Art. -Nr.: HY-157231A

HC-5404-Fu

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HC-5404-Fu is an orally active PERK inhibitor with an IC₅₀ of 0.001 μM against human PERK. HC-5404-Fu blocks PERK activation induced by VEGFR-TKI and disrupts the adaptive stress response triggered by VEGFR-TKI. HC-5404-Fu enhances anti-angiogenic effects by inhibiting newly formed and mature tumor blood vessels in renal cell carcinoma models. HC-5404-Fu can be used in research related to renal cell carcinoma.

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Reinheit: 98.92%
CAS. Nr.: 3034479-99-4
Formel: C₂₄H₂₄F₂N₄O₃.1/2C₄H₄O₄
Molecular Weight:512.51

Speicherung:

4°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)

HC-5404-Fu Chemical Structure

CAS. Nr.: 3034479-99-4

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

Biologische Aktivität

Beschreibung

In Vitro

HC-5404-Fu (1 nM) potently and selectively inhibits recombinant PERK kinase activity in a cell-free biochemical assay with an IC₅₀ of 1 nM, exhibiting >2,000-fold selectivity over other ISR kinases^[1].
HC-5404-Fu (100-10,000 nM) demonstrates high kinome selectivity in a cell-free binding assay, with no off-target kinase interactions at 100 nM and only limited interactions at concentrations ≥1,000 nM^[1].
HC-5404-Fu (1.5 nM-10 μM; 30-minute pretreatment, 4-hour co-incubation with tunicamycin) inhibits ER stress-mediated PERK activation and downstream ATF4 induction in HEK-293 cells with IC₅₀ values of 23 nM (pPERK) and 88 nM (ATF4)^[1].

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

Western Blot Analysis^[1]

Cell Line:

HEK-293 cells
Concentration:

1.5 nM-10 μM
Incubation Time:

30-minute pretreatment; 4-hour co-incubation with tunicamycin
Result:

Inhibited tunicamycin-induced PERK autophosphorylation (pPERK Thr982) with an IC₅₀ of 23 nmol/L.
Inhibited tunicamycin-induced ATF4 protein accumulation with an IC₅₀ of 88 nmol/L.

In Vivo

HC-5404-Fu (3-100 mg/kg; p.o.; single dose) administered as a single oral dose induces rapid, dose-dependent inhibition of pPERK in mouse pancreas and tumor tissue, with 30 mg/kg achieving 90% pPERK inhibition in 786-O tumors at 1 hour^[1].
HC-5404-Fu (3-30 mg/kg; p.o.; twice-a-day; 28 days) administered orally twice-a-day exerts dose-dependent single-agent antitumor activity in 786-O RCC xenografts, with 30 mg/kg twice-a-day achieving 48% TGI^[1].
HC-5404-Fu (30-100 mg/kg; p.o.; twice-a-day; 48 days) administered orally twice-a-day exerts single-agent antitumor activity in Capan-2 pancreatic cancer xenografts, with 30 mg/kg twice-a-day achieving 50% TGI, a comparable effect to the higher 100 mg/kg twice-a-day dose^[1].
HC-5404-Fu (30 mg/kg; p.o.; twice-a-day; 28 days) administered at 30 mg/kg orally twice-a-day enhances the antitumor efficacy of multiple VEGFR-TKI in 786-O RCC xenografts, inhibiting VEGFR-TKI-induced PERK activation and driving tumor regression when combined with axitinib or cabozantinib^[1].
HC-5404-Fu (30 mg/kg; p.o.; twice-a-day; 28 to 30 days) administered at 30 mg/kg orally twice-a-day enhances the antitumor efficacy of sunitinib in both VHL-mutant (A-498) and VHL-wildtype (Caki-1) RCC xenografts, driving 22% tumor regression in A-498 models and 47% TGI in Caki-1 models^[1].
HC-5404-Fu (30 mg/kg; p.o.; twice-a-day; 28 days) administered at 30 mg/kg orally twice-a-day enhances the antitumor efficacy of axitinib across a panel of 18 RCC PDX models, increasing the number of partial responses from 2 to 9 models, with 3 of 6 VHL-wildtype models showing improved response to the combination^[1].
HC-5404-Fu (30 mg/kg; p.o.; twice-a-day; 28 days) administered at 30 mg/kg orally twice-a-day enhances the antitumor efficacy of the anti-VEGFR-2 antibody DC-101 in 786-O and A-498 RCC xenografts, achieving 82% and 78% TGI, respectively^[1].
HC-5404-Fu (30 mg/kg; p.o.; twice-a-day; 28 days) administered at 30 mg/kg orally twice-a-day induces tumor regression (20% relative to baseline) when combined with axitinib in 786-O RCC xenografts that have progressed on axitinib monotherapy, while single-agent HC-5404 achieves 47% tumor growth inhibition relative to vehicle^[1].

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

Animal Model:

athymic nude-Foxn1nu (6- to 8-week-old female; subcutaneously injected with 1×10⁶ T-HEP3-PERK PERK-overexpressing human squamous cell carcinoma cells)^[1]
Dosage:

3 mg/kg; 30 mg/kg; 100 mg/kg
Administration:

p.o.; single dose
Result:

Induced 90% inhibition of pPERK in mouse pancreas at early timepoints post-dosing, with pPERK returning to basal levels by 12 hours (30 mg/kg single oral dose).
Maintained near-complete pPERK inhibition (>80% inhibition) in mouse pancreas for the first 12 hours post-dosing (100 mg/kg single oral dose).
Induced 90% pPERK inhibition in 786-O tumors at 1 hour, which returned to baseline by 8 hours (30 mg/kg single oral dose).

Animal Model:

BALB/c nude (6- to 8-week-old female; subcutaneously injected with 5×10⁶ 786-O RCC cells)^[1]
Dosage:

3 mg/kg; 10 mg/kg; 30 mg/kg
Administration:

p.o.; twice-a-day; 28 days
Result:

Induced the greatest single-agent antitumor effect, resulting in 48% tumor growth inhibition (TGI) (30 mg/kg twice-a-day).

Animal Model:

BALB/c nude (6- to 8-week-old female; subcutaneously injected with 5×10⁶ 786-O RCC cells)^[1]
Dosage:

30 mg/kg
Administration:

p.o.; twice-a-day; 28 days
Result:

Inhibited VEGFR-TKI-induced pPERK accumulation in 786-O tumors.
Resulted in tumor regression relative to baseline when combined with axitinib or cabozantinib.
Enhanced the level of TGI beyond that of either monotherapy when combined with lenvatinib or sunitinib.
Induced a dose-dependent accumulation of ATF4 downstream targets (ASNS, CBS, CTH) in 786-O tumors treated with sunitinib.

Animal Model:

NMRI nu/nu (Crl:NMRI-Foxn1nu; 4- to 6-week-old female; subcutaneously implanted with fragments from 18 RCC patient-derived xenograft (PDX) tumors)^[1]
Dosage:

30 mg/kg
Administration:

p.o.; twice-a-day; 28 days
Result:

Resulted in 9 out of 18 PDX models achieving ≥50% tumor regression from baseline (partial responses) when combined with axitinib, compared with 2 out of 18 partial responses with axitinib monotherapy.
Led to 3 of 6 VHL-wildtype PDX models showing improved response to the combination treatment over axitinib monotherapy, with 2 achieving partial responses, 1 achieving 53% regression (partial response), 2 having stable disease, and 2 having progressive disease (with greater response to combination than monotherapies).

Animal Model:

BALB/c nude (6- to 8-week-old female; subcutaneously injected with 5×10⁶ 786-O RCC cells, 5×10⁶ A-498 RCC cells, or 6×10⁶ Caki-1 RCC cells); NOD.SCID (6- to 8-week-old female; subcutaneously injected with 5×10⁶ 786-O RCC cells, 5×10⁶ A-498 RCC cells, or 6×10⁶ Caki-1 RCC cells)^[1]
Dosage:

30 mg/kg
Administration:

p.o.; twice-a-day; 28 days
Result:

Resulted in 82% TGI in 786-O xenografts when combined with DC-101, improving the effects of each monotherapy.
Resulted in 78% TGI in A-498 xenografts when combined with DC-101, improving the effects of each monotherapy.
Induced only 24% TGI in Caki-1 xenografts when combined with DC-101, with no significant combination benefit observed.

Animal Model:

BALB/c nude (6- to 8-week-old female; subcutaneously injected with 5×10⁶ 786-O RCC cells; tumors progressed on axitinib monotherapy for 14 days)^[1]
Dosage:

30 mg/kg
Administration:

p.o.; twice-a-day; 28 days
Result:

Inhibited tumor growth by 47% relative to vehicle as single-agent.
Resulted in an average 20% tumor regression relative to baseline when combined with axitinib.
Reduced the proportion of Meca32⁺ endothelial cells, CD31⁺SMA⁺ mature blood vessels, and NG2⁺/MCAM⁺ pericytes in tumor sections beyond the effects of axitinib monotherapy when combined with axitinib.

Chemical Information

CAS. Nr. 3034479-99-4
Appearance Solid
Molecular Weight 512.51
Formel C₂₄H₂₄F₂N₄O₃.1/2C₄H₄O₄
Color White to off-white
SMILES

CC(C)NC(C1=CC(C2=CC=C(C=C2C)NC([C@@H](C3=CC(F)=CC(F)=C3)O)=O)=CN=C1N)=O.O=C(O)/C=C/C(O)=O.[1/2]
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

4°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)

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 100 mg/mL (195.12 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

1.9512 mL

9.7559 mL

19.5118 mL

5 mM

0.3902 mL

1.9512 mL

3.9024 mL

10 mM

0.1951 mL

0.9756 mL

1.9512 mL

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.

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 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 5 mg/mL (9.76 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.

Protocol 2

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

Solubility: ≥ 5 mg/mL (9.76 mM); Clear solution

This protocol yields a clear solution of ≥ 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 (50.0 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 (284 KB)
SDS (252 KB)
- English - EN (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)
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]. Stokes ME, et al. PERK Inhibition by HC-5404 Sensitizes Renal Cell Carcinoma Tumor Models to Antiangiogenic Tyrosine Kinase Inhibitors. Clin Cancer Res. 2023;29(23):4870-4882. [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	1.9512 mL	9.7559 mL	19.5118 mL	48.7795 mL
	5 mM	0.3902 mL	1.9512 mL	3.9024 mL	9.7559 mL
	10 mM	0.1951 mL	0.9756 mL	1.9512 mL	4.8780 mL
	15 mM	0.1301 mL	0.6504 mL	1.3008 mL	3.2520 mL
	20 mM	0.0976 mL	0.4878 mL	0.9756 mL	2.4390 mL
	25 mM	0.0780 mL	0.3902 mL	0.7805 mL	1.9512 mL
	30 mM	0.0650 mL	0.3252 mL	0.6504 mL	1.6260 mL
	40 mM	0.0488 mL	0.2439 mL	0.4878 mL	1.2195 mL
	50 mM	0.0390 mL	0.1951 mL	0.3902 mL	0.9756 mL
	60 mM	0.0325 mL	0.1626 mL	0.3252 mL	0.8130 mL
	80 mM	0.0244 mL	0.1219 mL	0.2439 mL	0.6097 mL
	100 mM	0.0195 mL	0.0976 mL	0.1951 mL	0.4878 mL

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HC-5404-Fu

Cell Cycle/DNA Damage Compound Library

Kinase Inhibitor Library

Anti-Cancer Compound Library

Clinical Compound Library

Anti-Aging Compound Library

Endoplasmic Reticulum Stress Compound Library

Orally Active Compound Library

Anti-Pancreatic Cancer Compound Library

Bioactive Compound Library Max

Clinical Compound Library Plus

Bioactive Compound Library

High-Throughput Bioactive Compound Library

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

HC-5404-Fu

Cell Cycle/DNA Damage Compound Library

Kinase Inhibitor Library

Anti-Cancer Compound Library

Clinical Compound Library

Anti-Aging Compound Library

Endoplasmic Reticulum Stress Compound Library

Orally Active Compound Library

Anti-Pancreatic Cancer Compound Library

Bioactive Compound Library Max

Clinical Compound Library Plus

Bioactive Compound Library

High-Throughput Bioactive Compound Library

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

HC-5404-Fu Related Classifications

HY-157231A Related Classifications