| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg | |||
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| Targets |
Target: PERK/eIF2alpha/CHOP pathway (UPR apoptotic arm). ML291 activates PERK (PKR-like ER kinase), leading to eIF2alpha phosphorylation, which suppresses global protein synthesis while paradoxically promoting translation of ATF4 and subsequent CHOP (DDIT3) expression. CHOP drives a pro-apoptotic transcriptional program, overwhelming the adaptive capacity of the UPR and causing apoptosis in cancer cells.
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| ln Vitro |
In vitro, ML291 activates the PERK/eIF2alpha/CHOP pathway with an EC50 of 762 nM, inducing apoptosis in a variety of solid cancer cell lines (breast, lung, colon, pancreatic, prostate). It reduces the viability of leukemia cells (EC50 ~1-10 uM depending on cell line) and triggers CHOP-dependent apoptosis. It has 105-fold selectivity for activating the apoptotic UPR arm over the adaptive IRE1alpha/XBP1 arm.
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| ln Vivo |
No in vivo efficacy data have been published specifically for ML291 in animal models. Based on its mechanism, it is expected to reduce tumor growth in xenograft models of solid tumors and leukemia. Preclinical studies indicate it reduces leukemia cell burden and induces tumor regression, but detailed animal efficacy data remain to be published in peer-reviewed literature.
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| Enzyme Assay |
For cell-free PERK kinase activity assays: recombinant PERK protein (kinase domain) is incubated with varying concentrations of ML291 (0-10 uM), 1 mM ATP, and recombinant eIF2alpha substrate protein in kinase buffer for 30-60 min at 30degC. Phosphorylation of eIF2alpha (Ser51) is detected by Western blot with phospho-specific antibodies or by in vitro kinase assay using 32P-ATP, with quantitation by autoradiography or scintillation counting. EC50 is calculated from dose-response curves.
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| Cell Assay |
For cell-based assays: cancer cell lines (e.g., A549 lung, MCF7 breast, HCT116 colon, Panc-1 pancreatic cancer, K562 or HL-60 leukemia) are seeded in 96-well plates and treated with ML291 (0.1-100 uM, 24-72 h). Cell viability is assessed by MTT or CellTiter-Glo assay. Apoptosis is measured by Annexin V/PI flow cytometry and caspase-3/7 activity assays. CHOP, ATF4, and phospho-eIF2alpha (Ser51) levels are measured by Western blot. LC3 puncta formation is assessed by immunofluorescence for autophagy markers.
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| Animal Protocol |
For in vivo animal studies: potential protocol involves xenograft mouse models bearing human solid tumors (e.g., A549 lung cancer, HCT116 colon cancer) or disseminated leukemia models. ML291 would be administered intraperitoneally or orally (20-100 mg/kg) daily for 2-3 weeks. Tumor volume is measured by calipers, survival is recorded, and tumor tissues are harvested for Western blot analysis of CHOP, p-eIF2alpha, and cleaved caspase-3. Bone marrow from leukemia models would be analyzed for leukemia cell burden by flow cytometry.
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| ADME/Pharmacokinetics |
PK properties of ML291: For a small molecule UPR inducer (MW 413.83, solubility in DMSO 100 mg/mL), predicted PK properties in rodents after oral or IP administration: moderate oral bioavailability (∼30-50%), Tmax 1-2 h, plasma half-life 4-8 h. The compound is soluble in DMSO, and in vivo formulation can be prepared using DMSO:PEG300:Saline (10:40:50). No formal PK studies have been published.
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| Toxicity/Toxicokinetics |
No toxicity data have been reported for ML291. Based on its mechanism, activation of the PERK/eIF2alpha/CHOP apoptotic pathway may cause toxicity in normal tissues with high protein synthesis demands, such as the pancreas, liver, and gastrointestinal tract. The compound has 105-fold selectivity for activating the apoptotic arm over the adaptive arm, suggesting a therapeutic window, but no formal toxicity studies have been published.
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| References | |
| Additional Infomation |
ML291 is a research compound not yet approved for clinical use. It is a valuable first-in-class chemical probe for studying the unfolded protein response (UPR) and its role in cancer biology, particularly the balance between adaptive and apoptotic UPR signaling. It has potential as a lead compound for developing UPR-targeted cancer therapeutics, especially for solid tumors that rely on adaptive UPR for survival, and for leukemia research.
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| Molecular Formula |
C16H16CLN3O6S
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|---|---|
| Molecular Weight |
413.832741737366
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| Exact Mass |
413.044
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| CAS # |
1523437-16-2
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| PubChem CID |
52940465
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.6±0.1 g/cm3
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| Index of Refraction |
1.652
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| LogP |
2.78
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
27
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| Complexity |
648
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
XKMLYHZJKCRLOI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H16ClN3O6S/c17-11-7-9-19(10-8-11)27(24,25)13-3-1-12(2-4-13)18-16(21)14-5-6-15(26-14)20(22)23/h1-6,11H,7-10H2,(H,18,21)
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| Chemical Name |
N-[4-(4-chloropiperidin-1-yl)sulfonylphenyl]-5-nitrofuran-2-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 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)
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| Solubility (In Vitro) |
DMSO : ≥ 50 mg/mL (~120.82 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4165 mL | 12.0823 mL | 24.1645 mL | |
| 5 mM | 0.4833 mL | 2.4165 mL | 4.8329 mL | |
| 10 mM | 0.2416 mL | 1.2082 mL | 2.4165 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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