2. Cell Cycle/DNA Damage Metabolic Enzyme/Protease Autophagy
  3. HSP Beclin1 Autophagy
  4. AP-4-139B

AP-4-139B is a blood-brain barrier-permeable HSP70 inhibitor with a IC50 of 180 nM against hHSP70. AP-4-139B binds directly to HSP70 and inhibits its ATPase activity. AP-4-139B promotes Autophagy by increasing the phosphorylation of Beclin-1. AP-4-139B exerts antitumor effects in preclinical models of colorectal cancer and pancreatic ductal adenocarcinoma.

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AP-4-139B

AP-4-139B Chemical Structure

CAS No. : 2716909-84-9

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Based on 1 publication(s) in Google Scholar

AP-4-139B Related Antibodies

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Description

AP-4-139B is a blood-brain barrier-permeable HSP70 inhibitor with a IC50 of 180 nM against hHSP70. AP-4-139B binds directly to HSP70 and inhibits its ATPase activity. AP-4-139B promotes Autophagy by increasing the phosphorylation of Beclin-1. AP-4-139B exerts antitumor effects in preclinical models of colorectal cancer and pancreatic ductal adenocarcinoma[1][2].

IC50 & Target[1]

HSP70

180 nM (IC50)

In Vitro

AP-4-139B potently inhibits the ATPase activity of purified hHSP70, with an IC50 of 180 nM[1].
AP-4-139B (500 nM; 24 h) impairs mitochondrial function (reduced basal OCR and ATP production) in 1205Lu melanoma cells and HT-29 colorectal cancer cells, but exerts no significant effects on IMR90 human fibroblasts or CCD 841 CoN normal colonic epithelial cells[1].
AP-4-139B (48 h) exhibits potent cytotoxicity against colorectal cancer (CRC) cell lines, with an IC50 of 1.5-3 μM[1].
AP-4-139B (1-5 μM; 24 h) induces autophagy in TCC-Pan2, PK-8, MIA PaCa-2 and PANC-1 pancreatic ductal adenocarcinoma (PDAC) cells, which is evidenced by increased phosphorylation level of Beclin-1 and lipidation of LC3B[2].
AP-4-139B (0.19-15 μM; 72 h) acts synergistically with chloroquine, an autophagy inhibitor, to reduce the viability of TCC-Pan2, PK-8, MIA PaCa-2 and PANC-1 pancreatic ductal adenocarcinoma (PDAC) cells[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

AP-4-139B Related Antibodies

Western Blot Analysis[2]

Cell Line: Hs766T, PANC-1, MIA PaCa-2
Concentration: 5 μM (Hs766T, PANC-1); 2.5 μM (MIA PaCa-2)
Incubation Time: 24-72 h (Hs766T, PANC-1); 48-72 h (MIA PaCa-2)
Result: Caused a time-dependent decrease in DRP1 phosphorylation at serine 616 in Hs766T cells, with significant reductions observed at 24, 48, and 72 h compared to untreated cells.
Caused a time-dependent decrease in DRP1 phosphorylation at serine 616 in PANC-1 cells, with significant reductions observed at 24, 48, and 72 h compared to untreated cells.
Caused a time-dependent decrease in DRP1 phosphorylation at serine 616 in MIA PaCa-2 cells, with significant reductions observed at 48 and 72 h compared to untreated cells.

Western Blot Analysis[2]

Cell Line: TCC-Pan2, PK-8, MIA PaCa-2, PANC-1
Concentration: 1-5 μM
Incubation Time: 24 h
Result: Caused a dose-dependent increase in phospho-Beclin-1 (S93) levels and LC3B-II levels in TCC-Pan2 cells compared to untreated cells.
Caused a dose-dependent increase in phospho-Beclin-1 (S93) levels and LC3B-II levels in PK-8 cells compared to untreated cells.
Caused a dose-dependent increase in phospho-Beclin-1 (S93) levels and LC3B-II levels in MIA PaCa-2 cells compared to untreated cells.
Caused a dose-dependent increase in phospho-Beclin-1 (S93) levels and LC3B-II levels in PANC-1 cells compared to untreated cells.
In Vivo

AP-4-139B (12.5 mg/kg; three times per week) significantly inhibits HT-29 colorectal cancer xenograft progression (p<0.001) and induces tumor cell apoptosis without causing systemic toxicity[1].
AP-4-139B (10 mg/kg; every 48 hours) significantly inhibits MC38 colorectal cancer xenograft progression (p<0.001) and promotes immune cell recruitment into tumor tissue without causing systemic toxicity[1].
AP-4-139B (10 mg/kg; i.p.; every other day) significantly reduces PK-8 PDAC xenograft tumor growth in vivo[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) (male, 6-8 week old, subcutaneous injection of 2.5 x 106 HT-29 cells)[1]
Dosage: 12.5 mg/kg
Administration: three times per week
Result: Significantly reduced HT-29 tumor xenograft progression relative to control (p<0.001).
Reduced Ki-67-positive proliferative cells in tumor tissue relative to control.
Reduced staining for HSP70 client proteins NDUFA6 and mutant p53 in tumor tissue relative to control.
Increased staining for cleaved lamin A (apoptosis marker) in tumor tissue relative to control.
Showed no signs of toxicity (weight loss, abnormal liver/colon architecture).
Animal Model: C57Bl/6J (male, 6-8 week old, subcutaneous injection of 1 x 106 MC38 cells)[1]
Dosage: 10 mg/kg
Administration: every 48 hours
Result: Significantly reduced MC38 tumor xenograft progression relative to control (p<0.001).
Increased infiltration of CD8+ T cells, Granzyme B-positive activated T cells, conventional CD4+ T cells, regulatory T cells (Tregs), and dendritic cells in tumor tissue relative to control.
Showed no changes in CD8+ T cells, Granzyme B-positive activated T cells, conventional CD4+ T cells, regulatory T cells (Tregs), and dendritic cell populations in mouse spleens relative to control.
Showed no signs of toxicity (weight loss).
Animal Model: NSG mice (subcutaneous injection of PK-8 cells)[2]
Dosage: 10 mg/kg
Administration: i.p.; every other day
Result: Significantly reduced tumor volume and tumor weight at endpoint compared to vehicle controls.
Caused no significant weight loss.
Molecular Weight

626.59

Formula

C34H33BrN3PS
CAS No.
Appearance

Solid

Color

White to off-white

SMILES

C1([P+](C2=CC=CC=C2)(C3=CC=CC=C3)CCCCCCC4=NN5C=C(N=C5S4)C6=CC=CC=C6)=CC=CC=C1.[Br-]
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

-20°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Solvent & Solubility
In Vitro: 

DMSO : 100 mg/mL (159.59 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.5959 mL 7.9797 mL 15.9594 mL
5 mM 0.3192 mL 1.5959 mL 3.1919 mL
View the 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). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

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In Vivo:

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.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (3.99 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2.5 mg/mL (3.99 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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.
In Vivo Dissolution Calculator
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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Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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).
Calculation results:
Working solution concentration: 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)

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
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
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). 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 1.5959 mL 7.9797 mL 15.9594 mL 39.8985 mL
5 mM 0.3192 mL 1.5959 mL 3.1919 mL 7.9797 mL
10 mM 0.1596 mL 0.7980 mL 1.5959 mL 3.9898 mL
15 mM 0.1064 mL 0.5320 mL 1.0640 mL 2.6599 mL
20 mM 0.0798 mL 0.3990 mL 0.7980 mL 1.9949 mL
25 mM 0.0638 mL 0.3192 mL 0.6384 mL 1.5959 mL
30 mM 0.0532 mL 0.2660 mL 0.5320 mL 1.3299 mL
40 mM 0.0399 mL 0.1995 mL 0.3990 mL 0.9975 mL
50 mM 0.0319 mL 0.1596 mL 0.3192 mL 0.7980 mL
60 mM 0.0266 mL 0.1330 mL 0.2660 mL 0.6650 mL
80 mM 0.0199 mL 0.0997 mL 0.1995 mL 0.4987 mL
100 mM 0.0160 mL 0.0798 mL 0.1596 mL 0.3990 mL
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AP-4-139B Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

AP-4-139B2716909-84-9HSPBeclin1AutophagyHeat shock proteinsAtg6AMPKmitochondrial dynamicsimmunogenic cell deathBeclin-1HSPA1APINK1colorectal cancerepithelial-mesenchymal transitionautophagic fluxpancreatic ductal adenocarcinomaInhibitorinhibitorinhibit

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