2. JAK/STAT Signaling Apoptosis Epigenetics Cell Cycle/DNA Damage NF-κB
  3. Pim Caspase Apoptosis Necroptosis PARP NF-κB
  4. JP-11646

JP-11646 is a pan-PIM inhibitor with increased potency against PIM2 (IC50 = 0.5 nM). JP11646 is freely reversible and ATP non-competitive. JP-11646 results in a decrease of PIM1, 2, and 3 mRNA. JP-11646 can effectively inhibit cell viability in small cell lung cancer (SCLC) and large cell neuroendocrine carcinomas of the lung (LCNEC). JP-11646 can cause a decrease in p-4EBP-1 protein, increasing the cleavage of caspases while decreasing caspase-3. JP-11646 induces apoptosis or necroptosis in cells. JP-11646 leads to reductions in MYC paralogs. JP-11646 can be used for the study of SCLC, LCNEC, human acute leukemia (AML), multiple myeloma (MM), and triple-negative breast cancer (TNBC).

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JP-11646

JP-11646 Chemical Structure

CAS No. : 1902983-63-4

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JP-11646 Related Antibodies

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NF-κB NF-κB1/p50 RelA/p65 RelB c-Rel

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  • Purity & Documentation

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Description

JP-11646 is a pan-PIM inhibitor with increased potency against PIM2 (IC50 = 0.5 nM). JP11646 is freely reversible and ATP non-competitive. JP-11646 results in a decrease of PIM1, 2, and 3 mRNA. JP-11646 can effectively inhibit cell viability in small cell lung cancer (SCLC) and large cell neuroendocrine carcinomas of the lung (LCNEC). JP-11646 can cause a decrease in p-4EBP-1 protein, increasing the cleavage of caspases while decreasing caspase-3. JP-11646 induces apoptosis or necroptosis in cells. JP-11646 leads to reductions in MYC paralogs. JP-11646 can be used for the study of SCLC, LCNEC, human acute leukemia (AML), multiple myeloma (MM), and triple-negative breast cancer (TNBC)[1][2][3][4][5].

IC50 & Target[1][2][3][4][5]

NF-κB

 

Caspase 3

 

PIM2

0.5 nM (IC50)

In Vitro

JP11646 (0.005 to 10 μM, 72 h) inhibits the proliferation of all tested cancer cell lines in a concentration-dependent manner, including head and neck cancer FaDu, ovarian cancer SK-OV-3, breast cancer MDA-MB-231 and BT549, prostate cancer PC-3, liver cancer HepG2, PDAC MIAPaCa-2 and PANC1, colorectal cancer DLD-1 and HT29, and NSCLC H1650, H661, H460 and A549 cell lines[3].
JP11646 (100-200 nM, 24 h) selectively downregulates the protein expression level of PIM2, but has no effect on PIM1 and PIM3, and induces the expression of the apoptosis marker cleaved PARP in MDA-MB-231 and BT549 cells[3].
JP11646 (100-200 nM, 48 h) significantly increases the apoptosis rate of MDA-MB-231 and BT549 cells[3].
JP11646 (20-200 nM, 0-24 h) gradually reduces the levels of p4EBP1 (S65) and pBAD (S112) in MM1.S and U266 cells over time, as do the total levels of these proteins. Furthermore, the levels of the potent phosphorylates form of the anti-apoptotic factor MCL1 (Ser159/Thr163) decrease in a dose-dependent manner[4].
JP11646 (0-1 μM, 72 h) shows the strongest antiproliferative effect against the MF characteristic cell line MM1.S (GI50 = 5 nM)[4].
JP11646 (20-200 nM, 24 h) can reverse (recombinant IL-6) rIL-6-induced PIM2 upregulation in MM1.S and U266 cells, while IL-6 does not affect PIM2 mRNA levels[4].
JP11646 (10-20 nM, 48 h) reverses the chemoprotective effect mediated by CD28 activation or DC co-culture; CTLA4-Ig enhances the cytotoxicity of JP11646[4].
JP11646 (20-200 nM, 0-24 h) dose- and time-dependently inhibits CD28-induced NF-κB activity in MM1.S and RPMI8226 cells[4].

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

JP-11646 Related Antibodies

Western Blot Analysis[3]

Cell Line: MDA-MB-231 cells, BT549 cells
Concentration: 100 nM, 200 nM
Incubation Time: 24 h
Result: Downregulated the protein expression level of PIM2, but had no effect on PIM1 and PIM3, and induced the expression of the apoptosis marker cleaved PARP in MDA-MB-231 and BT549 cells.

Apoptosis Analysis[3]

Cell Line: MDA-MB-231 cells, BT549 cells
Concentration: 100 nM, 200 nM
Incubation Time: 48 h
Result: Significantly increased the apoptosis rate of MDA-MB-231 and BT549 cells.
In Vivo

JP11646 (15 mg/kg, i.p., twice every week, 24-40 days) demonstrates broad-spectrum and potent antitumor activity in various mouse xenograft tumor in vivo models, with no significant toxic effects observed[3].
JP11646 (10-15 mg/kg, i.p., 2 or 3 times a week for 48 days) demonstrates potent dose-dependent antitumor activity in a mice model of multiple myeloma xenograft and significantly prolongs the median survival of tumor-bearing mice[4].

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

Animal Model: Cell suspensions (1×106 of MDA‑MB‑231, 3×106 of MIAPaCa‑2, 2×106 of PANC‑1, 5×106 of HepG2, 5×106 of A549, 5×106 of HT29 and 5×106 of H1650) in a mixture of 50 µl PBS and 50 µl Matrigel were injected subcutaneously into the CB17 SCID mice (female, 6‑8 weeks‑old, weighing 18‑22 g) flanks, or in the case of MDA‑MB‑231 cells, into the abdomen mammary fat pads[3].
Dosage: 15 mg/kg
Administration: I.p., twice every week (MDA‑MB‑231, 24 days; HepG2, 23 days; MIAPaCa‑2, 29 days; PANC‑1, 40 days; A549, 29 days; H1650, 18 days; HT29, 12 days)
Result: Demonstrated significant tumor growth inhibition in five models: MDA-MB-231 (breast cancer), HepG2 (liver cancer), MIAPaCa-2 (pancreatic cancer), A549 (lung cancer), and H1650 (lung cancer).
Did not show significant efficacy in two models (PANC-1 pancreatic cancer and HT29 colorectal cancer).
No mice experienced weight loss exceeding 20% or other detectable serious side effects.
Animal Model: SCID/SCIDCBIgh.lblcrTac.Prkdcscid/Ros mice < 5 weeks of age were irradiated at 300 rads using a Mark II Cesium irradiator 24 hours before injecting them with MM1.S cells (5×106) subcutaneously under the skin on the left ventral flank[4].
Dosage: 10 mg/kg, 15 mg/kg
Administration: I.p., 2 or 3 times a week for 48 days
Result: The relative tumor volume in the 10 mg/kg and 15 mg/kg groups was reduced to 49% and 89% of that in the control group, respectively.
The 15 mg/kg group showed a tumor reduction of over 91%.
The median survival in the 10 mg/kg group was prolonged to 27 days.
The median survival in the 15 mg/kg group was significantly prolonged to 48 days.
During the two-week observation period after treatment cessation in the 15 mg/kg group, two of the three surviving mice did not show tumor regeneration.
Molecular Weight

459.56

Formula

C25H25N5O2S
CAS No.
Appearance

Solid

Color

Light yellow to yellow

SMILES

O=C1NC(/C(S1)=C/C2=CC=NC(N[C@H]3CC[C@@H](CC3)NCC4=CC=CC5=C4C=CC=C5)=N2)=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

4°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

Solvent & Solubility
In Vitro: 

DMSO : 100 mg/mL (217.60 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 2.1760 mL 10.8800 mL 21.7599 mL
5 mM 0.4352 mL 2.1760 mL 4.3520 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 (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

  • Dilution Calculator

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

Mass
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Concentration
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Volume
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Molecular Weight *

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

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

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Volume (start)

V1

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Concentration (final)

C2

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Volume (final)

V2

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 (5.44 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 (5.44 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:

Dosage

mg/kg

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(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
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 (protect from light)

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 (protect from 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 2.1760 mL 10.8800 mL 21.7599 mL 54.3999 mL
5 mM 0.4352 mL 2.1760 mL 4.3520 mL 10.8800 mL
10 mM 0.2176 mL 1.0880 mL 2.1760 mL 5.4400 mL
15 mM 0.1451 mL 0.7253 mL 1.4507 mL 3.6267 mL
20 mM 0.1088 mL 0.5440 mL 1.0880 mL 2.7200 mL
25 mM 0.0870 mL 0.4352 mL 0.8704 mL 2.1760 mL
30 mM 0.0725 mL 0.3627 mL 0.7253 mL 1.8133 mL
40 mM 0.0544 mL 0.2720 mL 0.5440 mL 1.3600 mL
50 mM 0.0435 mL 0.2176 mL 0.4352 mL 1.0880 mL
60 mM 0.0363 mL 0.1813 mL 0.3627 mL 0.9067 mL
80 mM 0.0272 mL 0.1360 mL 0.2720 mL 0.6800 mL
100 mM 0.0218 mL 0.1088 mL 0.2176 mL 0.5440 mL
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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:

JP-116461902983-63-4JP11646JP 11646PimCaspaseApoptosisNecroptosisPARPNF-κBPim kinasespoly ADP ribose polymerase Nuclear factor-κBNuclear factor-kappaBSmall Cell Lung Cancerlarge cell neuroendocrine carcinomas of the lungPIM2MYCp-4EBP-1caspase-3human acute leukemiaAMLtriple-negative breast cancer (TNBC)Inhibitorinhibitorinhibit

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