Art. -Nr.: HY-143286

PF15

PF15 is an orally active FLT3-ITD PROTAC degrader with a DC₅₀ of 76.7 nM and an IC₅₀ of 36 nM against FLT3-ITD. PF15 induces FLT3-ITD protein degradation, thereby downregulating its phosphorylation level. PF15 inhibits the proliferation of FLT3-ITD-positive cells and reduces the phosphorylation level of STAT5, a downstream molecule of FLT3-ITD. PF15 exhibits efficacy in in vivo xenograft models of acute myeloid leukemia and prolongs survival. PF15 can be used for the research of acute myeloid leukemia.
(Pink: FLT3 Target protein ligand; Blue: Cereblon ligand (HY-A0003); Black: linker).

Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.

CAS. Nr.: 2892631-70-6
Formel: C₄₄H₄₉N₁₃O₆
Molecular Weight:855.94

Speicherung:

Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (287 KB)

PF15 Chemical Structure

CAS. Nr.: 2892631-70-6

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Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

PF15 is an orally active FLT3-ITD PROTAC degrader with a DC₅₀ of 76.7 nM and an IC₅₀ of 36 nM against FLT3-ITD. PF15 induces FLT3-ITD protein degradation, thereby downregulating its phosphorylation level. PF15 inhibits the proliferation of FLT3-ITD-positive cells and reduces the phosphorylation level of STAT5, a downstream molecule of FLT3-ITD. PF15 exhibits efficacy in in vivo xenograft models of acute myeloid leukemia and prolongs survival. PF15 can be used for the research of acute myeloid leukemia^[1]. (Pink: FLT3 Target protein ligand; Blue: Cereblon ligand (HY-A0003); Black: linker).

IC₅₀ & Target^[1]

STAT5

Alle PROTACs Isoform-spezifische Produkte anzeigen :

Alle STAT Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
MV4-11	IC₅₀	4.83 nM Compound: 6; PF15	Antiproliferative activity against human MV4-11 cells assessed as reduction in cell viability measured after 48 hrs by CellTiter-Glo assay Antiproliferative activity against human MV4-11 cells assessed as reduction in cell viability measured after 48 hrs by CellTiter-Glo assay	[PMID: 39094274]

In Vitro

PF15 potently and selectively inhibits FLT3 kinase with an IC₅₀ of 36 nM, and its inhibitory potency against c-Kit kinase is over 35-fold lower; it exhibits high selectivity for FLT3 among a panel of 93 tumor-related kinases^[1].
PF15 (1-2000 nM; 1-24 h) induces proteasome-dependent degradation of FLT3 protein in BaF3-FLT3-ITD cells, with a DC₅₀ of 76.7 nM, and prolonged incubation achieves complete degradation of the protein^[1].
PF15 (10-1000 nM; 2 h) upregulates FLT3 mRNA levels in BaF3-FLT3-ITD cells at low concentrations (10 nM, 30 nM)^[1].
PF15 (72 h) potently inhibits the proliferation of MV4-11 FLT3-ITD-positive AML cells with an IC₅₀ of 4.83 nM; potently inhibits the proliferation of Molm-13 FLT3-ITD-positive AML cells with an IC₅₀ of 4.01 nM; potently inhibits the proliferation of BaF3-FLT3-ITD transformed cells with an IC₅₀ of 7.85 nM; inhibits the proliferation of drug-resistant BaF3-FLT3-ITD-D835V transformed cells with an IC₅₀ of 120.1 nM; inhibits the proliferation of drug-resistant BaF3-FLT3-ITD-F691L transformed cells with an IC₅₀ of 116.6 nM; and exhibits only extremely low antiproliferative activity against FLT3 wild-type cancer cells (THP-1, K562, Daudi, HEL, Jurkat, RS4;11)^[1].
PF15 (10-1000 nM; 6 h) downregulates the phosphorylation levels of FLT3 and STAT5 in BaF3-FLT3-ITD, BaF3-FLT3-ITD-D835V, and BaF3-FLT3-ITD-F691L cells at a concentration of 100 nM after 6 h of treatment, whereas a higher concentration is required for FLT3 degradation^[1].

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

Cell Proliferation Assay^[1]

Cell Line:

FLT3 wild-type cancer cells (THP-1, K562, Daudi, HEL, Jurkat, RS4;11)
Concentration:

40 μM
Incubation Time:

72 h
Result:

Hardly inhibited proliferation of all tested FLT3 wild-type cell lines even at the maximum tested concentration of 40 μM.

Western Blot Analysis^[1]

Cell Line:

BaF3-FLT3-ITD cells
Concentration:

1, 3, 10, 30, 100, 300, 1000 nM (6 h incubation)
100 nM
15.6, 31.2, 62.5, 250, 500, 1000, 2000 nM (24 h incubation)
1000 nM (6 h incubation, with 1 h MG132 (HY-13259) pre-treatment)
Incubation Time:

6 h
1, 3, 6, 12, 24 h
24 h
6 h (with 1 h MG132 pre-treatment)
Result:

Induced dose-dependent FLT3 degradation with a DC₅₀ of 76.7 nM after 24 h of treatment, and achieves complete degradation with extended incubation.
Achieved complete degradation after 24 h of treatment at sufficient concentrations.
Pre-treatment with proteasome inhibitor MG132 completely blocked PF15-induced FLT3 degradation.

Western Blot Analysis^[1]

Cell Line:

BaF3-FLT3-ITD cells
Concentration:

10, 30, 100, 300, 1000 nM
Incubation Time:

6 h
Result:

Dramatically inhibited phosphorylation of FLT3 and STAT5 in a dose-dependent manner.
Downregulated p-FLT3 more pronouncedly than p-STAT5.

Western Blot Analysis^[1]

Cell Line:

BaF3-FLT3-ITD-D835V cells
Concentration:

10, 30, 100, 300, 1000 nM
Incubation Time:

6 h
Result:

Sharply downregulated phosphorylation of FLT3 and STAT5 at 100 nM.
Required high concentrations to induce FLT3 protein degradation.

Western Blot Analysis^[1]

Cell Line:

BaF3-FLT3-ITD-F691L cells
Concentration:

10, 30, 100, 300, 1000 nM
Incubation Time:

6 h
Result:

Sharply downregulated phosphorylation of FLT3 and STAT5 at 100 nM.
Required high concentrations to induce FLT3 protein degradation.

In Vivo

PF15 (10-20 mg/kg; i.p.; daily; 10 days) inhibits AML tumor growth in a subcutaneous xenograft model, with the 10 mg/kg daily i.p. dose achieving 58.4% tumor growth inhibition and no observable organ toxicity^[1].
PF15 (20-40 mg/kg; p.o.; twice daily; 12 days; i.p.; daily; 12 days) significantly extends survival in an AML in situ xenograft model, with the 20 mg/kg twice-daily p.o. dose increasing median survival from 11 days to 15 days^[1].

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

Animal Model:

NOD/SCID (female; subcutaneous xenograft model via implantation of 10⁷ BaF3-FLT3-ITD cells)^[1]
Dosage:

10 mg/kg; 20 mg/kg
Administration:

i.p.; daily; 10 days
Result:

Achieved a tumor growth inhibition rate of 58.4% at 10 mg/kg.
Achieved a higher tumor growth inhibition rate at 20 mg/kg.
Showed no significant changes in serum AST, urea, and CK-MB levels at both doses.

Animal Model:

BALB/c nude (female; in situ xenograft model via tail vein injection of 1×10⁶ BaF3-FLT3-ITD cells)^[1]
Dosage:

20 mg/kg; 40 mg/kg
Administration:

p.o.; twice daily; 12 days; i.p.; daily; 12 days
Result:

Prolonged median survival to 15 days at 20 mg/kg twice-daily dose.
Resulted in median survival equivalent to the 20 mg/kg twice-daily dose at 40 mg/kg daily dose.

Chemical Information

CAS. Nr. 2892631-70-6
Molecular Weight 855.94
Formel C₄₄H₄₉N₁₃O₆
SMILES

CC(C)(C1=CC(NC(NC2=CC=C(C=C2)C3=CN(C4=NC=NC(N)=C34)CCCCC5=CN(N=N5)CCCCC(NC6=C7CN(C(C7=CC=C6)=O)C8CCC(NC8=O)=O)=O)=O)=NO1)C
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

Please store the product under the recommended conditions in the Certificate of Analysis.

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 100 mg/mL (116.83 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.1683 mL

5.8415 mL

11.6831 mL

5 mM

0.2337 mL

1.1683 mL

2.3366 mL

10 mM

0.1168 mL

0.5842 mL

1.1683 mL

Molaritätsrechner

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

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

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 (2.92 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.

Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (2.92 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
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

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (287 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Chen Y, et al. Degrading FLT3-ITD protein by proteolysis targeting chimera (PROTAC). Bioorganic chemistry. 2022 Feb;119:105508. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	1.1683 mL	5.8415 mL	11.6831 mL	29.2077 mL
	5 mM	0.2337 mL	1.1683 mL	2.3366 mL	5.8415 mL
	10 mM	0.1168 mL	0.5842 mL	1.1683 mL	2.9208 mL
	15 mM	0.0779 mL	0.3894 mL	0.7789 mL	1.9472 mL
	20 mM	0.0584 mL	0.2921 mL	0.5842 mL	1.4604 mL
	25 mM	0.0467 mL	0.2337 mL	0.4673 mL	1.1683 mL
	30 mM	0.0389 mL	0.1947 mL	0.3894 mL	0.9736 mL
	40 mM	0.0292 mL	0.1460 mL	0.2921 mL	0.7302 mL
	50 mM	0.0234 mL	0.1168 mL	0.2337 mL	0.5842 mL
	60 mM	0.0195 mL	0.0974 mL	0.1947 mL	0.4868 mL
	80 mM	0.0146 mL	0.0730 mL	0.1460 mL	0.3651 mL
	100 mM	0.0117 mL	0.0584 mL	0.1168 mL	0.2921 mL

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PF15

Alle PROTACs Isoform-spezifische Produkte anzeigen

Alle STAT Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

PF15 Related Classifications

HY-143286 Related Classifications