HPK1-IN-32 |
Katalog-Nr.GC69240
One-Click Copy Product Info
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HPK1-IN-32 ist ein wirksamer selektiver HPK1-Inhibitor mit einer IC50 von 65 nM. HPK1-IN-32 kann für die Erforschung von HPK1-bezogenen Krankheiten verwendet werden.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2766481-17-6
Sample solution is provided at 25 µL, 10mM.
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HPK1-IN-32 is a highly selective, orally active small-molecule inhibitor of hematopoietic progenitor kinase 1 (HPK1/MAP4K1) with an IC50 of 1.04nM. HPK1-IN-32 activates ERK phosphorylation, enhances T cell activation and proliferation, and increases the secretion of effector cytokines such as IL-2 and IFN-γ. HPK1-IN-32 can be used for cancer immunotherapy of advanced solid tumors and related immuno-oncology research[1-2].
In vitro, HPK1-IN-32 (0.25μM–15μM) was applied to human acute myeloid leukemia cell lines (MV4-11, MOLM-13, THP-1, U937, KG1, KG1A, etc.) for 48–72 hours. HPK1-IN-32 reduced HPK1 expression in these cells, inhibited AML cell proliferation, decreased viable cell numbers, induced apoptosis, and promoted G0/G1 phase arrest[3]. HPK1-IN-32 (0–2μM) was applied to Jurkat T cells and human peripheral blood mononuclear cells for 2 hours. HPK1-IN-32 inhibited HPK1 kinase activity and downstream SLP76 phosphorylation at Ser376, enhanced TCR signaling pathway transduction, and promoted the production of cytokines such as IL-2 and IFN-γ[4].
In vivo, HPK1-IN-32 (25–50mg/kg/day; every other day) was intraperitoneally injected into NCG mice engrafted with AML cells for 14 consecutive days. HPK1-IN-32 reduced leukemia burden and prolonged animal survival without causing body weight loss in mice[3]. HPK1-IN-32 (2mg/kg; single injection) was administered via tail vein to C57BL/6J mice subjected to 90-minute middle cerebral artery occlusion followed by reperfusion, given 30 minutes after reperfusion. HPK1-IN-32 alleviated pulmonary alveolar septal thickening and leukocyte infiltration, reduced total protein concentration in bronchoalveolar lavage fluid, inhibited neutrophil infiltration into the lungs and ischemic brain tissue as well as citrullinated histone H3 (CitH3)-labeled neutrophil extracellular trap (NET) formation, decreased cerebral infarct volume, improved modified neurological severity score (mNSS), and suppressed the upregulation of microglial CD86 in the brain[5].
References:
[1] Liu Y, Li J, Li Z, et al. Abstract 5541: BGB-15025, a potent and selective HPK1 inhibitor, is efficacious as a single agent or in combination with PD-1 antibody in multiple tumor models. Cancer Res 2022; 82(Suppl 12):5541–5541.
[2] Deva S, Zhou C, Bishnoi SK, et al. A first-in-human phase 1a dose-escalation study of BGB-15025 (HPK1 inhibitor) as monotherapy and in combination with tislelizumab (TIS; anti-PD-1 antibody) in patients (pts) with advanced solid tumors. J Clin Oncol 2024; 42:2585–2585.
[3] Yang S, Li F, Zhuang H, et al. Hematopoietic progenitor kinase 1 inhibitor BGB-15025 induces apoptosis in acute myeloid leukemia cells through the cell cycle pathway and mitogen-activated protein kinase/extracellular signal-regulated kinase pathway signaling axis. Anticancer Drugs. 2026 Jun 1;37(5):329-342.
[4] Sanjia XU, Jing Li, Zhiwei Wang, et al. 3-[(1h-pyrazol-4-yl)oxy]pyrazin-2-amine compounds as hpk1 inhibitor and use thereof. Patent. WO2022068848.
[5] Zhang T, Sun Y, Xia J, et al. Targeting HPK1 inhibits neutrophil responses to mitigate post-stroke lung and cerebral injuries. EMBO Mol Med. 2025 May;17(5):1018-1040.
| Cell experiment [1]: | |
Cell lines | MV4-11 (FLT3-ITD), MOLM-13 (MLL-rearranged), U937 (TP53mut), THP-1 (DNMT3A/ASXL1mut), KG1 (BCR-ABL1neg), and KG1A (BCR-ABL1pos) human acute myeloid leukemia cell lines, as well as primary AML blasts isolated from bone marrow aspirates of newly diagnosed patients with AML |
Preparation Method | AML cell lines were cultured in complete RPMI 1640 medium supplemented with 10% fetal bovine serum (FBS) at 37°C with 5% CO₂. Primary AML maintained in culture medium containing 20% FBS. AML cell lines and primary AML cells were seeded in 24-well plates, then exposed to graded concentrations of HPK1-IN-32 and incubated for 48 or 72 hours. |
Reaction Conditions | 0.25μM–15μM; 48–72h |
Applications | HPK1-IN-32 reduced HPK1 mRNA transcript and protein expression in a dose-dependent manner in THP-1 and KG1A cells. HPK1-IN-32 exerted potent cytotoxicity against AML cell lines and primary AML progenitors, significantly inhibiting cell proliferation in a concentration- and time-dependent fashion. HPK1-IN-32 induced apoptosis in AML cells in a concentration-dependent manner and caused G0/G1 phase arrest, as evidenced by an increased proportion of cells in G0/G1 phase and a concomitant decrease in the S-phase population. HPK1-IN-32 downregulated cyclin D1 and CDK4 while upregulating P21 at both transcript and protein levels, and suppressed MAPK/ERK signaling through reduced total MAPK levels and attenuated phosphorylation of ERK and P38 (p-ERK and p-P38). |
| Animal experiment [2]: | |
Animal models | Adult C57BL/6J mice (male, with both sexes additionally used for selected lung/brain endpoint validations) subjected to transient focal cerebral ischemia–reperfusion |
Preparation Method | Mice were anesthetized and underwent middle cerebral artery occlusion (MCAO; 60min for mechanistic tissue/time-course analyses or 90min for therapeutic assessment) via intraluminal silicone-coated filament, followed by reperfusion. HPK1-IN-32 was administered once daily via tail intravenous injection at 30min after reperfusion (MCAO/R), and animals were sacrificed at defined reperfusion time points (24h for neutrophil infiltration/oxidative and microglial activation readouts, 48h for infarct and neurological scoring together with lung histopathology/bronchoalveolar lavage fluid analysis, and 72h for infarct volume, modified neurological severity score, and lung citrullinated histone H3 immunohistochemistry). |
Dosage form | 2mg/kg; i.v.; single dose after 30 minutes of reperfusion |
Applications | HPK1-IN-32 attenuated neutrophil infiltration and citrullinated histone H3 (CitH3)–positive neutrophil extracellular trap formation in the lung and brain, reduced lung alveolar septal thickening and leukocyte infiltration, lowered total protein concentration in bronchoalveolar lavage fluid (reflecting reduced alveolar–capillary barrier disruption), decreased CD86 upregulation on brain microglia, reduced cerebral infarct volume, and improved modified neurological severity score after MCAO/R. |
References: | |
| Cas No. | 2766481-17-6 | SDF | |
| Formula | C28H37FN8O2 | M.Wt | 536.64 |
| Löslichkeit | DMSO : 50 mg/mL (93.17 mM; Need ultrasonic) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8634 mL | 9.3172 mL | 18.6345 mL |
| 5 mM | 372.7 μL | 1.8634 mL | 3.7269 mL |
| 10 mM | 186.3 μL | 931.7 μL | 1.8634 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)