| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
UBX1325 specifically targets the B-cell lymphoma-extra large (BCL-xL) protein, a member of the Bcl-2 family of apoptosis regulators. As a BCL-xL inhibitor, it binds to and neutralizes this anti-apoptotic protein, thereby facilitating the programmed cell death of senescent cells that accumulate in retinal tissues. These senescent cells contribute to chronic inflammation, angiogenesis, and photoreceptor dysfunction through senescence-associated secretory phenotypes (SASPs), making BCL-xL inhibition a promising therapeutic strategy.
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| ln Vitro |
Intravitreal (IVT) injection of UBX1325 reduced anti-apoptotic Bcl-xL:Bim complexes in the retina of C57BL/6 mice model of oxygen-induced retinopathy (OIR) [1]. In mice with streptozotocin (STZ)-induced retinopathy, UBX1325 can lower retinal vascular permeability and enhance retinal neovascularization [1].
In vitro, UBX1325 exhibits potent anti-senescent activity by selectively inducing apoptosis in senescent cells while sparing non-senescent cells. As a Bcl-xL inhibitor, it effectively promotes the elimination of aged and dysfunctional cells that accumulate with age or in disease states. This mechanism has been confirmed in cellular models of senescence, where treatment leads to increased caspase activation and decreased viability specifically in the senescent cell population. These activities support its classification as an effective anti-aging agent. |
| ln Vivo |
In vivo, UBX1325 has demonstrated efficacy in animal models of age-related ocular diseases, including diabetic macular edema (DME), age-related macular degeneration (AMD), and diabetic retinopathy (DR). By eliminating senescent cells from retinal tissues, the compound reduces chronic inflammation and abnormal angiogenesis, leading to improved visual function. Preclinical studies show that UBX1325 promotes photoreceptor survival and preserves retinal architecture, providing a foundation for its advancement into clinical trials for these debilitating eye diseases.
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| Enzyme Assay |
For non-cell-based receptor binding assays, the affinity of UBX1325 for BCL-xL can be measured using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). Recombinant BCL-xL protein is immobilized on a sensor chip or in a sample cell. UBX1325 is flowed over the chip at varying concentrations (0.1-10,000 nM) in PBS buffer containing 0.05% Tween-20 and 1% DMSO. The binding affinity (KD), association rate (kon), and dissociation rate (koff) are determined. Alternatively, a fluorescence polarization competition assay using a fluorescently labeled BH3 peptide can be performed.
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| Cell Assay |
For in vitro cell-based assays, human retinal pigment epithelial (RPE) cells or primary fibroblasts are induced into senescence using ionizing radiation (10 Gy) or replicative exhaustion. Cells are seeded in 96-well plates at 5 × 10^3 cells/well. After 24 hours, cells are treated with varying concentrations of UBX1325 (0.1-10,000 nM) for 48-72 hours. Cell viability is assessed using the CellTiter-Glo luminescent assay or by Annexin V-FITC/PI staining followed by flow cytometry. Senescence-associated beta-galactosidase (SA-beta-gal) staining is used to confirm selective elimination of senescent cells.
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| Animal Protocol |
For in vivo animal studies, an age-related macular degeneration (AMD) mouse model can be used. Female C57BL/6 mice (6-8 weeks old) undergo laser-induced choroidal neovascularization (CNV) to mimic wet AMD. UBX1325 is administered via intravitreal injection at doses of 0.1-1 mg/eye on day 0 and day 7. Control animals receive vehicle (PBS). At day 14, mice are euthanized, and eyes are enucleated for histological analysis. CNV area is measured in choroidal flat mounts stained with isolectin B4. Retinal sections are analyzed for photoreceptor integrity and microglial activation. Senescent cell markers (p16INK4a, p21) are quantified by immunohistochemistry.
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| ADME/Pharmacokinetics |
UBX1325 (Foselutoclax) has a molecular weight of 1159.7 g/mol and is administered intravitreally for ocular indications. The compound is a phosphate pro-drug that is converted to the active metabolite following administration. Pharmacokinetic studies in animal models show that intravitreal injection provides sustained drug exposure in the retina and vitreous humor, with minimal systemic absorption. The elimination half-life from the vitreous is approximately 7-10 days, supporting monthly or bi-monthly dosing intervals. Detailed PK parameters are available from clinical trial data.
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| Toxicity/Toxicokinetics |
UBX1325 has been evaluated in Phase 2 clinical trials for diabetic macular edema (DME) and neovascular AMD. The BEHOLD trial for DME and ENVISION trial for nAMD have demonstrated efficacy in improving best-corrected visual acuity (BCVA) and retinal function. The compound is generally well tolerated, with the most common adverse events being mild and transient intraocular inflammation. No significant systemic toxicities have been reported at therapeutic doses. Formal toxicology studies confirm a favorable safety profile in preclinical species.
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| References | |
| Additional Infomation |
UBX1325 is currently in clinical development for the treatment of DME and nAMD and is not yet approved for marketing. The compound was granted Fast Track designation by the FDA for the treatment of DME. Phase 2 results showed that a single injection improved BCVA and reduced retinal thickness, with effects lasting up to 6 months. UBX1325 represents a novel senolytic approach to treating ocular diseases, distinct from anti-VEGF therapies that only block angiogenesis. The compound is for research use only.
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| Molecular Formula |
C53H59CLF3N6O10PS3
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|---|---|
| Molecular Weight |
1159.68674015999
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| Exact Mass |
1158.283
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| CAS # |
2271269-01-1
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| PubChem CID |
147562879
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| Appearance |
White to light yellow solid powder
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| LogP |
7.6
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
19
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| Rotatable Bond Count |
20
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| Heavy Atom Count |
77
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| Complexity |
2160
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| Defined Atom Stereocenter Count |
1
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| SMILES |
N1(C(C)C)C(C2=CC=C(Cl)C=C2)=C(C2=CC=CC(N3CCN(C4=CC=C(NS(C5=CC=C(N[C@@H](CSC6=CC=CC=C6)CCN6CCC(OP(O)(O)=O)CC6)C(S(C(F)(F)F)(=O)=O)=C5)(=O)=O)C=C4)CC3)=C2)C(C(O)=O)=C1C
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| InChi Key |
FSZILRQCEAUYPL-VQJSHJPSSA-N
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| InChi Code |
InChI=1S/C53H59ClF3N6O10PS3/c1-35(2)63-36(3)49(52(64)65)50(51(63)37-12-14-39(54)15-13-37)38-8-7-9-43(32-38)62-30-28-61(29-31-62)42-18-16-40(17-19-42)59-77(71,72)46-20-21-47(48(33-46)76(69,70)53(55,56)57)58-41(34-75-45-10-5-4-6-11-45)22-25-60-26-23-44(24-27-60)73-74(66,67)68/h4-21,32-33,35,41,44,58-59H,22-31,34H2,1-3H3,(H,64,65)(H2,66,67,68)/t41-/m1/s1
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| Chemical Name |
5-(4-chlorophenyl)-2-methyl-4-[3-[4-[4-[[4-[[(2R)-1-phenylsulfanyl-4-(4-phosphonooxypiperidin-1-yl)butan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylamino]phenyl]piperazin-1-yl]phenyl]-1-propan-2-ylpyrrole-3-carboxylic acid
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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 Note: Please store this product in a sealed and protected environment, 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)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~86.23 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.16 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8623 mL | 4.3115 mL | 8.6230 mL | |
| 5 mM | 0.1725 mL | 0.8623 mL | 1.7246 mL | |
| 10 mM | 0.0862 mL | 0.4311 mL | 0.8623 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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