| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg | |||
| Other Sizes |
| Targets |
Mcl-1
Mcl1-IN-2 selectively targets myeloid cell leukemia-1 (Mcl-1), a key anti-apoptotic protein belonging to the Bcl-2 family. Overexpression of Mcl-1 is associated with cancer cell survival and chemotherapy resistance. Additionally, this compound inhibits New Delhi metallo-β-lactamase (NDM-1) in a non-competitive manner, with IC50 values of 0.4637 μM against NDM-1, 3.980 μM against IMP-4, 0.2287 μM against ImiS, and 1.158 μM against L1. The dual targeting of both apoptosis regulation and antimicrobial resistance pathways makes this compound a unique research tool. |
|---|---|
| ln Vitro |
Mcl1-IN-2 (Compound 2) is a Mcl-1 inhibitor[1]. With an IC50 value of 0.4637 M at a concentration of 20 μg/mL, IMB-XH is eliminated from further testing. E. coli BL21(DE3)(pET-30a(+)-NDM-1) can become more ampicillin sensitive by more than 8 times when IMB-XH1 (20 μg/mL) is added. metallo-β-lactamases (MBLs) may be inhibited by a wide range of substances, including IMB-XHI. It may be possible to treat infections brought on by Gram-negative pathogens that are carbapenem-resistant and positive for metallo-β-lactamases by combining IMB-XH1 and Meropenem (MEM)[2].
In vitro studies demonstrate that Mcl1-IN-2 functions as a Mcl-1 inhibitor. At a concentration of 20 μg/mL, IMB-XH (related compound) showed an IC50 value of 0.4637 M and was eliminated from further testing. The compound significantly increases ampicillin sensitivity in E. coli BL21(DE3)(pET-30a(+)-NDM-1) by more than 8-fold when added at 20 μg/mL. Metallo-β-lactamases (MBLs) are inhibited by IMB-XH1, suggesting potential for treating carbapenem-resistant Gram-negative pathogens when combined with meropenem. The compound shows promise in overcoming drug resistance in cancer cells by inducing apoptosis through Mcl-1 inhibition. |
| ln Vivo |
In vivo efficacy data for Mcl1-IN-2 is currently limited in the available literature. However, based on its mechanism as a Mcl-1 inhibitor and NDM-1 inhibitor, the compound is expected to demonstrate activity in animal models of cancer and bacterial infection. The combination of IMB-XH1 with meropenem may offer a therapeutic strategy for treating infections caused by carbapenem-resistant, metallo-β-lactamase-positive Gram-negative pathogens. Further in vivo studies are warranted to fully characterize its pharmacokinetic and pharmacodynamic profiles in animal disease models.
|
| Enzyme Assay |
The in vitro enzyme/receptor binding assay for Mcl1-IN-2 involves testing against metallo-β-lactamases including NDM-1, IMP-4, ImiS, and L1. IC50 values are determined using standard enzymatic inhibition assays, with reported values of 0.4637 μM for NDM-1, 3.980 μM for IMP-4, 0.2287 μM for ImiS, and 1.158 μM for L1. The compound is a non-competitive inhibitor of NDM-1. For Mcl-1 binding, standard competitive binding assays using fluorescently labeled Mcl-1 ligands or surface plasmon resonance (SPR) can be employed to determine binding affinity and inhibition constants.
|
| Cell Assay |
In vitro cellular assays for Mcl1-IN-2 typically involve culturing cancer cell lines that overexpress Mcl-1. Cells are treated with varying concentrations of the compound (typically 0.1-100 μM range) for 24-72 hours. Cell viability is assessed using MTT, CCK-8, or ATP-lite assays to determine IC50 values. Apoptosis induction is evaluated through caspase-3/7 activity assays, Annexin V-FITC/PI double staining, and Western blot analysis of PARP cleavage and Bcl-2 family protein expression. For antibacterial assays, E. coli BL21(DE3)(pET-30a(+)-NDM-1) is treated with 20 μg/mL compound to assess changes in ampicillin sensitivity.
|
| Animal Protocol |
In vivo animal studies for Mcl1-IN-2 would typically involve mouse xenograft models using human cancer cell lines with high Mcl-1 expression. Tumor-bearing mice are administered the compound via oral gavage or intraperitoneal injection at doses ranging from 10-100 mg/kg, daily or on a scheduled basis. Tumor volume and body weight are monitored over 2-4 weeks. For infection models, mice infected with carbapenem-resistant NDM-1-positive pathogens would be treated with the compound alone or in combination with meropenem. Endpoints include bacterial load reduction, survival rate, and histopathological analysis of infected tissues.
|
| ADME/Pharmacokinetics |
Published pharmacokinetic data for Mcl1-IN-2 is currently limited. Based on its physicochemical properties (LogP 3.42, molecular weight 333.4, hydrogen bond donors 2, acceptors 5), the compound is expected to have moderate lipophilicity and reasonable membrane permeability. The compound shows good stability as a solid powder and is typically stored at -20°C for long-term preservation. For in vivo studies, formulation in suitable vehicles such as DMSO, PEG400, or saline-based solutions would be required. Further PK studies including plasma half-life, clearance, volume of distribution, and oral bioavailability need to be conducted.
|
| Toxicity/Toxicokinetics |
Toxicological data for Mcl1-IN-2 is not extensively reported in the available literature. As a research compound intended for laboratory use only, it is not approved for human clinical applications. Standard safety precautions should be followed when handling this compound, including the use of personal protective equipment. The compound is classified for research use only and should not be used for therapeutic, diagnostic, or other human purposes. For detailed toxicity profiles, including acute toxicity, genotoxicity, and organ-specific toxicity, specialized toxicological studies would need to be performed in appropriate animal models.
|
| References | |
| Additional Infomation |
Mcl1-IN-2 (also known as IMB-XH1) is a research-grade compound with a purity of ≥98%. Its CAS number is 292057-76-2 and molecular formula is C19H15N3OS. The compound appears as a white to yellow solid powder and has a density of 1.4±0.1 g/cm³, boiling point of 557.5±45.0 °C, and LogP of 3.42. The mechanism of action involves dual inhibition of Mcl-1 (apoptosis pathway) and NDM-1 (antibacterial resistance). This compound has not advanced to clinical trials and is not FDA-approved. It is strictly for research purposes only.
|
| Molecular Formula |
C19H15N3OS
|
|---|---|
| Molecular Weight |
333.4
|
| Exact Mass |
333.093
|
| Elemental Analysis |
C, 68.45; H, 4.53; N, 12.60; O, 4.80; S, 9.62
|
| CAS # |
292057-76-2
|
| Related CAS # |
292057-76-2
|
| PubChem CID |
3625042
|
| Appearance |
White to yellow solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Boiling Point |
557.5±45.0 °C at 760 mmHg
|
| Flash Point |
290.9±28.7 °C
|
| Vapour Pressure |
0.0±1.6 mmHg at 25°C
|
| Index of Refraction |
1.755
|
| LogP |
3.42
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
24
|
| Complexity |
410
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
OC1=C(N=CC=C2)C2=CC=C1C(NC3=CC=CC=N3)C4=CC=CS4
|
| InChi Key |
ICJKSTJCIAGPIS-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C19H15N3OS/c23-19-14(9-8-13-5-3-11-21-17(13)19)18(15-6-4-12-24-15)22-16-7-1-2-10-20-16/h1-12,18,23H,(H,20,22)
|
| Chemical Name |
7-[(pyridin-2-ylamino)-thiophen-2-ylmethyl]quinolin-8-ol
|
| Synonyms |
Mcl1-inhibitor-2; Mcl1 inhibitor 2; Mcl1-IN-2; Mcl1IN2; Mcl1 IN 2
|
| 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) |
DMSO: ~33.3 mg/mL (~100.0 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (6.24 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 sonication.
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. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.24 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 20.8 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: ≥ 2.08 mg/mL (6.24 mM) (saturation unknown) in 10% DMSO + 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 | 2.9994 mL | 14.9970 mL | 29.9940 mL | |
| 5 mM | 0.5999 mL | 2.9994 mL | 5.9988 mL | |
| 10 mM | 0.2999 mL | 1.4997 mL | 2.9994 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
