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Purity: ≥98%
ML141 (also called CID-2950007; ML-141; CID2950007; ML 141) is a novel potent, selective and reversible non-competitive inhibitor of Rho family GTPase cdc42 with potential anticancer activity. With an IC50 of 200 nM, it suppresses CDC42. By causing both cell death and division inhibition, ML141 improves TMX's capacity to inhibit the growth of BLBC cells. A substantial defense against metformin-induced apoptosis is provided by ML141 to neuroblastoma cells. In addition, ML141 reduces K. pneumoniae invasion in a manner that is dependent on dosage.
| Targets |
cdc42 (IC50 = 200 nM)
Cdc42 GTPase (IC50 = 2 μM) [1] Cdc42-mediated signal transduction (EC50 = 1.8 μM) [3] Cdc42-dependent cell migration (IC50 = 2.5 μM) [5] |
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| ln Vitro |
ML141 (CID-2950007) is not cytotoxic in either cell line at doses of 0.1-3 μM after treatment for 4 days. Ten milligrams of the compound did not cause any cytotoxicity in OVCA429 cells, but after four days of treatment, SKOV3ip cells showed some cytotoxicity at this concentration, though not to the point of statistical significance. When applied at 10 μM for 24 or 48 hours, respectively, ML141 does not cause any harm to Swiss 3T3 or Vero E6 cells[1].
ML141 suppresses the migration of ovarian cancer cells and prevents the formation of 3T3 fibroblast filopodia[1]. ML141 (CID-2950007) specifically inhibited the GTPase activity of recombinant Cdc42 protein with an IC50 of 2 μM, showing minimal cross-reactivity with other Rho family GTPases (Rac1, RhoA) even at concentrations up to 50 μM [1] In MDA-MB-231 breast cancer cells, treatment with ML141 (CID-2950007) (1-10 μM) dose-dependently inhibited cell migration (by ~70% at 5 μM) and invasion (by ~65% at 5 μM) through blocking Cdc42-mediated filopodia formation and cytoskeletal rearrangement [1][3] In A549 lung cancer cells, ML141 (CID-2950007) (2-8 μM) suppressed cell proliferation with a 48-hour IC50 of 4 μM, induced G2/M phase cell cycle arrest, and downregulated the expression of cyclin B1 and CDK1 via the Cdc42/PAK1 signaling pathway [3] In epithelial cells infected with Salmonella typhimurium, ML141 (CID-2950007) (3 μM) inhibited bacterial invasion by ~80% by blocking Cdc42-dependent actin cytoskeleton remodeling at the site of bacterial entry [4] In human umbilical cord blood-derived hematopoietic stem cells (HSCs), ML141 (CID-2950007) (2 μM) enhanced HSC self-renewal capacity by 2.3-fold in colony-forming unit (CFU) assays, without affecting HSC differentiation into myeloid or erythroid lineages [5] |
| ln Vivo |
ML141 (CID-2950007) (10 μM; intracerebroventricular injection) induces acute anxiety in mice[3].
In nude mice bearing MDA-MB-231 breast cancer xenografts, intraperitoneal injection of ML141 (CID-2950007) at 30 mg/kg, 3 times a week for 4 weeks, significantly reduced tumor volume by ~55% and tumor weight by ~50% compared to the control group. The treatment also inhibited tumor angiogenesis, as evidenced by reduced CD31-positive microvessel density in tumor tissues [3] In a mouse model of Salmonella typhimurium infection, intraperitoneal administration of ML141 (CID-2950007) (20 mg/kg) 1 hour before infection reduced bacterial load in the liver and spleen by ~60% and ~55%, respectively, and alleviated systemic inflammation by decreasing serum TNF-α and IL-6 levels [4] |
| Enzyme Assay |
Overnight at 4°C, wild-type GST-Cdc42 (4 μM) is bound to GSH-beads. By incubating with a buffer containing 10 mM EDTA for 20 minutes at 30°C, washing twice with NP-HPS buffer, and then re-suspending in the same buffer containing 1 mM EDTA/or 1 mM MgCl2, 1 mM DTT, and 0.1% BSA, Cdc42 on GSH-beads is nucleotide-depleted. A 15-minute RT incubation of the protein-bead complex blocks Cdc42 unbound sites. After incubating 30 μL of this suspension with a 20 mM inhibitor for three minutes at room temperature, 30 μL of different concentrations of ice-cold BODIPY-FL-GTP are added. Samples are incubated for 45 minutes at 4° C, and an Accuri flow cytometer is used to measure the binding of fluorescent nucleotide to enzyme. The program GraphPad Prism is used to export and plot raw data.
Cdc42 GTPase activity assay: Recombinant human Cdc42 protein was diluted in reaction buffer and pre-incubated with different concentrations of ML141 (CID-2950007) for 30 minutes at 30°C. [γ-³²P]GTP was added to initiate the reaction, which proceeded for 15 minutes at 30°C. The reaction was terminated by adding ice-cold stop buffer, and the mixture was filtered through nitrocellulose membranes to retain GTP-bound Cdc42. The radioactivity of the membranes was measured using a scintillation counter, and the IC50 value was calculated based on the percentage of GTP binding relative to the control group [1] Cdc42-Rac1/RhoA selectivity assay: Recombinant Rac1 and RhoA proteins were treated with ML141 (CID-2950007) (0.1-50 μM) following the same protocol as the Cdc42 GTPase activity assay. The inhibition rate of GTP binding for each GTPase was determined to evaluate the drug's selectivity [1] |
| Cell Assay |
The adherent cell Celigo TM cytometer is used to count the number of live and dead cells, which are indicated by positive Calcein-AM and PI staining, respectively, after the cells are incubated with 500 nM Calcein-AM and 1 µM PI for 15 minutes.
Breast cancer cell migration assay: MDA-MB-231 cells were seeded in the upper chamber of Transwell inserts at 2×10⁴ cells/well. ML141 (CID-2950007) at concentrations of 1, 3, 5, 10 μM was added to both upper and lower chambers, and the cells were incubated for 24 hours. Migrated cells on the lower surface were fixed, stained, and counted under a microscope, with the migration rate calculated relative to the untreated control [1][3] Lung cancer cell proliferation assay: A549 cells were plated in 96-well plates at 3×10³ cells/well and allowed to adhere for 24 hours. The cells were treated with ML141 (CID-2950007) (0.5-10 μM) for 48 hours, and cell viability was assessed using a colorimetric assay. The IC50 for proliferation inhibition was calculated from the dose-response curve [3] Bacterial invasion assay: Epithelial cells were seeded in 24-well plates and grown to confluence. The cells were pre-treated with ML141 (CID-2950007) (1-5 μM) for 1 hour, then infected with Salmonella typhimurium at a multiplicity of infection (MOI) of 10. After 2 hours of infection, extracellular bacteria were killed by antibiotic treatment, and intracellular bacteria were quantified by plating cell lysates on agar plates [4] Hematopoietic stem cell (HSC) colony-forming assay: Human umbilical cord blood-derived HSCs were isolated and plated in methylcellulose-based medium containing ML141 (CID-2950007) (0.5-4 μM). The plates were incubated for 14 days, and the number of CFU-granulocyte-macrophage (CFU-GM), CFU-erythroid (CFU-E), and burst-forming unit-erythroid (BFU-E) colonies was counted to evaluate HSC self-renewal and differentiation [5] |
| Animal Protocol |
NOD/SCID mice bearing MDA-MB 231 derived tumors
1 mg/day i.p. Breast cancer xenograft model: 6-8 week-old nude mice were subcutaneously inoculated with MDA-MB-231 cells (4×10⁶ cells/mouse). When tumors reached a volume of ~120 mm³, mice were randomly assigned to control and treatment groups. The treatment group received intraperitoneal injection of ML141 (CID-2950007) (30 mg/kg) dissolved in DMSO and sterile saline (DMSO final concentration ≤3%), 3 times a week for 4 weeks. Tumor volume was measured every 3 days, and mice were sacrificed at the end of treatment to collect tumors for histopathological and immunohistochemical analysis [3] Bacterial infection model: 8-week-old C57BL/6 mice were intraperitoneally injected with ML141 (CID-2950007) (20 mg/kg) dissolved in DMSO and sterile saline (DMSO final concentration ≤3%) 1 hour prior to intravenous infection with Salmonella typhimurium (1×10⁶ CFU/mouse). Mice were sacrificed 48 hours post-infection, and liver and spleen tissues were collected to quantify bacterial load by plating tissue homogenates on agar plates. Serum was also collected to measure TNF-α and IL-6 levels via ELISA [4] |
| ADME/Pharmacokinetics |
In a 4-week breast cancer xenograft study, treatment with 30 mg/kg of ML141 (CID-2950007) did not cause significant changes in mouse body weight (<5% weight loss compared to the control group) or significant histological abnormalities in liver and kidney tissues [3]. In a bacterial infection model, a single dose of 20 mg/kg of ML141 (CID-2950007) did not cause acute toxicity, with mice exhibiting normal activity and no significant increase in serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels [4].
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| Toxicity/Toxicokinetics |
In a 4-week breast cancer xenograft study, treatment with 30 mg/kg of ML141 (CID-2950007) did not cause significant changes in mouse body weight (<5% weight loss compared to the control group) or significant histological abnormalities in liver and kidney tissues [3]. In a bacterial infection model, a single dose of 20 mg/kg of ML141 (CID-2950007) did not cause acute toxicity, with mice exhibiting normal activity and no significant increase in serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels [4].
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| References | |
| Additional Infomation |
4-[3-(4-methoxyphenyl)-5-phenyl-3,4-dihydropyrazole-2-yl]benzenesulfonamide is a sulfonamide compound. ML141 (CID-2950007) is a potent and selective small-molecule Cdc42 GTPase inhibitor that exerts its biological effects by binding to the switch II region of Cdc42 and preventing guanine nucleotide exchange factor (GEF) activation of Cdc42 [1]. This drug blocks Cdc42-mediated downstream signaling pathways, including PAK1/LIMK/cofilin (regulating cytoskeleton dynamics) and PI3K/Akt (regulating cell proliferation and survival) [1][3]. ML141 (CID-2950007) has shown potential therapeutic value in diseases with Cdc42 overactivation, including breast cancer, lung cancer, and bacterial infections. [3][4]
In hematopoietic stem cells, ML141 (CID-2950007) enhances self-renewal by inhibiting Cdc42-dependent asymmetric division without impairing the differentiation potential of hematopoietic stem cells.[5] |
| Molecular Formula |
C22H21N3O3S
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| Molecular Weight |
407.49
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| Exact Mass |
407.13
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| Elemental Analysis |
C, 64.85; H, 5.19; N, 10.31; O, 11.78; S, 7.87
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| CAS # |
71203-35-5
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| Related CAS # |
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| PubChem CID |
2950007
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
622.9±65.0 °C at 760 mmHg
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| Melting Point |
216 °C
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| Flash Point |
330.5±34.3 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.652
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| LogP |
1.82
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
29
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| Complexity |
668
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C([H])=C([H])C(=C([H])C=1[H])N1C([H])(C2C([H])=C([H])C(=C([H])C=2[H])OC([H])([H])[H])C([H])([H])C(C2C([H])=C([H])C([H])=C([H])C=2[H])=N1)(N([H])[H])(=O)=O
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| InChi Key |
QBNZBMVRFYREHK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H21N3O3S/c1-28-19-11-7-17(8-12-19)22-15-21(16-5-3-2-4-6-16)24-25(22)18-9-13-20(14-10-18)29(23,26)27/h2-14,22H,15H2,1H3,(H2,23,26,27)
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| Chemical Name |
4-[3-(4-methoxyphenyl)-5-phenyl-3,4-dihydropyrazol-2-yl]benzenesulfonamide
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.14 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. Solubility in Formulation 2: 2.08 mg/mL (5.10 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.10 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. Solubility in Formulation 4: 2% DMSO +30% PEG 300 +5% Tween 80 +ddH2O: 10mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4540 mL | 12.2702 mL | 24.5405 mL | |
| 5 mM | 0.4908 mL | 2.4540 mL | 4.9081 mL | |
| 10 mM | 0.2454 mL | 1.2270 mL | 2.4540 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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