UFM1 thioester intermediate. UBA5-IN-1 is added to a reaction containing recombinant UBA5, UFM1, and ATP. The reaction is resolved by SDS-PAGE under non-reducing conditions, and the thioester intermediate is detected by Western blot with anti-UBA5 or anti-UFM1 antibodies. The compound's IC50 (4.0 uM) is calculated by quantitating the band intensity at increasing inhibitor concentrations.
|
| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: Sk-Luci6 cancer cells with high expression levels of UBA5 Tested Concentrations: 0-50 μM Incubation Duration: 0-72 h Experimental Results: demonstrated selective anti-proliferative activity for Sk-Luci6 cancer cells which expressed higher UBA5 protein levels, but demonstrated no anti-proliferative activity to MRC9 lung fibroblasts and A549 carcinoma cells. Cellular assays involve treating Sk-Luci6 cancer cells (which express high UBA5 levels) with UBA5-IN-1 at concentrations ranging from 1-50 uM for 24-72 hours. Cell viability and proliferation are assessed using MTT or CellTiter-Glo assays. The IC50 for growth inhibition would be determined. UFMylation levels in the cells are assessed by Western blot for UFM1-conjugated proteins to confirm on-target activity in a cellular context. |
| Animal Protocol |
For in vivo studies, UBA5-IN-1 could be formulated in a vehicle such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline and administered intraperitoneally or orally to mice bearing Sk-Luci6 or other UBA5-dependent xenografts. Doses would need to be optimized based on PK/PD modeling. Tumor volume and weight would be measured, and UFMylation levels in the tumor tissue would be assessed by Western blot.
|
| ADME/Pharmacokinetics |
UBA5-IN-1 has a molecular formula of C26H40F6N10O11S2Zn and a molecular weight of 912.16 g/mol. It is soluble in DMSO. The compound is typically stored as a powder at -20degC. Detailed pharmacokinetic parameters (half-life, bioavailability) are not publicly available. It is a small molecule, but its relatively high molecular weight may impact its physicochemical properties.
|
| Toxicity/Toxicokinetics |
Detailed toxicological data for UBA5-IN-1 are not available in the supplier literature. It is intended for research use only and not for human consumption. Standard laboratory safety precautions should be followed when handling this compound. Gloves, a lab coat, and eye protection should be worn. The compound should be used only in a well-ventilated area (e.g., a chemical fume hood).
|
| References | |
| Additional Infomation |
UBA5-IN-1 is a research-grade chemical, not an FDA-approved drug. It is one of the first small-molecule inhibitors of UBA5, an important enzyme in the UFMylation pathway, a post-translational modification system that is less studied than the ubiquitin and SUMO pathways but is involved in endoplasmic reticulum stress and protein homeostasis. It is a valuable chemical probe for target validation studies.
|
| Molecular Formula |
C26H40F6N10O11S2ZN
|
|---|---|
| Molecular Weight |
912.16
|
| Exact Mass |
910.151
|
| CAS # |
1831169-11-9
|
| PubChem CID |
102004328
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
7
|
| Hydrogen Bond Acceptor Count |
24
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
56
|
| Complexity |
914
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
C(F)(F)(F)S([O-])(=O)=O.C(N12CCN3CCN4CCN(CC1)[Zn+2]234)(=O)CCCCCNC([C@@H]1[C@H]([C@@H](O)[C@H](N2C=NC3=C(N=CN=C23)N)O1)O)=O
|
| InChi Key |
DLPRYIVGTKSVTR-WAYDLRBYSA-L
|
| InChi Code |
InChI=1S/C24H40N10O5.2CHF3O3S.Zn/c25-21-17-22(31-14-30-21)34(15-32-17)24-19(37)18(36)20(39-24)23(38)29-5-3-1-2-4-16(35)33-12-10-27-8-6-26-7-9-28-11-13-33;2*2-1(3,4)8(5,6)7;/h14-15,18-20,24,26-28,36-37H,1-13H2,(H,29,38)(H2,25,30,31);2*(H,5,6,7);/q;;;+2/p-2/t18-,19+,20-,24+;;;/m0.../s1
|
| Chemical Name |
zinc;(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxy-N-[6-oxo-6-(1,4,7,10-tetrazacyclododec-1-yl)hexyl]oxolane-2-carboxamide;trifluoromethanesulfonate
|
| 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 |
| 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) |
DMF: 100 mg/mL (109.63 mM)
DMSO: 50 mg/mL (54.81 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (1.37 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 12.5 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: ≥ 1.25 mg/mL (1.37 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 12.5 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: ≥ 1.25 mg/mL (1.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 1.25 mg/mL (1.37 mM) (saturation unknown) in 10% DMF 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: ≥ 1.25 mg/mL (1.37 mM) (saturation unknown) in 10% DMF 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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. Solubility in Formulation 6: ≥ 1.25 mg/mL (1.37 mM) (saturation unknown) in 10% DMF 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 | 1.0963 mL | 5.4815 mL | 10.9630 mL | |
| 5 mM | 0.2193 mL | 1.0963 mL | 2.1926 mL | |
| 10 mM | 0.1096 mL | 0.5481 mL | 1.0963 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
