| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other sizes |
| Targets |
HPK1 (IC50 = 2.6 nM); GLK/MAP4K3 (IC50 = 140 nM); IRAK4 (IC50 = 59 nM); Fms/CSFR (IC50 = 3.2 nM ); FLT3 (IC50 = 25.4 nM);AMPKA1 (IC50 = 44.3 nM); cKIT (IC50 = 45.7 nM); MST1(IC50 = 55.1 nM)
HPK1-IN-7 targets hematopoietic progenitor kinase 1 (HPK1/MAP4K1), a serine/threonine kinase that negatively regulates T-cell receptor (TCR) signaling. By inhibiting HPK1, the compound enhances T-cell activation and anti-tumor immunity. It also shows selectivity against IRAK4 (59 nM) and GLK (140 nM). The compound's excellent kinome selectivity minimizes off-target effects. |
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| ln Vitro |
In vitro, HPK1-IN-7 potently inhibits HPK1 with an IC50 of 2.6 nM. It demonstrates excellent family and kinome selectivity and shows selectivity against IRAK4 (59 nM) and GLK (140 nM). These activities confirm its role as a highly selective HPK1 inhibitor for modulating T-cell signaling and immune responses.
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| ln Vivo |
In a syngeneic tumor model of colorectal cancer, HPK1-IN-7 (100 mg/kg; p.o.; twice daily for 28 days) exhibits a significant enhancement of anti-PD1 efficacy.
HPK1-IN-7 (compound 24) has a volume of distribution of 4.4 L/kg and a moderate plasma clearance of 43 mL/min/kg. It is administered intravenously to mice at a dose of 1 mg/kg. The AUC0-24h was 19 M•h and the Cmax was 5.3 M following oral administration (20 mg/kg). Based on these pharmacokinetics studies, the calculated oral bioavailability is approximately 100%. In vivo, in a syngeneic tumor model of colorectal cancer, HPK1-IN-7 (100 mg/kg; p.o.; twice daily for 28 days) exhibits a significant enhancement of anti-PD1 efficacy. This demonstrates the compound's potential as an immuno-oncology agent that can synergize with immune checkpoint inhibitors. The compound's oral activity and efficacy in combination with anti-PD1 therapy support its further development for cancer immunotherapy. |
| Enzyme Assay |
The HPK1 inhibitory activity is assessed using kinase activity assays. Recombinant HPK1 enzyme is incubated with a peptide substrate and ATP in the presence of various concentrations of HPK1-IN-7. The phosphorylation of the substrate is measured using a luminescent or fluorescent readout, and IC50 values are calculated from dose-response curves. Selectivity is assessed by profiling the compound against a panel of kinases.
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| Cell Assay |
For cellular studies, T cells or immune cell lines are cultured in appropriate media. Cells are treated with HPK1-IN-7 at various concentrations, and T-cell receptor signaling is assessed by measuring downstream phosphorylation events (e.g., ERK, Akt) or cytokine production (e.g., IL-2, IFN-γ). Cell viability is assessed using standard assays. The compound's effects on T-cell activation and proliferation are evaluated.
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| Animal Protocol |
Animal Model:Mice (MC38 syngeneic tumor model)
Dosage: 100mg/kg Administration: Oral; twice daily for 28 days Result: increased the anti-PD1 treatment's effectiveness, achieving a 100% cure rate as opposed to a 20% cure rate with anti-PD1 alone. In vivo efficacy is evaluated in syngeneic tumor models of colorectal cancer. Tumor-bearing mice are treated with HPK1-IN-7 at 100 mg/kg via oral gavage twice daily for 28 days, alone or in combination with anti-PD1 antibody. Tumor volumes are measured, and immune cell infiltration and activation in the tumor microenvironment are assessed by flow cytometry or immunohistochemistry. The combination with anti-PD1 demonstrates significant enhancement of anti-tumor efficacy. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for HPK1-IN-7 indicate it is orally active. In animal studies, the compound has a volume of distribution of 4.4 L/kg and a moderate plasma clearance of 43 mL/min/kg. These parameters suggest favorable pharmacokinetic properties for oral dosing. Further pharmacokinetic studies would be required to determine additional parameters such as half-life, Cmax, and oral bioavailability.
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| Toxicity/Toxicokinetics |
Specific toxicology data for HPK1-IN-7 are not detailed in the available literature. As an HPK1 inhibitor that enhances T-cell activation, potential immune-related adverse effects would need to be carefully evaluated. Comprehensive toxicology studies including repeated-dose toxicity and safety pharmacology assessments would be required before clinical development. The compound should be handled with appropriate safety precautions.
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| References | |
| Additional Infomation |
HPK1-IN-7 is a potent, orally active HPK1 inhibitor (IC50 = 2.6 nM) with excellent kinome selectivity. It enhances anti-PD1 efficacy in a colorectal cancer syngeneic model at 100 mg/kg twice daily. It is being developed as an immuno-oncology agent. No clinical trials or approvals exist. For research use only.
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| Molecular Formula |
C24H22N6O4
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|---|---|
| Molecular Weight |
458.469284534454
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| Exact Mass |
458.17
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| Elemental Analysis |
C, 62.87; H, 4.84; N, 18.33; O, 13.96
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| CAS # |
2320462-65-3
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| Related CAS # |
2320462-65-3;
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| PubChem CID |
142587219
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| Appearance |
White to off-white solid powder
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| LogP |
2.7
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
34
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| Complexity |
705
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1(C2=C(C=CC(=C2)NC3=NC=C(C(=N3)N[C@H](CO)C4=CC=CC=C4)C5=NN=CO5)C(=O)O1)C
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| InChi Key |
RVSSNRBUPQUIEG-LJQANCHMSA-N
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| InChi Code |
InChI=1S/C24H22N6O4/c1-24(2)18-10-15(8-9-16(18)22(32)34-24)27-23-25-11-17(21-30-26-13-33-21)20(29-23)28-19(12-31)14-6-4-3-5-7-14/h3-11,13,19,31H,12H2,1-2H3,(H2,25,27,28,29)/t19-/m1/s1
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| Chemical Name |
5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(1,3,4-oxadiazol-2-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one
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| Synonyms |
HPK1-IN-7 ; HPK1-IN 7, HPK1-IN7
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~125.0 mg/mL (~272.7 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1812 mL | 10.9058 mL | 21.8117 mL | |
| 5 mM | 0.4362 mL | 2.1812 mL | 4.3623 mL | |
| 10 mM | 0.2181 mL | 1.0906 mL | 2.1812 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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