| Field | Specification |
|---|---|
| Target | |
| Alternative names | ZGN-1061 |
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C26H42N2O6 |
| Purity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
Aclimostat (ZGN-1061) is a methionine aminopeptidase 2 (MetAP2) inhibitor with anti-obesity, anti-diabetic, and ovarian cancer-related activities that does not readily distribute to the central nervous system. It acts on the active site of MetAP2 through irreversible covalent binding, blocking enzyme activity via interactions with His231 and His339. It regulates gene expression and reduces fat mass, plasma glucose, insulin, LDL-C, hs-CRP, and leptin levels while increasing adiponectin, and can be used in research on type 2 diabetes, overweight, obesity, and ovarian cancer[1][2][3][4][5]. It is supplied as a white to off-white solid (C26H42N2O6, MW 478.62) at 98.0% purity.
Physical & Chemical Properties
| CAS Number | 2082752-83-6 |
|---|---|
| Molecular Formula | C26H42N2O6 |
| Molecular Weight | 478.62 g/mol |
| Purity | 98.0% |
| Appearance | Solid |
| Color | White to off-white |
| SMILES | C[C@]1([C@H](O1)C/C=C(C)\C)[C@]2([H])[C@]3(CC[C@H]([C@H]2OC)OC(N4CC(C4)CCN5CCOCC5)=O)CO3 |
| Target | MetAp2 |
| Signaling Pathway | Metabolic Enzyme/Protease |
| Solubility | In Vitro: DMSO: 230 mg/mL (480.55 mM; Requires sonication; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) |
| Storage | 4°C, stored under nitrogen. In solvent: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with the Safety Data Sheet and your institution's chemical hygiene plan.
In Vitro
| Solvent | Solubility | Notes |
|---|---|---|
| DMSO | 230 mg/mL (480.55 mM) | requires sonication; use freshly opened DMSO (absorbed moisture lowers solubility) |
Aliquot the stock solution and store it at -80°C (up to 6 months) or -20°C (up to 1 month); stored under nitrogen; avoid repeated freeze-thaw cycles.
Data provided by the manufacturer.
In Vitro
Aclimostat (ZGN-1061) (6 nM; 2-24 h) induces gene expression changes nearly identical to those of Beloranib in HepG2 cells following exposures of 2 hours and 24 hours to 6 nM, and show high concordance across genes tied to metabolic efficacy[2]. Aclimostat (1-72 h) suppresses HUVEC proliferation, with an EC50 of 0.24 nM following 72 hours of continuous exposure, but proliferation is unaffected by brief exposures (4 hours or less) at up to 50× the EC50[2]. In HUVECs, Aclimostat (10 nM; 2 h, assessed over 72 h post-washout) displays transient target engagement: covalent binding to the MetAP2 active site declines over 72 hours after a 2-hour 10 nM exposure, and the MetAP2 substrate THX 1-6 does not accumulate in a sustained manner[2]. In HepG2 cells, Aclimostat (10 nM; 2 h, assessed over 72 h post-washout) likewise shows transient target engagement; 72 hours after a 2-hour exposure to 10 nM, covalent binding at the MetAP2 active site has declined[2]. ZGN-1061 shows strong binding to human MetAP2 (docking score of -7.2 kcal/mol) and interacts with key active site residues that are critical for MetAP2 function[5]. In HUVECs, Aclimostat (1-20 nM; 4-72 h) raises p21 and lowers TM protein levels, but leaves these proteins unchanged with shorter exposures of 4 hours or 8 hours, and leaves p53, vWF, and PAI-1 levels unchanged across all tested concentrations and times[2]. ZGN-1061 (0-5000 nM; 1-6 days) suppresses proliferation in A2780 and SKOV3 ovarian cancer cells; efficacy is enhanced, with lower IC50 values, in METAP2-overexpressing SKOV3 cells than in control SKOV3 cells, and attenuated in METAP2-knockdown A2780 cells relative to control A2780 cells[3].
ELISA Assay[2]
| Cell Line | HUVEC (human umbilical vein endothelial cell) |
|---|---|
| Concentration | 1 nM, 10 nM, 20 nM |
| Incubation Time | 4 h; 8 h; 72 h |
| Result | Did not alter p53 or von Willebrand factor (vWF) protein levels at any concentration or incubation time. Increased p21 and reduced thrombomodulin (TM) protein levels at all concentrations after 72-hour incubation. Showed no meaningful changes in p21 and TM protein levels with 4-hour or 8-hour incubations. Had no effect on plasminogen activator inhibitor-1 (PAI-1) protein levels at any concentration or time point. |
Cell Proliferation Assay[3]
| Cell Line | A2780 ovarian cancer cells (control and METAP2-knockdown), SKOV3 ovarian cancer cells (control and METAP2-overexpressing) |
|---|---|
| Concentration | 0-5000 nM |
| Incubation Time | 1-6 days |
| Result | Significantly inhibited proliferation in control A2780 cells. Showed attenuated inhibitory effect in METAP2-knockdown A2780 cells. Exhibited enhanced anti-proliferative activity in METAP2-overexpressing SKOV3 cells compared to control SKOV3 cells. Reduced IC50 values in METAP2-overexpressing SKOV3 cells relative to control SKOV3 cells. |
In Vivo
In DIO insulin-resistant mice, Aclimostat (ZGN-1061) (0.3 mg/kg; s.c.; daily; 4 weeks) yields a 25% body weight reduction, improved glycemic control, and favorable metabolic changes[2]. In diet-induced obese insulin-resistant mice, ZGN-1061 (s.c.; daily; 28 days) lowers body weight by 25% and improves glucose and insulin levels[5]. In healthy beagle dogs, Aclimostat (2 mg/kg, s.c., every 3 days for 10 days) shows good tolerability, with no adverse effects on coagulation markers or hematology parameters[2]. In Sprague Dawley rats, Aclimostat (2-25 mg/kg, s.c., every 3 days for 28 days) is well tolerated, with minimal, reversible toxic effects[2]. In subcutaneous xenograft models, Aclimostat (0.1 mg/kg; s.c.; every 3 days; 4 weeks) shows potent activity against ovarian cancer, with significantly enhanced efficacy in METAP2-overexpressing tumors[3].
| Animal Model | C57BL/6J (male, 7 to 8 weeks old at study start, high-fat diet-induced obese model)[2] |
|---|---|
| Dosage | 0.3 mg/kg |
| Administration | s.c.; daily; 4 weeks |
| Result | Reduced body weight by 25%, primarily due to reduced fat mass. Significantly increased percent lean mass relative to vehicle at Weeks 2 and 4. Reduced mean daily energy intake to 0.35 kJ/g lean mass at Week 2, comparable to vehicle levels by Week 4. Improved fasting glucose and insulin levels, with a statistically significant reduction in HOMA-IR index relative to vehicle. Produced statistically significant reductions in low-density and high-density lipoprotein cholesterol, alongside increased β-hydroxybutyrate levels and reduced leptin levels. Increased target engagement (measured by N-terminal methionine of thioredoxin [THX 1-6]) from below the limit of detection to a level comparable to beloranib. |
| Animal Model | Beagle (male, 10 to 20 months old)[2] |
|---|---|
| Dosage | 2 mg/kg |
| Administration | s.c.; every 3 days; 10 days |
| Result | Produced no adverse changes in clinical observations, hematology (including platelet count), or coagulation markers (D-dimer, thrombin time, antithrombin III). Caused weight loss over the study period, but food intake remained unchanged, and all animals survived the scheduled dosing period. |
| Animal Model | Sprague Dawley (male and female, 9−10 weeks old)[2] |
|---|---|
| Dosage | 2 mg/kg; 6 mg/kg; 25 mg/kg |
| Administration | s.c.; every 3 days; 28 days |
| Result | Observed no mortality at any dose tested. Showed the highest dose (25 mg/kg) was well tolerated, with increased injection site irritation and inflammation that largely resolved after the 10-week recovery period (minimal fibrosis noted in 3/10 rats). Produced minimal, low-incidence findings including mixed cell inflammation in the lung and individual hepatocellular necrosis, which resolved after dosing ceased. At the no observed adverse effect level (NOAEL), produced repeat-dose AUC0-t values of 409 ng×h/mL (males) and 288 ng×h/mL (females), with Cₘₐₓ values 21- to 52-fold higher than beloranib at its respective NOAEL. |
| Animal Model | BALB/c nude (female)[3] |
|---|---|
| Dosage | 0.1 mg/kg |
| Administration | s.c.; every 3 days; 4 weeks |
| Result | Markedly suppressed tumor progression, with significantly greater efficacy observed in METAP2-overexpressing xenografts. Showed significantly higher tumor weight inhibition in METAP2-overexpressing xenografts compared to control xenografts. Was well-tolerated with no significant body weight changes or signs of toxicity. |
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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