BCL-XL-IN-3
Based on 1 Customer Validation
BCL-XL-IN-3 is a cell-impermeable BCL-XL inhibitor with a Ki of 16 pM. BCL-XL-IN-3 disrupts the critical hydrogen bond network via methylation of the nitrogen atom on the P2-binding amide bond, resulting in complete loss of cellular activity against BCL-XL. BCL-XL-IN-3 can be used in non-small cell lung cancer and cancer-related research.
For research use only. We do not sell to patients.
- CAS No.: 1949840-87-2
- Formula: C46H55N7O6S
- Molecular Weight:834.04
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Storage:
-20°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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BCLxL 16 pM (Ki) |
BCL-XL-IN-3 (compound 11) potently binds to recombinant BCL-XL protein with a Ki of <0.01 nM[1].
BCL-XL-IN-3 (compound 1.85) is a high-affinity Bcl-xL inhibitor with a Ki value in the picomolar range (0.016 nM); while serum protein binding reduces its activity approximately 25-fold (0.4 nM), it retains high affinity in the nanomolar range[2].
BCL-XL-IN-3 (48 h) exhibits an EC50 of 78 nM against Molt-4 cells in the presence of 10% human serum, demonstrating moderate cytotoxic activity[2].
BCL-XL-IN-3 (0.020-5 μM; 48 h) inhibits the viability of BCL-XL-dependent Molt-4 human acute lymphoblastic leukemia cells with an EC50 of 77.8 nM after 48 hours of incubation[1].
BCL-XL-IN-3 (1-3 h) induces mitochondrial depolarization in Digitonin (HY-N4000)-permeabilized Molt-4 human acute lymphoblastic leukemia cells with an EC50 of 0.07 nM, indicating potent intrinsic BCL-XL inhibitory activity independent of cell permeability[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human acute lymphoblastic leukemia Molt-4 cells
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Concentration:0.020-5 μM
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Incubation Time:48 h
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Result:Inhibited Molt-4 cell viability with an EC50 of 77.8 nM.
BCL-XL-IN-3 delivered as AM1-25 (10-30 mg/kg; i.v.; Q3W×2, Q1W×3) is well tolerated in cynomolgus monkeys at doses up to 30 mg/kg, with reduced renal and hematological toxicity compared to earlier ADC formulations[1].
BCL-XL-IN-3 delivered as AM1-25 (10 mg/kg; i.p.; Q7D×2) induces robust tumor growth inhibition as monotherapy and enhances the efficacy of Docetaxel (HY-B0011) in H1650 xenograft models[1].
BCL-XL-IN-3 (0.01-0.3 mg/kg per minute; i.v. infusion) is well-tolerated in anesthetized dogs at doses up to 0.1 mg/kg per minute (peak plasma concentration 447 ng/mL) but causes cardiovascular collapse at 0.3 mg/kg per minute (peak plasma concentration 1015 ng/mL)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SCID/bg (female, 8-week-old, ~22 g)[1]
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Dosage:30 mg/kg
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Administration:i.v.; single dose
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Result:Showed no significant reduction in platelet counts at 6, 72, and 168 hours post-dosing.
Maintained mean platelet counts near baseline levels (~1300-1500 ×103/μl) through 168 hours.
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Animal Model:SCID/bg (female, 8-week-old, ~22 g)[1]
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Dosage:10 mg/kg
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Administration:i.p.; Q7D×2
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Result:Induced statistically significant tumor growth inhibition (TGI) compared to control as monotherapy.
Enhanced docetaxel's TGI from 83% to 99% when combined with a single intravenous dose of docetaxel (7.5 mg/kg).
Showed significantly increased durability of the response compared to docetaxel alone.
Resulted in only two of eight tumors relapsing to 1000 mm3 within 100 days of combination treatment, versus all tumors relapsing within 46 days with docetaxel monotherapy.\nInduced statistically significant tumor growth inhibition (TGI) compared to control as monotherapy.
Enhanced docetaxel's TGI from 82% to 96% when combined with a single intravenous dose of docetaxel (7.5 mg/kg).
Showed significantly increased durability of the response compared to docetaxel alone.
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Animal Model:Cynomolgus Monkey[1]
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Dosage:10 mg/kg (Q3W×2); 30 mg/kg (Q3W×2); 10 mg/kg (Q1W×3)
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Administration:i.v.; Q3W×2; Q1W×3
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Result:Showed linear pharmacokinetic profiles for total antibody and conjugated antibody across doses.
Reached free payload 11 maximum plasma concentrations (Cmax) of 1.48 ng/mL (10 mg/kg Q3W×2) and 4.71 ng/mL (30 mg/kg Q3W×2) after the second dose.
Exhibited reduced renal toxicity compared to AM1-15, with multifocal rather than diffuse glomerular matrix thickening.
Caused minimal hematological effects: platelet counts decreased by only 19% from baseline at the highest dose (nadir 315,000 platelets/μl), and red blood cell mass decreased by only 5% from baseline.
Showed no cardiovascular toxicity.
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Animal Model:Beagle (anesthetized)[1]
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Dosage:0.01 mg/kg per minute; 0.1 mg/kg per minute; 0.3 mg/kg per minute
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Administration:i.v. infusion
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Result:Showed no impact on blood pressure or other indices of cardiovascular function at doses of 0.01 and 0.1 mg/kg per minute, with a peak plasma concentration of 447 ng/mL at the 0.1 mg/kg per minute dose.
Reached a peak plasma concentration of 1015 ng/mL at the 0.3 mg/kg per minute dose, which produced a notable decrease in mean arterial pressure, contractility, and cardiac output leading to cardiovascular collapse in both animals.
Chemical Information
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CAS No. 1949840-87-2
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Appearance Solid
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Molecular Weight 834.04
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Formula C46H55N7O6S
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Color Light yellow to yellow
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SMILES
O[C@H](CO)CCNCCO[C@](C1)(C2)C[C@@](C[C@@]2(C3)C)(C[C@]13C)CN4C(C)=C(C(C=CC(N(CCC5=CC=C6)CC5=C6C(NC7=NC8=CC=CC=C8S7)=O)=N9)=C9C(O)=O)C=N4
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
-20°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
Solvent & Solubility
DMSO : 100 mg/mL (119.90 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 5 mg/mL (5.99 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 5 mg/mL (5.99 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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Data Sheet (286 KB)
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SDS (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.1990 mL | 5.9949 mL | 11.9898 mL | 29.9746 mL |
| 5 mM | 0.2398 mL | 1.1990 mL | 2.3980 mL | 5.9949 mL | |
| 10 mM | 0.1199 mL | 0.5995 mL | 1.1990 mL | 2.9975 mL | |
| 15 mM | 0.0799 mL | 0.3997 mL | 0.7993 mL | 1.9983 mL | |
| 20 mM | 0.0599 mL | 0.2997 mL | 0.5995 mL | 1.4987 mL | |
| 25 mM | 0.0480 mL | 0.2398 mL | 0.4796 mL | 1.1990 mL | |
| 30 mM | 0.0400 mL | 0.1998 mL | 0.3997 mL | 0.9992 mL | |
| 40 mM | 0.0300 mL | 0.1499 mL | 0.2997 mL | 0.7494 mL | |
| 50 mM | 0.0240 mL | 0.1199 mL | 0.2398 mL | 0.5995 mL | |
| 60 mM | 0.0200 mL | 0.0999 mL | 0.1998 mL | 0.4996 mL | |
| 80 mM | 0.0150 mL | 0.0749 mL | 0.1499 mL | 0.3747 mL | |
| 100 mM | 0.0120 mL | 0.0599 mL | 0.1199 mL | 0.2997 mL |
BCL-XL-IN-3 Related Classifications
HY-170406 Related Classifications
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